MedGen

Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than 100. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk for GI cancers ranges from 11% to 86%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have also been reported. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) is present in most individuals with an SMAD4 pathogenic variant. [from GeneReviews]

TBC1D24-related disorders comprise a continuum of features that were originally described as distinct, recognized phenotypes: DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). Profound sensorineural hearing loss, onychodystrophy, osteodystrophy, intellectual disability / developmental delay, and seizures. Familial infantile myoclonic epilepsy (FIME). Early-onset myoclonic seizures, focal epilepsy, dysarthria, and mild-to-moderate intellectual disability. Progressive myoclonus epilepsy (PME). Action myoclonus, tonic-clonic seizures, progressive neurologic decline, and ataxia. Early-infantile epileptic encephalopathy 16 (EIEE16). Epileptiform EEG abnormalities which themselves are believed to contribute to progressive disturbance in cerebral function. Autosomal recessive nonsyndromic hearing loss, DFNB86. Profound prelingual deafness. Autosomal dominant nonsyndromic hearing loss, DFNA65. Slowly progressive deafness with onset in the third decade, initially affecting the high frequencies. [from GeneReviews]

Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than 100. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk for GI cancers ranges from 11% to 86%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have also been reported. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) is present in most individuals with an SMAD4 pathogenic variant. [from GeneReviews]

Spermatogenic failure-86 (SPGF86) is characterized by male infertility due to acrosomal defects of the spermatozoa, resulting in oocyte activation deficiency and fertilization failure. Some oocytes exhibit early embryonic arrest after successful fertilization with patient sperm using assisted reproductive technology (Xin et al., 2020; Wang et al., 2021). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

Immunodeficiency-86 (IMD86) is an autosomal recessive immunologic disorder characterized by susceptibility to mycobacterial disease after exposure to BCG vaccine. Affected individuals usually develop localized mycobacterial lymphadenopathy that can be successfully treated without subsequent episodes (summary by Kong et al., 2018). [from OMIM]

Autosomal recessive spastic paraplegia-86 (SPG86) is a complex neurologic disorder characterized by global developmental delay apparent from early childhood combined with early-onset progressive spasticity mainly affecting the lower limbs, but also affecting the upper limbs. Affected individuals have hyperreflexia, extensor plantar responses, pyramidal signs, and difficulty walking or inability to walk. Some may have joint contractures and foot or ankle deformities. Patients with SPG86 have impaired intellectual development with poor or absent speech, often with behavioral abnormalities. Brain imaging shows thin corpus callosum and white matter abnormalities. Rare patients may have seizures. The disorder is thus a complicated form of SPG (summary by Yahia et al., 2021, Miyake et al., 2022). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). [from OMIM]

Retinitis pigmentosa-86 (RP86) is characterized by night blindness followed by progressive narrowing of visual fields and decline in visual acuity, with typical findings of RP on fundus examination, including attenuated retinal vessels, waxy pallor of the optic disc, and bone spicule-like pigmentation (de Bruijn et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. [from OMIM]

Developmental and epileptic encephalopathy-86 (DEE86) is an X-linked neurologic syndrome characterized by severe and persistent seizures associated with EEG abnormalities beginning in the first few months of life, global developmental delay, severe motor deficits, dystonic movements, and dysmorphic facial features (Lentini et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Autosomal dominant deafness-86 (DFNA86) is characterized by late-onset progressive hearing loss through p53 (TP53; 191170)-mediated hair cell apoptosis (Zhang et al., 2020). [from OMIM]

Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (SKIC2; 600478) on chromosome 6p21. Reviews Bourgeois et al. (2018) analyzed a cohort of 96 patients with THES from 85 different families, drawing from published reports (37 patients) and their own recruitment (59 patients). Approximately two-thirds of the patients carried biallelic TTC37 mutations, and one-third had SKIVL2 mutations; in 8 (8.3%) of the patients, only 1 mutation could be identified. Intractable diarrhea was present in 100% of patients regardless of genotype, with hair abnormalities (woolly, brittle, easily removable) present in 90%. Facial dysmorphisms were observed in 84% of clinically described patients, comprising primarily large forehead, broad nasal root, and hypertelorism. Intrauterine growth retardation was frequent, seen in 70% of TTC37-mutated patients and 86% of SKIV2L-mutated patients; however, there was no significant difference in postnatal growth between the 2 groups. Liver disease was common, and more frequent in patients with mutation in SKIV2L (88%) than in TTC37 (51%); findings ranged from elevated liver enzymes and hepatomegaly to fibrosis and cirrhosis. Immunodeficiency was reported in about half of clinically explored patients, presenting as low immunoglobulin count or lack of antibody response to immunization. In addition, approximately 40% to 50% of patients exhibited dermatologic abnormalities, mostly cafe-au-lait spots located on the lower limbs. Overall, the authors noted that THES patients with mutation in either gene exhibit remarkably similar clinical signs, involving primarily the gastrointestinal tract, hair, and face, and are indistinguishable in clinical practice. However, a few differences emerged from analysis of the cohort, with SKIV2L-associated THES showing an earlier onset and/or greater severity, with more severe liver disease and significantly smaller height and weight at birth. [from OMIM]

Keratoconus is a noninflammatory disorder in which there is thinning and ectasia of the cornea. The estimated prevalence varies from 29 to 86 per 100,000, although the condition may be underreported. The onset of disease is typically after puberty, with subsequent progression at a variable rate over the following decades. Visual acuity is initially reduced by irregular corneal astigmatism but scarring can also develop (summary by Liskova et al., 2010). For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300). [from OMIM]