MedGen

Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation. [from GeneReviews]

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the KARS gene. [from MONDO]

Developmental and epileptic encephalopathy-89 (DEE89) is a severe autosomal recessive disorder characterized by profound global developmental delay with impaired intellectual development, absent speech, inability to sit or walk due to axial hypotonia and spastic quadriparesis, and onset of seizures in the first days or months of life. EEG shows suppression-burst pattern or hypsarrhythmia, consistent with DEE or a clinical diagnosis of West syndrome. More variable features include joint contractures with foot deformities, dysmorphic facial features with cleft palate, and omphalocele. Affected individuals have poor motor skills, poor eye contact, and lack of language development; some die in infancy or early childhood. Brain imaging may be normal or show nonspecific abnormalities (summary by Chatron et al., 2020). [from OMIM]

Retinitis pigmentosa-89 (RP89) is characterized by classic features of RP as well as features of ciliopathy, including postaxial polydactyly and renal and hepatic disease. Onset of symptoms is within the first decade of life (Cogne et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of RP, see 268000. [from OMIM]

Immunodeficiency-89 and autoimmunity (IMD89) is an autosomal recessive immune disorder characterized by adult onset of recurrent infections, allergies, microcytic anemia, and Crohn disease (see 266600) (Yang et al., 2020). [from OMIM]

Spermatogenic failure-89 (SPGF89) is characterized by male infertility due to severely reduced progressive motility of sperm (Sha et al., 2023). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

Autosomal dominant deafness-89 (DFNA89) is characterized by nonsyndromic progressive age-related hearing loss, with onset at birth or in early childhood (Brownstein et al., 2020). [from OMIM]

Autosomal recessive spastic paraplegia-89 (SPG89) is characterized by symptom onset in the first years of life. Affected individuals show delayed motor development with abnormal spastic gait and hyperreflexia of the lower limbs. Some patients may have mildly impaired intellectual development or learning difficulties (Deng et al., 2023). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800). [from OMIM]