U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Renal cyst

MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
Synonym: Cystic kidney disease
SNOMED CT: Cyst of kidney (722223000); Renal cyst (722223000)
 
HPO: HP:0000107
Monarch Initiative: MONDO:0002473

Definition

A fluid filled sac in the kidney. [from HPO]

Conditions with this feature

Smith-Lemli-Opitz syndrome
MedGen UID:
61231
Concept ID:
C0175694
Disease or Syndrome
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple-anomaly / cognitive impairment syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth restriction, microcephaly, moderate-to-severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide; individuals with normal development and only minor malformations have been described.
Fryns syndrome
MedGen UID:
65088
Concept ID:
C0220730
Disease or Syndrome
Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia, or agenesis); characteristic facial appearance (coarse facies, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw); short distal phalanges of the fingers and toes (the nails may also be small); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia / renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, and/or genitalia). Survival beyond the neonatal period is rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common.
Pallister-Hall syndrome
MedGen UID:
120514
Concept ID:
C0265220
Disease or Syndrome
GLI3-related Pallister-Hall syndrome (GLI3-PHS) is characterized by a spectrum of anomalies ranging from polydactyly, asymptomatic bifid epiglottis, and hypothalamic hamartoma at the mild end to laryngotracheal cleft with neonatal lethality at the severe end. Individuals with mild GLI3-PHS may be incorrectly diagnosed as having isolated postaxial polydactyly type A. Individuals with GLI3-PHS can have pituitary insufficiency and may die as neonates from undiagnosed and untreated adrenal insufficiency.
Cerebro-costo-mandibular syndrome
MedGen UID:
120537
Concept ID:
C0265342
Disease or Syndrome
Cerebrocostomandibular syndrome (CCMS) is a rare autosomal dominant disorder characterized by branchial arch-derivative and thoracic malformations. A key craniofacial characteristic is micrognathia, often associated with cleft palate and feeding and airway difficulties. Patients with CCMS have a narrow chest and striking posterior rib gaps which distinguish this condition (summary by Tooley et al., 2016). See CDG2G (611209) for a cerebrocostomandibular-like syndrome.
Pallister-Killian syndrome
MedGen UID:
120540
Concept ID:
C0265449
Disease or Syndrome
Pallister-Killian syndrome (PKS) is a dysmorphic condition involving most organ systems, but is also characterized by a tissue-limited mosaicism; most fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. The extra metacentric chromosome is an isochromosome for part of the short arm of chromosome 12: i(12)(p10) (Peltomaki et al., 1987; Warburton et al., 1987).
Peroxisome biogenesis disorder 1B
MedGen UID:
79470
Concept ID:
C0282527
Disease or Syndrome
Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term "ZSD" is now used to refer to all individuals with a defect in one of the ZSD-PEX genes regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and the long bones), and liver disease that can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss), neurologic involvement (ataxia, polyneuropathy, and leukodystrophy), liver dysfunction, adrenal insufficiency, and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.
Bifunctional peroxisomal enzyme deficiency
MedGen UID:
137982
Concept ID:
C0342870
Pathologic Function
D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed.
PMM2-congenital disorder of glycosylation
MedGen UID:
138111
Concept ID:
C0349653
Disease or Syndrome
PMM2-CDG, the most common of a group of disorders of abnormal glycosylation of N-linked oligosaccharides, is divided into three clinical stages: infantile multisystem, late-infantile and childhood ataxia–intellectual disability, and adult stable disability. The clinical manifestations and course are highly variable, ranging from infants who die in the first year of life to mildly affected adults. Clinical findings tend to be similar in sibs. In the infantile multisystem presentation, infants show axial hypotonia, hyporeflexia, esotropia, and developmental delay. Feeding problems, vomiting, faltering growth, and developmental delay are frequently seen. Subcutaneous fat may be excessive over the buttocks and suprapubic region. Two distinct clinical courses are observed: (1) a nonfatal neurologic course with faltering growth, strabismus, developmental delay, cerebellar hypoplasia, and hepatopathy in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade; and (2) a more severe neurologic-multivisceral course with approximately 20% mortality in the first year of life. The late-infantile and childhood ataxia–intellectual disability stage, which begins between ages three and ten years, is characterized by hypotonia, ataxia, severely delayed language and motor development, inability to walk, and IQ of 40 to 70; other findings include seizures, stroke-like episodes or transient unilateral loss of function, coagulopathy, retinitis pigmentosa, joint contractures, and skeletal deformities. In the adult stable disability stage, intellectual ability is stable; peripheral neuropathy is variable, progressive retinitis pigmentosa and myopia are seen, thoracic and spinal deformities with osteoporosis worsen, and premature aging is observed; females may lack secondary sexual development and males may exhibit decreased testicular volume. Hypogonadotropic hypogonadism and coagulopathy may occur. The risk for deep venous thrombosis is increased.
