Phenotypes of Craniofrontonasal Syndrome in Patients with a Pathogenic Mutation in EFNB1

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2013 Nov 28

PMID 24281372

Citations 18

Authors

M E P van den Elzen

S R F Twigg

J A C Goos

A J M Hoogeboom

A M W van den Ouweland

A O M Wilkie

I M J Mathijssen

Affiliations

Soon will be listed here.

Abstract

Craniofrontonasal syndrome (CFNS) is an X-linked developmental malformation, caused by mutations in the EFNB1 gene, which have only been described since 2004. A genotype-phenotype correlation seems not to be present. As it is of major importance to adequately counsel patients with EFNB1 mutations and their parents, and to improve diagnosis of new patients, more information about the phenotypic features is needed. This study included 23 patients (2 male, 21 female) with confirmed EFNB1 mutations. All patients underwent a thorough physical examination and photographs were taken. If available, radiological images were also consulted. Hypertelorism, longitudinal ridging and/or splitting of nails, a (mild) webbed neck and a clinodactyly of one or more toes were the only consistent features observed in all patients. Frequently observed phenotypic features were bifid tip of the nose (91%), columellar indentation (91%) and low implantation of breasts (90%). In comparison with anthropometric data of facial proportions, patients with CFNS had a significantly different face in multiple respects. An overview of all phenotypic features is shown. Patients with EFNB1 mutations have a clear phenotype. This study will facilitate genetic counseling of parents and patients, and contribute to the diagnostic and screening process of patients with suspected CFNS.

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References

Davy A, Bush J, Soriano P . Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome. PLoS Biol. 2006; 4(10):e315. PMC: 1563491. DOI: 10.1371/journal.pbio.0040315. View

Wieland I, Jakubiczka S, Muschke P, Cohen M, Thiele H, Gerlach K . Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet. 2004; 74(6):1209-15. PMC: 1182084. DOI: 10.1086/421532. View

Klein R . Eph/ephrin signaling in morphogenesis, neural development and plasticity. Curr Opin Cell Biol. 2004; 16(5):580-9. DOI: 10.1016/j.ceb.2004.07.002. View

Compagni A, Logan M, Klein R, Adams R . Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell. 2003; 5(2):217-30. DOI: 10.1016/s1534-5807(03)00198-9. View

Wieacker P, Wieland I . Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic paradox. Mol Genet Metab. 2005; 86(1-2):110-6. DOI: 10.1016/j.ymgme.2005.07.017. View

Twigg S, Babbs C, van den Elzen M, Goriely A, Taylor S, McGowan S . Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes. Hum Mol Genet. 2013; 22(8):1654-62. PMC: 3605834. DOI: 10.1093/hmg/ddt015. View

Wieland I, Jakubiczka S, Muschke P, Wolf A, Gerlach L, Krawczak M . Mapping of a further locus for X-linked craniofrontonasal syndrome. Cytogenet Genome Res. 2003; 99(1-4):285-8. DOI: 10.1159/000071605. View

Orr D, Slaney S, Ashworth G, Poole M . Craniofrontonasal dysplasia. Br J Plast Surg. 1997; 50(3):153-61. DOI: 10.1016/s0007-1226(97)91362-x. View

Natarajan U, Baraitser M, Nicolaides K, Gosden C . Craniofrontonasal dysplasia in two male sibs. Clin Dysmorphol. 1993; 2(4):360-4. View

10.

Kawamoto H, Heller J, Heller M, Urrego A, Gabbay J, Wasson K . Craniofrontonasal dysplasia: a surgical treatment algorithm. Plast Reconstr Surg. 2007; 120(7):1943-1956. DOI: 10.1097/01.prs.0000287286.12944.9f. View

11.

Young I . Craniofrontonasal dysplasia. J Med Genet. 1987; 24(4):193-6. PMC: 1049993. DOI: 10.1136/jmg.24.4.193. View

12.

Wallis D, Lacbawan F, Jain M, Der Kaloustian V, Steiner C, Moeschler J . Additional EFNB1 mutations in craniofrontonasal syndrome. Am J Med Genet A. 2008; 146A(15):2008-12. PMC: 2774847. DOI: 10.1002/ajmg.a.32388. View

13.

Hurst J, Baraitser M . Craniofrontonasal dysplasia. J Med Genet. 1988; 25(2):133-4. PMC: 1015457. DOI: 10.1136/jmg.25.2.133. View

14.

Cohen Jr M . Craniofrontonasal dysplasia. Birth Defects Orig Artic Ser. 1979; 15(5B):85-9. View

15.

Wieland I, Reardon W, Jakubiczka S, Franco B, Kress W, Vincent-Delorme C . Twenty-six novel EFNB1 mutations in familial and sporadic craniofrontonasal syndrome (CFNS). Hum Mutat. 2005; 26(2):113-8. DOI: 10.1002/humu.20193. View

16.

Kere J, Ritvanen A, MARTTINEN E, Kaitila I . Craniofrontonasal dysostosis: variable expression in a three-generation family. Clin Genet. 1990; 38(6):441-6. DOI: 10.1111/j.1399-0004.1990.tb03610.x. View

17.

Kwee M, Lindhout D . Frontonasal dysplasia, coronal craniosynostosis, pre- and postaxial polydactyly and split nails: a new autosomal dominant mutant with reduced penetrance and variable expression?. Clin Genet. 1983; 24(3):200-5. DOI: 10.1111/j.1399-0004.1983.tb02240.x. View

18.

Twigg S, Kan R, Babbs C, Bochukova E, Robertson S, Wall S . Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc Natl Acad Sci U S A. 2004; 101(23):8652-7. PMC: 423250. DOI: 10.1073/pnas.0402819101. View

19.

Apostolopoulou D, Stratoudakis A, Hatzaki A, Kaxira O, Panagopoulos K, Kollia P . A novel de novo mutation within EFNB1 gene in a young girl with craniofrontonasal syndrome. Cleft Palate Craniofac J. 2011; 49(1):109-13. DOI: 10.1597/10-247. View

20.

Shotelersuk V, Siriwan P, Ausavarat S . A novel mutation in EFNB1, probably with a dominant negative effect, underlying craniofrontonasal syndrome. Cleft Palate Craniofac J. 2006; 43(2):152-4. DOI: 10.1597/05-014.1. View