Limb disorders

Gene: EFNB1

I don't know

Gene suggested for the panel

Created: 1 Aug 2019, 5:10 p.m. | Last Modified: 1 Aug 2019, 5:10 p.m.

Panel Version: 1.24

I don't know

Comment on list classification: Clear gene:disease association but relatively minor / non-specific digital features. Rating amber based on advice from Genomics England clinical team.

Created: 25 Nov 2019, 10:33 p.m. | Last Modified: 25 Nov 2019, 10:33 p.m.

Panel Version: 1.111

Associated with Craniofrontonasal dysplasia (304110) in OMIM and CRANIOFRONTONASAL SYNDROME in Gene2Phenotype (confirmed). In OMIM Asymmetric lower limb shortness, Joint laxity, Syndactyly, Brachydactyly, Fifth finger clinodactyly and Broad halluces are listed as limb features of the condition and a similar list is given in Gene2Phenotype.

CFNS shows a very unusual pattern of X-linked inheritance, in which most affected patients are females and obligate male carriers show no or only mild manifestation, such as hypertelorism .

PMID: 15166289 - Twigg et al 2014 - identified significant mutations in EFNB1 in all 20 unrelated Craniofrontonasal syndrome females studied, including nine different de novo mutations. Of the 20, 2 had duplex thumb/hallux and 1 showed lower-limb asymmetry in addition to other features such as coronal craniosynostosis and cleft lip and/or palate.

PMID: 23335590 - Twigg et al 2013 - Six severely affected sporadic males with a diagnosis of CFNS. They identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5′ untranslated region (UTR). 4/6 patients had brachydactyly and/or syndactyly. Clinodactyly was also seen in 3 patients.

PMID: 15124102 - Weiland et al 2004 - 3 families with variants (deletion of exons 2–5 and two missense variants) in EFNB1 and CFNS. In Family 2 brachydactyly was an observed phenotype. In Family 3 one female showed complete syndactyly of the third and fourth finger on the left side.

Created: 31 Jul 2019, 3:49 p.m. | Last Modified: 31 Jul 2019, 3:49 p.m.

Panel Version: 1.9

Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list

Created: 31 Jul 2019, 3:12 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Craniofrontonasal syndrome, 304110

Publications

• 15166289
• 23335590
• 15124102

Mode of pathogenicity
Other