Branchiooculofacial syndrome
MedGen UID:
91261
Concept ID:
C0376524
Disease or Syndrome
The branchiooculofacial syndrome (BOFS) is characterized by: branchial (cervical or infra- or supra-auricular) skin defects that range from barely perceptible thin skin or hair patch to erythematous "hemangiomatous" lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include ocular hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called "pseudocleft lip") with or without cleft palate, upper lip pits, and lower facial weakness (asymmetric crying face or partial 7th cranial nerve weakness). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.
Renal cysts and diabetes syndrome
MedGen UID:
96569
Concept ID:
C0431693
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Kleefstra syndrome 1
MedGen UID:
208639
Concept ID:
C0795833
Disease or Syndrome
Kleefstra syndrome is characterized by intellectual disability, autistic-like features, childhood hypotonia, and distinctive facial features. The majority of individuals function in the moderate-to-severe spectrum of intellectual disability although a few individuals have mild delay and total IQ within low-normal range. While most have severe expressive speech delay with little speech development, general language development is usually at a higher level, making nonverbal communication possible. A complex pattern of other findings can also be observed; these include heart defects, renal/urologic defects, genital defects in males, severe respiratory infections, epilepsy / febrile seizures, psychiatric disorders, and extreme apathy or catatonic-like features after puberty.
Simpson-Golabi-Behmel syndrome type 1
MedGen UID:
162917
Concept ID:
C0796154
Disease or Syndrome
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is characterized by pre- and postnatal macrosomia; distinctive craniofacial features (including macrocephaly, coarse facial features, macrostomia, macroglossia, and palatal abnormalities); and commonly, mild-to-severe intellectual disability with or without structural brain anomalies. Other variable findings include supernumerary nipples, diastasis recti / umbilical hernia, congenital heart defects, diaphragmatic hernia, genitourinary defects, and gastrointestinal anomalies. Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. Affected individuals are at increased risk for embryonal tumors including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma, and medulloblastoma.
Polycystic liver disease 1
MedGen UID:
165781
Concept ID:
C0887850
Congenital Abnormality
Polycystic liver disease-1 is an autosomal dominant condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Although the clinical presentation and histologic features of polycystic liver disease in the presence or absence of autosomal dominant polycystic kidney disease (see, e.g., PKD1, 173900) are indistinguishable, PCLD1 is a genetically distinct form of isolated polycystic liver disease (summary by Reynolds et al., 2000). A subset of patients (28-35%) may develop kidney cysts that are usually incidental findings and do not result in clinically significant renal disease (review by Cnossen and Drenth, 2014). Genetic Heterogeneity of Polycystic Liver Disease See also PCLD2 (617004), caused by mutation in the SEC63 gene (608648) on chromosome 6q21; PCLD3 (617874), caused by mutation in the ALG8 gene (608103) on chromosome 11p; and PCLD4 (617875), causes by mutation in the LRP5 gene (603506) on chromosome 11q13.
Hajdu-Cheney syndrome
MedGen UID:
182961
Concept ID:
C0917715
Disease or Syndrome
Hajdu-Cheney syndrome (HJCYS) is a rare autosomal dominant skeletal disorder characterized by short stature, coarse and dysmorphic facies, bowing of the long bones, and vertebral anomalies. Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. There is progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. Additional and variable features include hearing loss, renal cysts, and cardiovascular anomalies (summary by Ramos et al., 1998; Simpson et al., 2011; Isidor et al., 2011).
Joubert syndrome 2
MedGen UID:
334114
Concept ID:
C1842577
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Spondylocarpotarsal synostosis syndrome
MedGen UID:
341339
Concept ID:
C1848934
Disease or Syndrome
The FLNB disorders include a spectrum of phenotypes ranging from mild to severe. At the mild end are spondylocarpotarsal synostosis (SCT) syndrome and Larsen syndrome; at the severe end are the phenotypic continuum of atelosteogenesis types I (AOI) and III (AOIII) and Piepkorn osteochondrodysplasia (POCD). SCT syndrome is characterized by postnatal disproportionate short stature, scoliosis and lordosis, clubfeet, hearing loss, dental enamel hypoplasia, carpal and tarsal synostosis, and vertebral fusions. Larsen syndrome is characterized by congenital dislocations of the hip, knee, and elbow; clubfeet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy; short, broad, spatulate distal phalanges; distinctive craniofacies (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes); vertebral anomalies; and supernumerary carpal and tarsal bone ossification centers. Individuals with SCT syndrome and Larsen syndrome can have midline cleft palate and hearing loss. AOI and AOIII are characterized by severe short-limbed dwarfism; dislocated hips, knees, and elbows; and clubfeet. AOI is lethal in the perinatal period. In individuals with AOIII, survival beyond the neonatal period is possible with intensive and invasive respiratory support. Piepkorn osteochondrodysplasia (POCD) is a perinatal-lethal micromelic dwarfism characterized by flipper-like limbs (polysyndactyly with complete syndactyly of all fingers and toes, hypoplastic or absent first digits, and duplicated intermediate and distal phalanges), macrobrachycephaly, prominant forehead, hypertelorism, and exophthalmos. Occasional features include cleft palate, omphalocele, and cardiac and genitourinary anomalies. The radiographic features at mid-gestation are characteristic.
