A Novel Mutation Involving the Initiation Codon of FGF3 in a Family Described with Complete Inner Ear Agenesis, Microtia and Major Microdontia (LAMM Syndrome)

Elise Schaefer Maryline Minoux

doi:10.4172/2157-7412.1000251

Abstract

LAMM syndrome (OMIM #610706) is a rare autosomal recessive syndrome characterized by the association of Michel aplasia, microdontia and malformation of the external ear. Different mutations in FGF3 gene were reported in several families presenting with this syndrome. Clinical features and genetic results observed in a family with LAMM syndrome are reported. The diagnosis of isolated Michel aplasia was initially made in this family composed of two affected children. Microtia and microdontia was recently evidenced in both patients suggesting the diagnosis of LAMM syndrome. New auditory and orodental iconography was performed permitting to describe the patients’ phenotype in depth and to report rare findings of LAMM syndrome. The sequencing of FGF3 gene identified a novel missense mutation (c.2T>G), substituting the first initiator methionine in arginine, in the fibroblast growth factor 3 (FGF3) at the homozygous state in both patients. LAMM syndrome was confirmed and appropriate genetic counseling performed.

Highlights

Whereas developmental defects of ears and/or teeth are very common, the combination of both remains a rare syndromic event
Michel aplasia in association with microdontia and malformation of the external ear defines the LAMM syndrome (Labyrinthine Aplasia, Microtia, and Microdontia; OMIM 610706), which is a rare recessive syndrome recently related to mutations in the FGF3 gene
Haplotype sharing of SNPs identified a homozygote region of Mb on chromosome encompassing FGF3 gene, between rs 1944130 and rs 568421 corresponding to physical position of 69,291,704 - 78,714,313 bp (Figure 4B)

Summary

Introduction

Whereas developmental defects of ears and/or teeth are very common, the combination of both remains a rare syndromic event. First described in 1863 [1] is a very rare malformation with complete bony and membranous aplasia of the inner ear. Michel aplasia in association with microdontia and malformation of the external ear (microtia type I) defines the LAMM syndrome (Labyrinthine Aplasia, Microtia, and Microdontia; OMIM 610706), which is a rare recessive syndrome recently related to mutations in the FGF3 gene. A dozen of FGF3 mutations have been reported to date in various studies. Three different mutations were described in 3 unrelated Turkish families: p.Arg104*, p.Ser156Pro and p.Val206Serfs*13 [2]. 9 other mutations were reported in 6 different studies [3,4,5,6,7,8]

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