A familial case of Muenke syndrome. Diverse expressivity of theFGFR3Pro252Arg mutation – case report and review of the literature

Abstract

Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s. Muenke syndrome is an autosomal dominant disorder characterized mainly by coronal suture craniosynostosis, hearing impairment and intellectual disability. The syndrome is defined molecularly by a unique point mutation c.749C > G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. Despite the fact that the mutation rate at this nucleotide is one of the most frequently described in human genome, few Muenke familial case reports are published in current literature. We describe individuals among three generations of a Greek family who are carriers of the same mutation. Medical record and physical examination of family members present a wide spectrum of clinical manifestations. In particular, a 38-year-old woman and her father appear milder clinical findings regarding craniofacial characteristics compared to her uncle and newborn female child. This familial case illustrates the variable expressivity of Muenke syndrome in association with an identical gene mutation.

Quantitative Craniofacial Analysis and Generation of Human Induced Pluripotent Stem Cells for Muenke Syndrome: A Case Report

“…Due to variable expressivity and incomplete penetrance, the presentation of MS ranges from a complete absence of clinical signs to severe and life-threatening consequences of defective skull growth, such as craniosynostosis, hearing loss, and increased intracranial pressure [6]. Furthermore, many MS traits have considerable overlap with other craniosynostosis syndromes.…”

“…Characterized by incomplete penetrance and variable expressivity [3], MS is a rare and complex disease that remains an immense challenge to study, diagnose, and treat. Several studies have documented the qualitative clinical phenotype of MS, which includes, but is not limited to, uni-or bilateral premature fusion of one or more cranial sutures (craniosynostosis), macrocephaly without craniosynostosis, dysmorphic craniofacial features, dental malocclusion, midfacial hypoplasia, and a high arch palate [4][5][6][7][8][9][10][11][12]. However, to date, very few quantitative craniofacial morphology studies have been reported.…”

Genome-wide association study in craniosynostosis condition using innovative systematic bioinformatic analysis tools and techniques: Future prospective and clinical practice

“…MS is an autosomal dominant disorder characterized by coronal suture CS. MS in the association with an identical gene mutation, an unique point mutation c.749C > G in exon 7 of the FGFR3 gene involved with MS.[ 15 ] Sagittal CS: Sagittal CS is the most common form of CS found in India. Children were the affected group, approximately one in every 5,000 newborn.…”

Craniosynostosis Syndromes: Genetics to Imaging

“…8). 71,72 Another mutation, A391E (p.Ala391Glu), is associated with the crouzono-dermo-skeletal syndrome. This is a phenocopy of Crouzon syndrome in association with acanthosis nigricans.…”