Ritscher-Schinzel syndrome(RTSC1)

MedGen UID:: 163220
•Concept ID:: C0796137
•: Disease or Syndrome

Synonyms:	3C syndrome; Cranio-cerebello-cardiac dysplasia; Dandy-Walker like malformation with atrioventricular septal defect; Dandy-Walker-like malformation with ASD; Ritscher-Schinzel cranio-cerebello-cardiac syndrome; RTSC1
SNOMED CT:	Craniocerebellocardiac dysplasia (718556007); Ritscher Schinzel syndrome (718556007); 3C syndrome (718556007); Cranio-cerebello-cardiac dysplasia syndrome (718556007)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). X-linked recessive inheritance MedGen UID: 375779 •Concept ID: C1845977 • Finding Source: Orphanet A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. See: This record Autosomal recessive inheritance (Orphanet) X-linked recessive inheritance (Orphanet)

Monarch Initiative:	MONDO:0019078
OMIM®:	220210
OMIM® Phenotypic series:	PS220210
Orphanet:	ORPHA7

Definition

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 delayed psychomotor development (summary by Leonardi et al., 2001; Elliott et al., 2013). Genetic Heterogeneity of Ritscher-Schinzel Syndrome See also RTSC2 (300963), caused by mutation in the CCDC22 gene (300859) on chromosome Xp11; RTSC3 (619135), caused by mutation in the VPS35L gene (618981) on chromosome 16p12; and RTSC4 (619435), caused by mutation in the DPYSL5 gene (608383) on chromosome 2p23. [from OMIM]

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVRitscher-Schinzel syndrome

Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
- Ritscher-Schinzel syndrome

Follow this link to review classifications for Ritscher-Schinzel syndrome in Orphanet.

Recent clinical studies

Etiology

A novel mutation in KIAA0196: identification of a gene involved in Ritscher-Schinzel/3C syndrome in a First Nations cohort.

Elliott AM, Simard LR, Coghlan G, Chudley AE, Chodirker BN, Greenberg CR, Burch T, Ly V, Hatch GM, Zelinski T
J Med Genet 2013 Dec;50(12):819-22. Epub 2013 Sep 24 doi: 10.1136/jmedgenet-2013-101715. PMID: 24065355

The 3C syndrome: evolution of the phenotype and growth hormone deficiency.

Wheeler PG, Sadeghi-Nejad A, Elias ER
Am J Med Genet 1999 Nov 5;87(1):61-4. doi: 10.1002/(sici)1096-8628(19991105)87:1<61::aid-ajmg12>3.0.co;2-k. PMID: 10528249

See all (2)

Diagnosis

Expanding the pre- and postnatal phenotype of WASHC5 and CCDC22 -related Ritscher-Schinzel syndromes.

Neri S, Maia N, Fortuna AM, Damasio J, Coale E, Willis M, Jorge P, Højte AF, Fenger CD, Møller RS, Bayat A
Eur J Med Genet 2022 Nov;65(11):104624. Epub 2022 Sep 18 doi: 10.1016/j.ejmg.2022.104624. PMID: 36130690

Delineating the CCDC22-related Ritscher-Schinzel syndrome phenotype in the original family.

Rodgers J, Richmond CM, McGaughran J
Am J Med Genet A 2022 Nov;188(11):3324-3330. Epub 2022 Sep 8 doi: 10.1002/ajmg.a.62963. PMID: 36073196

Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?

Gjerulfsen CE, Møller RS, Fenger CD, Hammer TB, Bayat A
Eur J Med Genet 2021 Jul;64(7):104246. Epub 2021 May 18 doi: 10.1016/j.ejmg.2021.104246. PMID: 34020006

Ritscher-Schinzel cranio-cerebello-cardiac (3C) syndrome: report of four new cases and review.

Leonardi ML, Pai GS, Wilkes B, Lebel RR
Am J Med Genet 2001 Aug 15;102(3):237-42. PMID: 11484200

Ritscher-Schinzel (3C) syndrome: documentation of the phenotype.

Kosaki K, Curry CJ, Roeder E, Jones KL
Am J Med Genet 1997 Feb 11;68(4):421-7. doi: 10.1002/(sici)1096-8628(19970211)68:4<421::aid-ajmg10>3.0.co;2-u. PMID: 9021015

See all (10)

Therapy

The 3C syndrome: evolution of the phenotype and growth hormone deficiency.

Wheeler PG, Sadeghi-Nejad A, Elias ER
Am J Med Genet 1999 Nov 5;87(1):61-4. doi: 10.1002/(sici)1096-8628(19991105)87:1<61::aid-ajmg12>3.0.co;2-k. PMID: 10528249

See all (1)

Prognosis

Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.

Healy MD, McNally KE, Butkovič R, Chilton M, Kato K, Sacharz J, McConville C, Moody ERR, Shaw S, Planelles-Herrero VJ, Yadav SKN, Ross J, Borucu U, Palmer CS, Chen KE, Croll TI, Hall RJ, Caruana NJ, Ghai R, Nguyen THD, Heesom KJ, Saitoh S, Berger I, Schaffitzel C, Williams TA, Stroud DA, Derivery E, Collins BM, Cullen PJ
Cell 2023 May 11;186(10):2219-2237.e29. doi: 10.1016/j.cell.2023.04.003. PMID: 37172566 Free PMC Article

Ritscher-Schinzel cranio-cerebello-cardiac (3C) syndrome: report of four new cases and review.

Leonardi ML, Pai GS, Wilkes B, Lebel RR
Am J Med Genet 2001 Aug 15;102(3):237-42. PMID: 11484200

The 3C syndrome: evolution of the phenotype and growth hormone deficiency.

Wheeler PG, Sadeghi-Nejad A, Elias ER
Am J Med Genet 1999 Nov 5;87(1):61-4. doi: 10.1002/(sici)1096-8628(19991105)87:1<61::aid-ajmg12>3.0.co;2-k. PMID: 10528249

Sibs with Ritscher-Schinzel (3C) syndrome and anal malformations.

Orstavik KH, Bechensteen AG, Fugelseth D, Orderud W
Am J Med Genet 1998 Jan 23;75(3):300-3. PMID: 9475602

See all (4)