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Renal cysts and diabetes syndrome(RCAD)

MedGen UID:
96569
Concept ID:
C0431693
Disease or Syndrome
Synonyms: Familial hypoplastic, glomerulocystic kidney; FJHN atypical; Glomerulocystic kidney disease, hypoplastic type; Hyperuricemic nephropathy, familial juvenile, atypical; Maturity-onset diabetes of the young, type 5; MODY type 5; RCAD
SNOMED CT: Maturity-onset diabetes of the young, type 5 (609572000); MODY5 - maturity-onset diabetes of the young type 5 (609572000); Renal cysts and diabetes syndrome (609572000); Familial hypoplastic, glomerulocystic kidney (253864004); HNF1B-MODY - HNF1 homeobox B maturity-onset diabetes of the young type 5 (609572000); HNF1B (HNF1 homeobox B) monogenic diabetes mellitus (609572000); HNF1B monogenic diabetes mellitus (609572000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): HNF1B (17q12)
 
Monarch Initiative: MONDO:0007669
OMIM®: 137920
Orphanet: ORPHA93111

Definition

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). [from GeneReviews]

Additional description

From OMIM
Renal cysts and diabetes syndrome (RCAD) is an autosomal dominant multisystemic disorder with significant phenotypic heterogeneity. It is characterized by (1) nondiabetic renal disease resulting from abnormal renal development, and (2) diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelvises, abnormal calyces, small kidney, single kidney, and horseshoe kidney. Some patients with renal disease have hyperuricemic nephropathy with tubulointerstitial changes on biopsy, consistent with autosomal dominant tubulointerstitial kidney disease (ADTKD). Affected individuals may also have abnormalities of the genital tract, including vaginal aplasia, rudimentary uterus, bicornuate uterus, epididymal cysts, and atresia of the vas deferens (Bingham et al., 2001; Fajans et al., 2001; Bellanne-Chantelot et al., 2004; Edghill et al., 2006; summary by Devuyst et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of MODY, see 606391. For a discussion of genetic heterogeneity of ADTKD and a discussion of the revised nomenclature of these disorders, see ADTKD1 (162000). The renal abnormalities are part of a spectrum of malformations known as congenital anomalies of the kidney and urinary tract (CAKUT; see 610805) (summary by Nakayama et al., 2010).  http://www.omim.org/entry/137920

Clinical features

From HPO
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
An increased concentration of glucose in the urine.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Abnormality of the kidney
MedGen UID:
78593
Concept ID:
C0266292
Congenital Abnormality
An abnormality of the kidney.
Unilateral renal agenesis
MedGen UID:
75607
Concept ID:
C0266294
Congenital Abnormality
A unilateral form of agenesis of the kidney.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
Uterine hypoplasia
MedGen UID:
120575
Concept ID:
C0266399
Congenital Abnormality
Underdevelopment of the uterus.
Atretic vas deferens
MedGen UID:
75613
Concept ID:
C0266445
Congenital Abnormality
Abnormal closure or blockage of the vas deferens.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Ureteropelvic junction obstruction
MedGen UID:
105482
Concept ID:
C0521619
Anatomical Abnormality
Blockage of urine flow from the renal pelvis to the proximal ureter.
Abnormality of the genital system
MedGen UID:
155422
Concept ID:
C0744356
Finding
An abnormality of the genital system.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Decreased numbers of nephrons
MedGen UID:
436031
Concept ID:
C2673888
Finding
A reduction in the count of nephrons per kidney.
Renal cyst
MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
A fluid filled sac in the kidney.
Multiple glomerular cysts
MedGen UID:
893156
Concept ID:
C4022013
Pathologic Function
The presence of many cysts in the glomerulus of the kidney related to dilatation of the Bowman's capsule.
Reduced sperm motility
MedGen UID:
907698
Concept ID:
C4082176
Finding
An abnormal reduction in the mobility of ejaculated sperm.
Abnormal renal morphology
MedGen UID:
1633142
Concept ID:
C4551596
Anatomical Abnormality
Any structural anomaly of the kidney.
Epididymal cyst
MedGen UID:
1778106
Concept ID:
C5442141
Anatomical Abnormality
A smooth, extratesticular, spherical cyst in the head of the epididymis.
Pancreatic hypoplasia
MedGen UID:
539808
Concept ID:
C0266267
Congenital Abnormality
Hypoplasia of the pancreas.
Exocrine pancreatic insufficiency
MedGen UID:
75647
Concept ID:
C0267963
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Biliary tract abnormality
MedGen UID:
108201
Concept ID:
C0549613
Finding
An abnormality of the biliary tree.
Pancreatic atrophy
MedGen UID:
1052705
Concept ID:
CN376669
Finding
Wasting (shrinking) of the pancreas.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Gout
MedGen UID:
42280
Concept ID:
C0018099
Disease or Syndrome
Recurrent attacks of acute inflammatory arthritis of a joint or set of joints caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Impaired glucose tolerance
MedGen UID:
852424
Concept ID:
C0151671
Finding
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Maturity onset diabetes mellitus in young
MedGen UID:
87433
Concept ID:
C0342276
Disease or Syndrome
Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17q12. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q31. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Abnormality of alkaline phosphatase level
MedGen UID:
892397
Concept ID:
C4025328
Finding
An abnormality of alkaline phosphatase level.

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