Familial Hirschsprung Disease

Gene: L1CAM

Green List (high evidence)

Comment when marking as ready: Marked L1CAM as ready: August 3rd 2017.

Created: 3 Aug 2017, 9:36 a.m.

Comment on list classification: Updated rating from Amber to Green based on Green expert review and sufficient (>3) cases of L1CAM variants in patients with concurrent X-linked hydrocephalus and Hirschsprung disease.

Created: 3 Aug 2017, 9:35 a.m.

Comment on list classification: Updated rating from Red to Amber awaiting external review. >3 cases of L1CAM variants in patients with concurrent X-linked hydrocephalus and Hirschsprung disease.

Created: 1 Aug 2017, 2:21 p.m.

Added a 'monogenic-polygenic' tag based on patient in PMID:22344793 who carried both L1CAM and RET variants.

Created: 1 Aug 2017, 2:20 p.m.

In 2 brothers with hydrocephalus (MIM:307000) and Hirschsprung disease, Okamoto et al. (2004, PMID:15148591) identified a splice-site mutation in L1CAM.A third case had a nonsense variant in exon 22 (C2974T, Cln992Stop) and hydrocephalus alongside HSCR.

Created: 1 Aug 2017, 2:19 p.m.

Jackson et al., 2009 (PMID:19641926) describe a case of a patient with concurrent X-linked hydrocephalus and Hirschsprung disease. The patient was hemizygous for a R558X hemizygous variation in the L1CAM gene.

Created: 1 Aug 2017, 2:19 p.m.

Fernández et al., 2012 (PMID:22344793) describe a new patient with concurrent X-linked hydrocephalus and Hirschsprung disease together with a G698R hemizygous mutation in L1CAM. The patient also carried the RET mutation c.73 + 9277T > C.

Created: 1 Aug 2017, 2:19 p.m.

Parisi et al. (2002, PMID:11857550) describe a male infant who had severe hydrocephalus (MIM:307000) and Hirschsrpung disease. The patient had a 2254G-A mutation in L1CAM (V752M). Parisi et al. stated that this patient represented the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation.

Created: 1 Aug 2017, 2:19 p.m.

In a child with features of X-linked hydrocephalus (307000) who also had Hirschsprung disease and cleft palate, Okamoto et al. (1997, PMID:9279760) identified a 2-bp deletion of exon 18 in the L1CAM gene, resulting in a frameshift and premature termination. XLH and HSCR may be independent events in this patient, but the authors suggested that L1CAM may contribute to both phenotypes.

Created: 1 Aug 2017, 2:18 p.m.