MedGen

Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported. [from GeneReviews]

Immunodeficiency-36 with lymphoproliferation (IMD36) is an autosomal dominant primary immunodeficiency with a highly heterogeneous clinical phenotype, characterized primarily by recurrent respiratory tract infections, lymphoproliferation, and antibody deficiency. Other features include growth retardation, mild neurodevelopmental delay, and autoimmunity. The major complication is development of B-cell lymphoma (Elkaim et al., 2016). [from OMIM]

Spinocerebellar ataxia type 15 (SCA15) is characterized by slowly progressive gait and limb ataxia, often in combination with ataxic dysarthria, titubation, upper limb postural tremor, mild hyperreflexia, gaze-evoked nystagmus, and impaired vestibuloocular reflex gain. Onset is between ages seven and 72 years, usually with gait ataxia but sometimes with tremor. Affected individuals remain ambulatory for ten to 54 years after symptom onset. Mild dysphagia usually after two or more decades of symptoms has been observed in members of multiple affected families and movement-induced oscillopsia has been described in one member of an affected family. [from GeneReviews]

Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment. [from GeneReviews]

The 10q22.3-q23.2 region is characterized by a complex set of low-copy repeats (LCRs), which can give rise to various genomic changes mediated by nonallelic homologous recombination (NAHR). Recurrent deletions of chromosome 10q22.3-q23.2, including the BMPR1A gene (601299) have been associated with dysmorphic facies, developmental delay, and multiple congenital anomalies. Some patients with deletions that extend distally to include the PTEN gene (601728) have a more severe phenotype with infantile/juvenile polyposis, macrocephaly, dysmorphic facial features, and developmental delay (summary by van Bon et al., 2011). [from OMIM]

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100). [from OMIM]

Hyper-IgE syndrome-4B with recurrent infections (HIES4B) is an autosomal recessive immunologic disorder characterized by early childhood onset of recurrent infections and skeletal abnormalities, including craniosynostosis and scoliosis. Patients are mainly susceptible to bacterial infections that affect the respiratory tract, skin, and eye. Immunologic workup shows increased serum IgE, intermittent eosinophilia, and impaired IL6 (147620) and IL27 (608273) downstream signaling that affects the development and function of certain B- and T-cell populations, as well as the acute-phase response; IL11 (147681) signaling in fibroblasts is also affected (summary by Shahin et al., 2019). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060). [from OMIM]

Congenital hydrocephalus-4 (HYC4) is characterized by inadequate passage of cerebrospinal fluid (CSF) from its point of production to its point of absorption, in the absence of obstruction (communicating hydrocephalus). Patients undergo surgical shunting at birth because of extreme ventriculomegaly. Patients have neurodevelopmental delay and epilepsy (Furey et al., 2018). [from OMIM]

Tan-Almurshedi syndrome (TANALS) is an autosomal recessive neurodevelopmental disorder characterized by intrauterine growth retardation, poor overall growth with short stature and microcephaly, hypotonia, global developmental delay with impaired intellectual development, poor or absent speech, spasticity, and dysmorphic facial features (Westrip et al., 2023). [from OMIM]

Severe congenital liver disease (SCOLIV) is an autosomal recessive disorder characterized by the onset of progressive hepatic dysfunction usually in the first years of life. Affected individuals show feeding difficulties with failure to thrive and features such as jaundice, hepatomegaly, and abdominal distension. Laboratory workup is consistent with hepatic insufficiency and may also show coagulation defects, anemia, or metabolic disturbances. Cirrhosis and hypernodularity are commonly observed on liver biopsy. Many patients die of liver failure in early childhood (Moreno Traspas et al., 2022). [from OMIM]

Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. [from HPO]