Saldino-Mainzer syndrome
MedGen UID:
341455
Concept ID:
C1849437
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Polysyndactyly-cardiac malformation syndrome
MedGen UID:
337895
Concept ID:
C1849719
Congenital Abnormality
Syndrome with characteristics of polysyndactyly, hexadactyly (duplication of the first toe) and complex cardiac malformation (including atrial and ventricular septal defect, single ventricle, aortic dextroposition, or dilation of the right heart). It has been described in six patients from three unrelated families. Other manifestations were present in some patients (i.e. facial dysmorphism, hepatic cysts).
Mosaic variegated aneuploidy syndrome 1
MedGen UID:
338026
Concept ID:
C1850343
Disease or Syndrome
Mosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes, a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism. Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.\n\nIn MVA syndrome, growth before birth is slow (intrauterine growth restriction). After birth, affected individuals continue to grow at a slow rate and are shorter than average. In addition, they typically have an unusually small head size (microcephaly). Another common feature of MVA syndrome is an increased risk of developing cancer in childhood. Cancers that occur most frequently in affected individuals include a cancer of muscle tissue called rhabdomyosarcoma, a form of kidney cancer known as Wilms tumor, and a cancer of the blood-forming tissue known as leukemia.\n\nLess commonly, people with MVA syndrome have eye abnormalities or distinctive facial features, such as a broad nasal bridge and low-set ears. Some affected individuals have brain abnormalities, the most common of which is called Dandy-Walker malformation. Intellectual disability, seizures, and other health problems can also occur in people with MVA syndrome.\n\nThere are at least three types of MVA syndrome, each with a different genetic cause. Type 1 is the most common and displays the classic signs and symptoms described above. Type 2 appears to have slightly different signs and symptoms than type 1, although the small number of affected individuals makes it difficult to define its characteristic features. Individuals with MVA syndrome type 2 grow slowly before and after birth; however, their head size is typically normal. Some people with MVA syndrome type 2 have unusually short arms. Individuals with MVA syndrome type 2 do not seem to have an increased risk of cancer. Another form of MVA syndrome is characterized by a high risk of developing Wilms tumor. Individuals with this form may also have other signs and symptoms typical of MVA syndrome type 1.
Renal coloboma syndrome
MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis.
Tuberous sclerosis 1
MedGen UID:
344288
Concept ID:
C1854465
Disease or Syndrome
Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical tubers, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.
Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome
MedGen UID:
381579
Concept ID:
C1855188
Disease or Syndrome
Retinitis pigmentosa with or without skeletal anomalies (RPSKA) is characterized by retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurologic defects. Night blindness occurs around 10 years of age, followed by restriction of visual fields. Brachydactyly affects primarily the distal phalanges. Craniofacial abnormalities include frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears (summary by Xu et al., 2017).
Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome
MedGen UID:
343465
Concept ID:
C1856053
Disease or Syndrome
MARCH is an autosomal recessive lethal congenital disorder characterized by severe hydranencephaly with almost complete absence of the cerebral hemispheres, which are replaced by fluid, relative preservation of the posterior fossa structures, and renal dysplasia or agenesis. Affected fetuses either die in utero or shortly after birth, and show arthrogryposis and features consistent with anhydramnios. Histologic examination of residual brain tissue shows multinucleated neurons resulting from impaired cytokinesis (summary by Frosk et al., 2017).
Genito-palato-cardiac syndrome
MedGen UID:
341558
Concept ID:
C1856466
Disease or Syndrome
A rare multiple congenital anomalies/dysmorphic syndrome with characteristics of male, 46,XY gonadal dysgenesis, cleft palate, micrognathia, conotruncal heart defects and unspecific skeletal, brain and kidney anomalies.
Alagille syndrome due to a NOTCH2 point mutation
MedGen UID:
341844
Concept ID:
C1857761
Disease or Syndrome
Alagille syndrome (ALGS) is a multisystem disorder with a wide spectrum of clinical variability; this variability is seen even among individuals from the same family. The major clinical manifestations of ALGS are bile duct paucity on liver biopsy, cholestasis, congenital cardiac defects (primarily involving the pulmonary arteries), butterfly vertebrae, ophthalmologic abnormalities (most commonly posterior embryotoxon), and characteristic facial features. Renal abnormalities, growth failure, developmental delays, splenomegaly, and vascular abnormalities may also occur.
