FRAS1 gene

Overview
Microphthalmia, anophthalmia, coloboma (MAC)
Anterior segment dysgenesis
References

Overview

Gene (OMIM No.)	FRAS1 (#607830)
Function of gene/protein	Protein: fraser extracellular matrix complex subunit 1 Part of the FRAS/FREM complex, which is vital during embryogenesis The complex is located in cells basement membranes, and plays a role in anchoring cell layers in tissues
Clinical phenotype (OMIM phenotype no.)	Fraser syndrome 1 (#219000)
Inheritance	Autosomal recessive
Ocular features	Cryptophthalmos (a continuous layer of skin over the eyeball with absent eyelids and palpebral fissures) Microphthalmia, anophthalmia, coloboma (MAC) spectrum Absent/poor development of eyelashes, gland structures, conjunctival sac Anterior segment dysgenesis
Systemic features	Main features: Cutaneous syndactyly of both upper and lower limbs Laryngeal malformation (stenosis/atresia) Genital anomalies (micropenis, hypospadias, cryptorchidism, clitoral enlargement, vaginal atresia, bicornuate uterus) Additional features: Microcephaly, meningomyelocele, encephalocele Orofacial clefting (lip, palate, uvula) Nasal anomalies (hypoplastic, notched nares; broad, low nasal bridge; midline nasal cleavage) Middle and external ear malformations Unusual hairline with hair growth on temples extending to lateral eyebrow Displacement of the umbilicus and nipples Renal agenesis/hypoplasia Diastasis of pubic symphysis Intellectual disability
Key investigations	B-scan USS to measure axial length to document microphthalmia Electrophysiology MRI brain and orbit Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosis	Next generation sequencing Targeted gene panels (MAC) Whole genome sequencing
Management	Ocular Management of MAC Management of anterior segment dysgenesis Input from adnexal and corneal specialists usually required for cryptophthalmos Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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References

Gupta SP, Saxena RC. CRYPTOPHTHALMOS. Br J Ophthalmol. 1962;46(10):629‐632
Petrou P, Pavlakis E, Dalezios Y, Galanopoulos VK, Chalepakis G. Basement membrane distortions impair lung lobation and capillary organization in the mouse model for fraser syndrome. J Biol Chem. 2005;280(11):10350‐10356
van Haelst MM, Maiburg M, Baujat G, et al. Molecular study of 33 families with Fraser syndrome new data and mutation review. Am J Med Genet A. 2008;146A(17):2252‐2257
Vrontou S, Petrou P, Meyer BI, et al. Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice. Nat Genet. 2003;34(2):209‐214
Saleh GM, Hussain B, Verity DH, Collin JR. A surgical strategy for the correction of Fraser syndrome cryptophthalmos. Ophthalmology. 2009;116(9):1707‐1712
Slavotinek AM, Tifft CJ. Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet. 2002;39(9):623‐633. doi:10.1136/jmg.39.9.623

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Updated on November 30, 2020

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