MedGen

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. [from GeneReviews]

McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly (PAP), congenital heart disease (CHD), and hydrometrocolpos (HMC) in females and genital malformations in males (most commonly hypospadias, cryptorchidism, and chordee). HMC in infants usually presents as a large cystic abdominal mass arising out of the pelvis, caused by dilatation of the vagina and uterus as a result of the accumulation of cervical secretions from maternal estrogen stimulation. HMC can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. PAP is the presence of additional digits on the ulnar side of the hand and the fibular side of the foot. A variety of congenital heart defects have been reported including atrioventricular canal, atrial septal defect, ventricular septal defect, or a complex congenital heart malformation. [from GeneReviews]

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]

Baller-Gerold syndrome (BGS) can be suspected at birth in an infant with craniosynostosis and upper limb abnormality. The coronal suture is most commonly affected; the metopic, lambdoid, and sagittal sutures may also be involved alone or in combination. Upper limb abnormality can include a combination of thumb hypo- or aplasia and radial hypo- or aplasia and may be asymmetric. Malformation or absence of carpal or metacarpal bones has also been described. Skin lesions may appear anytime within the first few years after birth, typically beginning with erythema of the face and extremities and evolving into poikiloderma. Slow growth is apparent in infancy with eventual height and length typically at 4 SD below the mean. [from GeneReviews]

Johanson-Blizzard syndrome is an autosomal recessive disorder characterized by poor growth, mental retardation, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency (summary by Al-Dosari et al., 2008). [from OMIM]

FREM1 autosomal recessive disorders include: Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR syndrome), and isolated congenital anomalies of kidney and urinary tract (CAKUT). MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and renal malformations (e.g., renal agenesis, renal dysplasia). Typically the eye manifestations of MOTA syndrome are absent. FREM1-CAKUT was identified in one individual with bilateral vesicoureteral reflux (VUR) and a second individual with VUR and renal hypodysplasia. [from GeneReviews]

The Currarino syndrome is an autosomal dominant form of hereditary sacral dysgenesis that classically consists of the triad of sacral malformation, presacral mass, and anorectal malformations. However, other features include neonatal-onset bowel obstruction, chronic constipation, recurrent perianal sepsis, renal/urinary tract anomalies, female internal genital anomalies, tethered spinal cord, and anterior meningocele. There is marked inter- and intrafamilial variability, and up to 33% of patients are asymptomatic (summary by Wang et al., 2006). [from OMIM]

IVIC syndrome (IVIC) is an autosomal dominant disorder characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral nonprogressive mixed hearing loss. More variable features include heart involvement, mild thrombocytopenia and leukocytosis (before age 50), shoulder girdle hypoplasia, imperforate anus, kidney malrotation, and rectovaginal fistula (summary by Paradisi and Arias, 2007). [from OMIM]

An EEC syndrome characterized by autosomal dominant inheritance that has material basis in variation in the chromosome region 7q11.2-q21.3. [from MONDO]

Any secretory diarrhea in which the cause of the disease is a mutation in the SPINT2 gene. [from MONDO]

CODAS is an acronym for cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is a rare disorder characterized by a distinctive constellation of features that includes developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts (summary by Strauss et al., 2015). [from OMIM]

Syndrome with the association of toe syndactyly, facial dysmorphism including telecanthus and a broad nasal tip, urogenital malformations and anal atresia. Around ten cases have been reported so far. The syndrome is caused by mutations in the FAM58A gene (located on the X chromosome) encoding a protein of unknown function. [from SNOMEDCT_US]

Any inflammatory bowel disease in which the cause of the disease is a mutation in the IL10RB gene. [from MONDO]

PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria. [from GeneReviews]

Carey et al. (1978) gave the name OEIS complex to a combination of defects comprising omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. This rare complex is thought to represent the most severe end of a spectrum of birth defects, the exstrophy-epispadias sequence, which, in order of increasing severity, includes phallic separation with epispadias, pubic diastasis, exstrophy of the bladder (600057), cloacal exstrophy, and OEIS complex. Very few instances of recurrence of anomalies in this cluster have been reported. [from OMIM]

CDAGS syndrome is characterized by craniosynostosis and clavicular hypoplasia, delayed closure of the fontanel, anal and genitourinary anomalies, and skin eruption of porokeratotic lesions (Mendoza-Londono et al., 2005). [from OMIM]

An abnormality of the anus or rectum. [from HPO]

White-Kernohan syndrome (WHIKERS) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have abnormalities of other systems, including genitourinary and skeletal (summary by White et al., 2021). [from OMIM]

The presence of a fistula between the vagina and the rectum. [from HPO]