Neonatal diabetes mellitus with congenital hypothyroidism
MedGen UID:
347541
Concept ID:
C1857775
Disease or Syndrome
Neonatal diabetes mellitus with congenital hypothyroidism (NDH) syndrome is characterized by intrauterine growth retardation and onset of nonimmune diabetes mellitus within the first few weeks of life. Other features include renal parenchymal disease, primarily renal cystic dysplasia, and hepatic disease, with hepatitis in some patients and hepatic fibrosis and cirrhosis in others. Facial dysmorphism, when present, consistently involves low-set ears, epicanthal folds, flat nasal bridge, long philtrum, and thin upper lip. Most patients exhibit developmental delay (Dimitri et al., 2015).
Bardet-Biedl syndrome 6
MedGen UID:
347610
Concept ID:
C1858054
Disease or Syndrome
Bardet-Biedl syndrome-6 (BBS6) is an autosomal recessive disorder with the cardinal features of postaxial polydactyly, retinitis pigmentosa, kidney defects, obesity, and mental retardation (Slavotinek et al., 2000). Zaghloul and Katsanis (2009) estimated that mutations in the MKKS gene account for 5.8% of the total BBS mutational load. For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Osteodysplastic primordial dwarfism, type 1
MedGen UID:
347149
Concept ID:
C1859452
Congenital Abnormality
Microcephalic osteodysplastic primordial dwarfism type I (MOPD1) is a severe autosomal recessive skeletal dysplasia characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular/auditory sensory deficits. Patients often die in early childhood (summary by Pierce and Morse, 2012).
Bardet-Biedl syndrome 10
MedGen UID:
347909
Concept ID:
C1859568
Disease or Syndrome
BBS10 is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia (Stoetzel et al., 2006). BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients (Stoetzel et al., 2006; Zaghloul and Katsanis, 2009). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Tuberous sclerosis 2
MedGen UID:
348170
Concept ID:
C1860707
Disease or Syndrome
Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical tubers, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.
Axial osteomalacia
MedGen UID:
354730
Concept ID:
C1862372
Disease or Syndrome
Meckel syndrome, type 2
MedGen UID:
351059
Concept ID:
C1864148
Disease or Syndrome
Meckel syndrome is a rare autosomal recessive lethal condition characterized by an occipital meningoencephalocele, enlarged kidneys with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and postaxial polydactyly. For a more complete phenotypic description and information on genetic heterogeneity, see MKS1 (249000).
MPI-congenital disorder of glycosylation
MedGen UID:
400692
Concept ID:
C1865145
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
Meckel syndrome, type 5
MedGen UID:
409740
Concept ID:
C1969052
Disease or Syndrome
Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.\n\nOther signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.\n\nBecause of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.
Joubert syndrome 7
MedGen UID:
369401
Concept ID:
C1969053
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Meckel syndrome, type 4
MedGen UID:
410003
Concept ID:
C1970161
Disease or Syndrome
Meckel syndrome is an autosomal recessive pre- or perinatal lethal disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Baala et al., 2007). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
MedGen UID:
382033
Concept ID:
C2673195
Disease or Syndrome
The spectrum of COL4A1-related disorders includes: small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (retinal arterial tortuosity, Axenfeld-Rieger anomaly, cataract) and systemic findings (kidney involvement, muscle cramps, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia). On imaging studies, small-vessel brain disease is manifest as diffuse periventricular leukoencephalopathy, lacunar infarcts, microhemorrhage, dilated perivascular spaces, and deep intracerebral hemorrhages. Clinically, small-vessel brain disease manifests as infantile hemiparesis, seizures, single or recurrent hemorrhagic stroke, ischemic stroke, and isolated migraine with aura. Porencephaly (fluid-filled cavities in the brain detected by CT or MRI) is typically manifest as infantile hemiparesis, seizures, and intellectual disability; however, on occasion it can be an incidental finding. HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome usually associates asymptomatic small-vessel brain disease, cerebral large vessel involvement (i.e., aneurysms), and systemic findings involving the kidney, muscle, and small vessels of the eye. Two additional phenotypes include isolated retinal artery tortuosity and nonsyndromic autosomal dominant congenital cataract.
Meckel syndrome, type 6
MedGen UID:
382942
Concept ID:
C2676790
Disease or Syndrome
Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.\n\nOther signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.\n\nMeckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.
Bardet-Biedl syndrome 4
MedGen UID:
423627
Concept ID:
C2936864
Disease or Syndrome
BBS4 is a rare multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction that accounts for less than 3% of BBS (Katsanis et al., 2002). Anosmia has been described in patients with BBS4 (Iannaccone et al., 2005), as well as polydactyly confined to the hands (Carmi et al., 1995). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Fanconi anemia complementation group O
