These findings describe, for the first time, variable inner ear malformations and outer ear dysplasia in the presence of constant microdontia, associated with homozygous inheritance of the p.R95W mutation in FGF3, mirroring phenotypes observed in mouse models ablating FGF3/FGFR2 signaling.
Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706 - LAMM).
We report on the first cases of FGF3 compound heterozygotes in two European families from non-consanguineous marriages, affected with labyrinthine aplasia, microtia, and microdontia (LAMM) Syndrome.
Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3).
Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.
Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia.
In conclusion, this study has demonstrated that Trps1 is a positive regulator of cell proliferation in both dental mesenchyme and epithelium, suggesting that the microdontia in TRPS is likely due to decreased cell proliferation in developing tooth organs.
They also show that WNT10B variants are associated not only with oligodontia and isolated tooth agenesis, but also with microdontia, short tooth roots, dental pulp stones, and taurodontism.
Clinical characterization of families segregating a PAX9 mutation reveal that all affected individuals were missing the mandibular second molar and their maxillary central incisors are most susceptible to microdontia.
We found that Tbx1 conditional knockout (Tbx1(cKO)) mice featured microdontia, which coincides with decreased stem cell proliferation in the LaCL of Tbx1(cKO) mice.
We also excluded in our family the SMOC2 gene (Sparc Related Modular Calcium Binding Protein 2) which was recently identified as a causal gene in dentin dysplasia type I with microdontia and misshapen teeth.
This is the second report describing SMOC2 mutations with oligodontia and microdontia underlining the key role for this signalling molecule in tooth development.
The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia.
Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706 - LAMM).
In the case-control data, clefts, supernumerary teeth and familial cancer history were associated with ABCA4-rs481931 on chromosome 1 (p = 2E-19, 0.0007, 2E-06, respectively), and clefts and microdontia were associated with rs1325474 on chromosome 6 (p = 1E-06, 0.0002, respectively).