NIH Rare Diseases

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 7Disease definitionCranio-cerebello-cardiac (3C) syndrome is a rare multiple congenital anomalies syndrome characterized by craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies (see these terms).EpidemiologyTo date Clinical description3C syndrome is a congenital disorder characterized by distinctive craniofacial features including, in decreasing frequency, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge, prominent occiput, prominent forehead, cleft palate, micrognathia, ocular coloboma. Additional craniofacial features encompass nevus flammeus (on forehead), low posterior hairline, sparse scalp hair, eyebrows and eyelashes, open mouth with protruding tongue, and short neck. In 80% of cases, cerebellar anomalies are present and include primarily Dandy-Walker malformation or Dandy-Walker variant, cerebellar vermis hypoplasia and enlargement of cisterna magma. Affected individuals have gross motor and speech delay and intellectual disability. The cardiovascular anomalies include atrial and ventricular septal defects, patent arterial duct, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart syndrome (see these terms), aortic or pulmonary stenosis, and other valvular anomalies. Postnatal short stature is noted in most patients, and growth hormone deficiency has been reported in two patients. Additional anomalies, noted in >10% of patients, include feeding difficulties, single umbilical artery, small hands with single transverse crease, camptodactyly, equinovarus deformity, hydronephrosis, shallow scrotum, undescended testis, cryptorchidism, micropenis, hypospadias, nail hypoplasia, hearing loss, malrotation of the gut. Skeletal defects may be present with rib and vertebral anomalies (hemivertebrae). Rarely observed features include ocular (congenital glaucoma, optic nerve atrophy with eyelid ptosis, heteochromatic iris, posterior embryotoxon), renal (multicystic dysplastic kidney, horseshoe kidneys, unilateral renal agenesis) and anal (anal atresia, anteriorly placed anus malformations) anomalies. Single occurrences of renal hypoplasia, nipple hypoplasia, penile hypoplasia, unilateral adrenal aplasia, immunodeficiency have also been reported.EtiologyThe exact etiology is still unknown but mutations in KIAA0196 (8q24.13; coding for strumpellin) have been identified in a First Nations cohort and these mutations may be involved in the pathophysiology of 3C syndrome.Diagnostic methodsThe diagnostic criteria for 3C syndrome include congenital heart malformation(s) other than isolated patent arterial duct; Dandy-Walker malformation, cerebellar vermis hypoplasia, or enlarged cisterna; and cleft palate, ocular coloboma or four of the following: prominent occiput, prominent forehead, hypertelorism, micrognathia, downslanting palpebral fissures, depressed nasal bridge, low-set ears.Differential diagnosisDifferential diagnosis includes Joubert syndrome, Ellis Van Creveld syndrome, Cornelia de Lange syndrome, distal monosomy 6p (see these terms) and Dandy Walker malformation.Antenatal diagnosisPrenatal diagnosis may be suspected after an ultrasound examination revealing characteristic major structural anomalies of 3C syndrome. Prenatal testing is available for families in which the disease-causing mutations have been previously identified.Genetic counselingSporadic and familial cases have been reported. Transmission is autosomal recessive. Phenotypic variability exists between siblings.Management and treatmentManagement is mainly symptomatic and multidisciplinary approaches including educational programs, physical, occupational, and speech therapy may help to improve hypotonia and reduce motor developmental delay. Cardiac malformation requires specific care, often surgery.PrognosisPrognosis is determined by the cardiovascular malformation. Motor delay is common and associated with hypotonia secondary to cerebellar anomalies.Visit the Orphanet disease page for more resources. Last updated: 9/17/2015

MalaCards based summary

Ritscher-Schinzel Syndrome 1, also known as 3c syndrome, is related to ritscher-schinzel syndrome and ritscher-schinzel syndrome 2, and has symptoms including macrocephaly, hypertelorism and low-set ears. An important gene associated with Ritscher-Schinzel Syndrome 1 is WASHC5 (WASH Complex Subunit 5). Affiliated tissues include heart, brain and kidney.

OMIM

The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay (summary by Leonardi et al., 2001; Seidahmed et al., 2011). (220210)

UniProtKB/Swiss-Prot

Ritscher-Schinzel syndrome 1: A developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay.

Disease Ontology

A Ritscher-Schinzel syndrome that has material basis in homozygous mutation in the KIAA0196 gene on chromosome 8q24.