MedGen UID:
462003
Concept ID:
C3150653
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.
Cranioectodermal dysplasia 2
MedGen UID:
462224
Concept ID:
C3150874
Disease or Syndrome
Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Short-rib thoracic dysplasia 7 with or without polydactyly
MedGen UID:
481422
Concept ID:
C3279792
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Meckel syndrome, type 10
MedGen UID:
481666
Concept ID:
C3280036
Disease or Syndrome
Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.\n\nOther signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.\n\nBecause of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.
Joubert syndrome 14
MedGen UID:
482396
Concept ID:
C3280766
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Joubert syndrome 16
MedGen UID:
482536
Concept ID:
C3280906
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Joubert syndrome 18
MedGen UID:
766672
Concept ID:
C3553758
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Peroxisome biogenesis disorder 4A (Zellweger)
MedGen UID:
766850
Concept ID:
C3553936
Disease or Syndrome
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 4 (CG4, equivalent to CG6 and CGC) have mutations in the PEX6 gene. For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 5A (Zellweger)
MedGen UID:
766854
Concept ID:
C3553940
Disease or Syndrome
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 5 (CG5, equivalent to CG10 and CGF) have mutations in the PEX2 gene. For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 6A (Zellweger)
MedGen UID:
766861
Concept ID:
C3553947
Disease or Syndrome
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 7 (CG7, equivalent to CGB) have mutations in the PEX10 gene. For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 11A (Zellweger)
MedGen UID:
766914
Concept ID:
C3554000
Disease or Syndrome
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 13 (CG13, equivalent to CGH) have mutations in the PEX13 gene. For information on the history of PBD complementation groups, see 214100.
Joubert syndrome 20
MedGen UID:
767149
Concept ID:
C3554235
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Bardet-Biedl syndrome 17
MedGen UID:
811538
Concept ID:
C3714980
Disease or Syndrome
Bardet-Biedl syndrome-17 (BBS17) is an autosomal recessive ciliopathy characterized by retinitis pigmentosa, cognitive impairment, obesity, renal dysfunction, and hypogenitalism. Polydactyly, most often postaxial, is also a primary feature of BBS; in BBS17, mesoaxial polydactyly, with fused or Y-shaped metacarpals, is a distinct manifestation (Deffert et al., 2007; Schaefer et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Multiple congenital anomalies-hypotonia-seizures syndrome 3
MedGen UID:
815686
Concept ID:
C3809356
Disease or Syndrome
Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age (summary by Maydan et al., 2011). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
8q24.3 microdeletion syndrome
MedGen UID:
816353
Concept ID:
C3810023
Disease or Syndrome
Verheij syndrome is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects (summary by Verheij et al., 2009 and Dauber et al., 2013).
Joubert syndrome 21
MedGen UID:
816542
Concept ID:
C3810212
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Bardet-Biedl syndrome 16
MedGen UID:
855172
Concept ID:
C3889474
Disease or Syndrome
Bardet-Biedl syndrome-16 (BBS16) is an autosomal recessive ciliopathy characterized by retinal degeneration, obesity, renal disease, and cognitive impairment. Although polydactyly is considered a primary feature of BBS overall, it has not been reported in any BBS16 patient (Billingsley et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Short-rib thoracic dysplasia 13 with or without polydactyly
MedGen UID:
898712
Concept ID:
C4225378
Disease or Syndrome
An asphyxiating thoracic dystrophy that has material basis in homozygous mutation in the CEP120 gene on chromosome 5q23.
Nephronophthisis 20
MedGen UID:
934607
Concept ID:
C4310640
Disease or Syndrome
Nephronophthisis-20 (NPHP20) is an autosomal recessive tubulointerstitial nephritis characterized by progressive renal fibrosis resulting in end-stage renal failure. The age at onset is relatively late compared to other forms of NPHP, and patients develop end-stage renal disease in the second or third decades. Unlike most other forms of NPHP, NPHP20 does not have features of a ciliopathy and patients do not appear to have extrarenal manifestations (summary by Macia et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies
MedGen UID:
934611
Concept ID:
C4310644
Disease or Syndrome
GDACCF is an intellectual disability syndrome apparent soon after birth with neonatal hypotonia, poor feeding, and respiratory insufficiency followed by delayed psychomotor development and intellectual disability with poor speech. Brain imaging shows aplasia or hypoplasia of the corpus callosum. Affected individuals have variable dysmorphic facial features, and some may have dysplastic, cystic kidneys or mild cardiac defects (summary by Stevens et al., 2016).
Tall stature-intellectual disability-renal anomalies syndrome
MedGen UID:
934682
Concept ID:
C4310715
Disease or Syndrome
Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor (summary by Akawi et al., 2016).
Familial adenomatous polyposis 4
MedGen UID:
934686
Concept ID:
C4310719
Disease or Syndrome
