Novel FREM1 mutations in a patient with MOTA syndrome: Clinical findings, mutation update and review of FREM1-related disorders literature

Abstract

Manitoba-oculo-tricho-anal (MOTA) syndrome is an uncommon condition arising from biallelic mutations of FREM1 gene and clinically characterized by a variable spectrum of eyelid malformations, aberrant hairline, bifid or broad nasal tip, and gastrointestinal anomalies. In this report, we describe a patient with a phenotype compatible with MOTA syndrome (aberrant anterior hair line, hypertelorism, unilateral anophthalmia, and bifid and broad nasal tip) in whom two novel FREM1 mutations (c.305 A > G, p.Asp102Gly; and c.2626delG, p.Val876Tyrfs*16) were identified in the compound heterozygous state, thus broadening the mutational spectrum of the disease. We performed a literature review of the clinical and genetic features of individuals carrying FREM1 mutations.

Keywords: Aberrant hairline; Anal malformations; Anophthalmia; Bifid nasal tip; Coloboma; Cryptophthalmos; Eyelid malformations; FREM1; Hypertelorism; MOTA syndrome; Manitoba-oculo-tricho-anal syndrome.