MedGen

Perlman syndrome (PRLMNS) is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012). [from OMIM]

Cat eye syndrome (CES) is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11). [from OMIM]

MEDNIK syndrome is a severe multisystem disorder characterized by impaired intellectual development, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (summary by Montpetit et al., 2008). Patients with MEDNIK exhibit distinct dysmorphic features, including high forehead, upslanting palpebral fissures, depressed nasal bridge, and low-set ears, as well as growth retardation and moderate to severe intellectual disability, with brain atrophy on imaging. Other features include sensorineural deafness, enteropathy with congenital diarrhea, abnormalities of copper metabolism associated with liver disease, and ichthyosis, hyperkeratosis, and erythroderma. Peripheral neuropathy has also been observed in adult patients (Martinelli et al., 2013). MEDNIK syndrome shows phenotypic similarities to CEDNIK syndrome (609528). [from OMIM]

PACS1 neurodevelopmental disorder (PACS1-NDD) is characterized by mild-to-severe neurodevelopmental delays. Language skills are more severely affected than motor skills. Hypotonia is reported in about a third of individuals and is noted to improve over time. Approximately 60% of individuals are ambulatory. Feeding difficulty is common, with 25% requiring gastrostomy tube to maintain appropriate caloric intake. Other common features include constipation, seizures, behavioral issues, congenital heart anomalies, short stature, and microcephaly. Common facial features include hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set and simple ears, smooth philtrum, wide mouth with downturned corners, thin upper vermilion, and wide-spaced teeth. To date approximately 35 individuals with PACS1-NDD have been reported. [from GeneReviews]

Seizures, scoliosis, and macrocephaly/microcephaly syndrome (SSMS) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay apparent from early infancy, impaired intellectual development, behavioral problems, poor or absent speech, seizures, dysmorphic facial features with macro- or microcephaly, and skeletal abnormalities, including scoliosis and delayed bone age. Other features may include hypotonia, gastrointestinal problems, and exostoses (summary by Gentile et al., 2019). [from OMIM]

A rare vascular malformation disorder with cutaneous and visceral lesions frequently associated with serious, potentially fatal bleeding and anemia. [from ORDO]

An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis. [from HPO]

Visceral myopathy-2 (VSCM2) is characterized by gastrointestinal symptoms resulting from intestinal dysmotility and paresis, including abdominal distention, pain, nausea, and vomiting. Some patients exhibit predominantly esophageal symptoms, with hiatal hernia and severe reflux resulting in esophagitis and stricture, whereas others experience chronic intestinal pseudoobstruction. Bladder involvement resulting in megacystis and megaureter has also been observed and may be evident at birth (Dong et al., 2019; Gilbert et al. (2020)). [from OMIM]

Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA) is an autosomal recessive disorder characterized by severe global developmental delay with poor motor and intellectual function apparent soon after birth, as well as postnatal progressive microcephaly. Most patients develop early-onset, frequent, and often intractable seizures, compatible with an epileptic encephalopathy. Other features include poor feeding, poor overall growth, absent speech, poor or absent eye contact, inability to achieve walking, hypotonia, and peripheral spasticity. Brain imaging usually shows progressive cerebral atrophy, thin corpus callosum, and abnormalities in myelination. Death in childhood may occur (summary by Siekierska et al., 2019). [from OMIM]

Autosomal recessive cutis laxa type ID (ARCL1D) is characterized by facial dysmorphism, joint hypermobility, muscle hypotonia, and multiple severe herniations, including inguinal, ventral, diaphragmatic, sciatic, and obturator, as well as large diverticula of the gastrointestinal tract and urinary bladder. The skin is thin and translucent with easy bruising; the degree of laxity is variable and progresses with age in some patients (Megarbane et al., 2012; Bizzari et al., 2020; Driver et al., 2020; Verlee et al., 2021). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). [from OMIM]

Pontocerebellar hypoplasia type 13 (PCH13) is an autosomal recessive disorder characterized by global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable (summary by Uwineza et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596). [from OMIM]

X-linked intellectual disorder-112 (XLID112) is a neurodevelopmental disorder characterized by developmental delay, with speech delay more prominent than motor delay, autism or autism traits, and variable dysmorphic features. Affected females have been reported, which appears to be related to skewed X-inactivation (summary by Hiatt et al., 2023). [from OMIM]

Abnormal twisting of a portion of intestine around itself or around a stalk of mesentery tissue. [from HPO]