Familial adenomatous polyposis-4 is an autosomal recessive tumor predisposition syndrome characterized by the development of multiple colonic adenomas in adulthood, often with progression to colorectal cancer. Proliferative lesions in other tissues may also occur (summary by Adam et al., 2016). For a discussion of genetic heterogeneity of familial adenomatous polyposis, see FAP1 (175100).
Hyperuricemic nephropathy, familial juvenile type 4
MedGen UID:
934708
Concept ID:
C4310741
Disease or Syndrome
Autosomal dominant tubulointerstitial kidney disease-5 (ADTKD5) is characterized by the onset of progressive chronic renal disease in the first decades of life. Mild hyperuricemia may be present, but gout, hypertension, and proteinuria are usually absent. The disease may be associated with anemia or neutropenia. Some patients may have additional findings, including poor overall growth and impaired cognitive function. Renal biopsy shows tubulointerstitial abnormalities with atrophic tubules and fibrosis; secondary glomerular abnormalities and simple cysts may also be present (summary by Bolar et al., 2016). For a discussion of genetic heterogeneity and revised nomenclature of ADTKD, see ADTKD1 (162000).
Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart
MedGen UID:
934739
Concept ID:
C4310772
Disease or Syndrome
RERE-related disorders are characterized by neurodevelopmental problems with or without structural anomalies of the eyes, heart, kidneys, and genitourinary tract and mild sensorineural hearing loss. Hypotonia and feeding problems are common among affected individuals. Developmental delay and intellectual disability range from mild to profound. Behavior problems may include attention-deficit/hyperactivity disorder, self-injurious behavior, and autism spectrum disorder. A variety of eye anomalies (coloboma, optic nerve anomalies, microphthalmia, and/or Peter's anomaly) and vision issues (myopia, anisometropia, astigmatism, exotropia, esotropia) have been reported. Congenital heart defects, most commonly septal defects, have also been described. Genitourinary abnormalities include vesicoureteral reflux, and cryptorchidism and hypospadias in males. Sensorineural hearing loss can be unilateral or bilateral.
Structural heart defects and renal anomalies syndrome
MedGen UID:
1387412
Concept ID:
C4479549
Disease or Syndrome
Polycystic kidney disease 4
MedGen UID:
1621793
Concept ID:
C4540575
Disease or Syndrome
Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.
Familial juvenile hyperuricemic nephropathy type 1
MedGen UID:
1645893
Concept ID:
C4551496
Disease or Syndrome
Autosomal dominant tubulointerstitial kidney disease – UMOD (ADTKD-UMOD) is characterized by normal urinalysis and slowly progressive chronic kidney disease (CKD), usually first noted in the teen years and progressing to end-stage renal disease (ESRD) between the third and seventh decades. Hyperuricemia is often present from an early age, and gout (resulting from reduced kidney excretion of uric acid) occurs in the teenage years in about 8% of affected individuals and develops in 55% of affected individuals over time.
Joubert syndrome 1
MedGen UID:
1644883
Concept ID:
C4551568
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Cornelia de Lange syndrome 1
MedGen UID:
1645760
Concept ID:
C4551851
Disease or Syndrome
Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe. Severe (classic) CdLS is characterized by distinctive facial features, growth restriction (prenatal onset; <5th centile throughout life), hypertrichosis, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched and/or thick eyebrows, long eyelashes, short nasal bridge with anteverted nares, small widely spaced teeth, and microcephaly. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS. Across the CdLS spectrum IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Other frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia.
Asphyxiating thoracic dystrophy 1
MedGen UID:
1648057
Concept ID:
C4551856
Congenital Abnormality
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). Genetic Heterogeneity of Asphyxiating Thoracic Dysplasia SRTD1 has been mapped to chromosome 15q13. See also SRTD2 (611263), caused by mutation in the IFT80 gene (611177); SRTD3 (613091), caused by mutation in the DYNC2H1 gene (603297); SRTD4 (613819), caused by mutation in the TTC21B gene (612014); SRTD5 (614376), caused by mutation in the WDR19 gene (608151); SRTD6 (263520), caused by mutation in the NEK1 gene (604588); SRTD7 (614091), caused by mutation in the WDR35 gene (613602); SRTD8 (615503), caused by mutation in the WDR60 gene (615462); SRTD9 (266920), caused by mutation in the IFT140 gene (614620); SRTD10 (615630), caused by mutation in the IFT172 gene (607386); SRTD11 (615633), caused by mutation in the WDR34 gene (613363); SRTD13 (616300), caused by mutation in the CEP120 gene (613446); SRTD14 (616546), caused by mutation in the KIAA0586 gene (610178); SRTD15 (617088), caused by mutation in the DYNC2LI1 gene (617083); SRTD16 (617102), caused by mutation in the IFT52 gene (617094); SRTD17 (617405), caused by mutation in the TCTEX1D2 gene (617353); SRTD18 (617866), caused by mutation in the IFT43 gene (614068); SRTD19 (617895), caused by mutation in the IFT81 gene (605489); SRTD20 (617925), caused by mutation in the INTU gene (610621); and SRTD21 (619479), caused by mutation in the KIAA0753 gene (617112). See also SRTD12 (Beemer-Langer syndrome; 269860).
Polycystic liver disease 3 with or without kidney cysts
MedGen UID:
1646969
Concept ID:
C4693472
Disease or Syndrome
PCLD3 is an autosomal dominant disorder characterized by the development of multiple liver cysts that usually becomes apparent in adulthood. Liver cysts range in size and number, and the clinical severity is variable. Most patients also have a few renal cysts, but they do not result in significant renal disease or renal failure (summary by Besse et al., 2017). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050).
Polycystic liver disease 4 with or without kidney cysts
MedGen UID:
1644991
Concept ID:
C4693479
Disease or Syndrome
PCLD4 is an autosomal dominant disease characterized by adult-onset of liver cysts arising from the bile duct epithelium. Some patients may develop a few kidney cysts, but these are often incidental and do not result in renal failure (summary by Cnossen et al., 2014). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050).
Combined oxidative phosphorylation defect type 11
MedGen UID:
1682397
Concept ID:
C5190991
Disease or Syndrome
Combined oxidative phosphorylation deficiency-21 (COXPD11) is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes (summary by Garcia-Diaz et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Developmental delay with or without dysmorphic facies and autism
MedGen UID:
1679263
Concept ID:
C5193106
Disease or Syndrome
Developmental delay with or without dysmorphic facies and autism (DEDDFA) is a complex neurodevelopmental disorder apparent from infancy or early childhood and associated with variably impaired intellectual development. Some patients may be severely affected with no speech and inability to walk, whereas others may be able to attend special schools or have normal intellectual function associated with autism spectrum disorder and mild speech delay. Genetic analysis has suggested that the phenotype can be broadly categorized into 2 main groups. Patients with TRRAP mutations affecting residues 1031-1159 have a more severe disorder, often with multisystem involvement, including renal, cardiac, and genitourinary systems, as well as structural brain abnormalities. Patients with mutations outside of that region tend to have a less severe phenotype with a higher incidence of autism and usually no systemic involvement. Patients in both groups usually have somewhat similar dysmorphic facial features, such as upslanting palpebral fissures, hypertelorism, low-set ears, and broad or depressed nasal bridge, although these features are highly variable (summary by Cogne et al., 2019).
Khan-Khan-Katsanis syndrome
MedGen UID:
1682553
Concept ID:
C5193110
Disease or Syndrome
Khan-Khan-Katsanis syndrome (3KS) is an autosomal recessive neurodevelopmental disorder with variable involvement of the ocular, renal, skeletal, and sometimes cardiac systems. Affected individuals present at birth with multiple congenital anomalies, defects in urogenital and limb morphogenesis, poor overall growth with microcephaly, and global developmental delay (summary by Khan et al., 2019).
COACH syndrome 1
MedGen UID:
1769861
Concept ID:
C5435651
Disease or Syndrome
Any COACH syndrome in which the cause of the disease is a variation in the TMEM67 gene.
Otofaciocervical syndrome 2
MedGen UID:
1782278
Concept ID:
C5442121
Disease or Syndrome
Otofaciocervical syndrome-2 with T-cell deficiency (OTFCS2) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability (summary by Pohl et al., 2013). Patients have been reported who also exhibit altered thymus development with T-cell immunodeficiency and recurrent, sometimes fatal, infections (Paganini et al., 2017; Yamazaki et al., 2020). For a discussion of genetic heterogeneity of otofaciocervical syndrome, see OTFCS1 (166780).
Mayer Rokitansky Kuster Hauser syndrome type 1
MedGen UID:
1797978
Concept ID:
C5566555
Disease or Syndrome
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by uterovaginal atresia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total mullerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5,000 newborn girls (Cheroki et al., 2006). The abnormality of sexual development in MRKH syndrome is the same as that in the MURCS association (601076), in which cervicothoracic somite anomalies, unilateral renal agenesis, and conductive deafness are also seen. Mullerian aplasia and hyperandrogenism (158330) is caused by mutation in the WNT4 gene (603490). Familial cases of unilateral or bilateral renal agenesis in combination with mullerian anomalies have also been reported (see urogenital adysplasia, 191830).
Hepatorenocardiac degenerative fibrosis
MedGen UID:
1808950
Concept ID:
C5676996
Disease or Syndrome
Hepatorenocardiac degenerative fibrosis (HRCDF) is a primarily fibrotic disease affecting the liver, kidney, and heart, with considerable variability in disease onset and expression. Affected individuals develop degenerative hepatic fibrosis in childhood or early adulthood, with variable later onset of fibrocystic kidney disease and hypertrophic cardiomyopathy (Devane et al., 2022).
Intellectual developmental disorder, X-linked 112
MedGen UID:
1840225
Concept ID:
C5829589
Disease or Syndrome
X-linked intellectual disorder-112 (XLID112) is a neurodevelopmental disorder characterized by developmental delay, with speech delay more prominent than motor delay, autism or autism traits, and variable dysmorphic features. Affected females have been reported, which appears to be related to skewed X-inactivation (summary by Hiatt et al., 2023).
Birt-Hogg-Dube syndrome 1
MedGen UID:
1051978
Concept ID:
CN375946
Disease or Syndrome
Any Birt-Hogg-Dube (BHD) syndrome in which the cause of the disease is a variation in the FLCN gene.

Professional guidelines

PubMed

Tay SY, Tiu CM, Hu B, Wang HK, Chiou HJ, Lin YH, Lai YC, Chan WP, Chou YH
J Chin Med Assoc 2018 Dec;81(12):1017-1026. Epub 2018 Jul 13 doi: 10.1016/j.jcma.2018.04.008. PMID: 30017809
Bas O, Nalbant I, Can Sener N, Firat H, Yeşil S, Zengin K, Yalcınkaya F, Imamoglu A
JSLS 2015 Jan-Mar;19(1):e2014.00097. doi: 10.4293/JSLS.2014.00097. PMID: 25848184Free PMC Article
Lantinga MA, Drenth JP, Gevers TJ
Nephrol Dial Transplant 2015 May;30(5):744-51. Epub 2014 Jun 20 doi: 10.1093/ndt/gfu227. PMID: 24950937

Recent clinical studies

Therapy

Zhu M, Chu X, Liu C
Arch Iran Med 2022 Mar 1;25(3):155-160. doi: 10.34172/aim.2022.26. PMID: 35429956
Kazmierski B, Deurdulian C, Tchelepi H, Grant EG
Abdom Radiol (NY) 2018 Apr;43(4):880-898. doi: 10.1007/s00261-017-1307-0. PMID: 28856401
Ghata J, Cowley BD Jr
Compr Physiol 2017 Jun 18;7(3):945-975. doi: 10.1002/cphy.c160018. PMID: 28640449
Rangan GK, Tchan MC, Tong A, Wong AT, Nankivell BJ
Intern Med J 2016 Aug;46(8):883-92. doi: 10.1111/imj.13143. PMID: 27553994
Rini BI, Rathmell WK, Godley P
Curr Opin Oncol 2008 May;20(3):300-6. doi: 10.1097/CCO.0b013e3282f9782b. PMID: 18391630

Prognosis

Verbitsky M, Krishnamurthy S, Krithivasan P, Hughes D, Khan A, Marasà M, Vena N, Khosla P, Zhang J, Lim TY, Glessner JT, Weng C, Shang N, Shen Y, Hripcsak G, Hakonarson H, Ionita-Laza I, Levy B, Kenny EE, Loos RJF, Kiryluk K, Sanna-Cherchi S, Crosslin DR, Furth S, Warady BA, Igo RP Jr, Iyengar SK, Wong CS, Parsa A, Feldman HI, Gharavi AG
J Am Soc Nephrol 2023 Apr 1;34(4):607-618. Epub 2022 Oct 27 doi: 10.1681/ASN.2022060725. PMID: 36302597Free PMC Article
Chen J, Ma X, Xu D, Cao W, Kong X
Ren Fail 2019 Nov;41(1):600-606. doi: 10.1080/0886022X.2019.1632718. PMID: 31282239Free PMC Article
Kwon T, Lim B, You D, Hong B, Hong JH, Kim CS, Jeong IG
Nephrology (Carlton) 2016 Aug;21(8):687-92. doi: 10.1111/nep.12654. PMID: 26481869
Verghese P, Miyashita Y
Clin Perinatol 2014 Sep;41(3):543-60. Epub 2014 Jul 19 doi: 10.1016/j.clp.2014.05.005. PMID: 25155726
Rini BI, Rathmell WK, Godley P
Curr Opin Oncol 2008 May;20(3):300-6. doi: 10.1097/CCO.0b013e3282f9782b. PMID: 18391630

Clinical prediction guides

Verbitsky M, Krishnamurthy S, Krithivasan P, Hughes D, Khan A, Marasà M, Vena N, Khosla P, Zhang J, Lim TY, Glessner JT, Weng C, Shang N, Shen Y, Hripcsak G, Hakonarson H, Ionita-Laza I, Levy B, Kenny EE, Loos RJF, Kiryluk K, Sanna-Cherchi S, Crosslin DR, Furth S, Warady BA, Igo RP Jr, Iyengar SK, Wong CS, Parsa A, Feldman HI, Gharavi AG
J Am Soc Nephrol 2023 Apr 1;34(4):607-618. Epub 2022 Oct 27 doi: 10.1681/ASN.2022060725. PMID: 36302597Free PMC Article
Zhu M, Chu X, Liu C
Arch Iran Med 2022 Mar 1;25(3):155-160. doi: 10.34172/aim.2022.26. PMID: 35429956
Zhang Y, Reif G, Wallace DP
Cell Signal 2020 Aug;72:109646. Epub 2020 Apr 18 doi: 10.1016/j.cellsig.2020.109646. PMID: 32311505Free PMC Article
Rangan GK, Lopez-Vargas P, Nankivell BJ, Tchan M, Tong A, Tunnicliffe DJ, Savige J
Semin Nephrol 2015 Nov;35(6):524-37. doi: 10.1016/j.semnephrol.2015.10.002. PMID: 26718155
Singh AD, Shields CL, Shields JA
Surv Ophthalmol 2001 Sep-Oct;46(2):117-42. doi: 10.1016/s0039-6257(01)00245-4. PMID: 11578646

Recent systematic reviews

Brown D, Nalagatla S, Stonier T, Tsampoukas G, Al-Ansari A, Amer T, Aboumarzouk OM
Abdom Radiol (NY) 2021 Jun;46(6):2875-2890. Epub 2021 Feb 5 doi: 10.1007/s00261-021-02953-9. PMID: 33544165
Chewcharat A, Hamaya R, Thongprayoon C, Cato LD, Mao MA, Cheungpasitporn W
J Evid Based Med 2020 Nov;13(4):265-274. Epub 2020 May 25 doi: 10.1111/jebm.12385. PMID: 32452169
Lantinga MA, Casteleijn NF, Geudens A, de Sévaux RG, van Assen S, Leliveld AM, Gansevoort RT, Drenth JP; DIPAK Consortium
Nephrol Dial Transplant 2017 Jan 1;32(1):144-150. doi: 10.1093/ndt/gfv452. PMID: 26908766
Woon C, Bielinski-Bradbury A, O'Reilly K, Robinson P
BMC Nephrol 2015 Aug 15;16:140. doi: 10.1186/s12882-015-0114-5. PMID: 26275819Free PMC Article
Skolarikos A, Laguna MP, de la Rosette JJ
BJU Int 2012 Jul;110(2):170-8. Epub 2012 Mar 13 doi: 10.1111/j.1464-410X.2011.10847.x. PMID: 22414207

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...