LAMM syndrome: two new patients with a novel mutation in FGF3 gene and additional clinical findings

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel’s aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations.

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“…Cases are detailed from [2,8,9,10,11,12,13,14,15]. A—Asymmetrical, S—Symmetrical, T1M0—Type 1 Microtia, SWS—Small widely spaced, Fam-Family.…”

Section: Figurementioning

confidence: 99%

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases

Yassin

D’Arco

Morín

et al. 2019

Genes

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Identification of a homozygous frameshift mutation in the FGF3 gene in a consanguineous Iranian family: First report of labyrinthine aplasia, microtia, and microdontia syndrome in Iran and literature review

Jamshidi

Shokouhian

Mohseni

et al. 2023

Molec Gen & Gen Med

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Background To date, over 400 syndromes with hearing impairment have been identified which altogether constitute almost 30% of hereditary hearing loss (HL) cases around the globe. Manifested as complete or partial labyrinthine aplasia (severe malformations of the inner ear structure), type I microtia (smaller outer ear with shortened auricles), and microdontia (small and widely spaced teeth), labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome (OMIM 610706) is an extremely rare autosomal recessive condition caused by bi‐allelic mutations in the FGF3 gene. Methods Using the whole‐exome sequencing (WES) data of the proband, we analyzed a consanguineous Iranian family with three affected members presenting with congenital bilateral HL, type I microtia, and microdontia. Results We discovered the homozygous deletion c.45delC in the first exon of the FGF3 gene, overlapping a 38.72 Mb homozygosity region in chromosome 11. Further investigations using Sanger sequencing revealed that this variant co‐segregated with the phenotype observed in the family. Conclusion Here, we report the first identified case of LAMM syndrome in Iran, and by identifying a frameshift variant in the first exon of the FGF3 gene, our result will help better clarify the phenotype–genotype relation of LAMM syndrome.

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Neuroanatomical anomalies due to a defect in the FGF3 gene, associated with the Labyrinthine Aplasia, Microtia and Microdontia syndrome: insights from the placement of auditory brainstem implants in two siblings

Frijns,

Geerders,

Scholing

et al. 2024

Therapeutic Advances in Rare Disease

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Here, we describe two congenitally deaf male siblings with the same compound heterozygotic, likely pathogenic mutations in the FGF3 gene, associated with the labyrinthine aplasia, microtia and microdontia (LAMM) syndrome. Both children had bilateral cochleovestibular aplasia, precluding cochlear implantation. The elder brother received an auditory brainstem implant (ABI) with very limited auditory responses. During the ABI-surgery of the younger subject, it was discovered that excellent auditory responses could be obtained when the electrode array was placed considerably more caudally and more medially than standard. It was observed that the foramen of Luschka, the entrance to the lateral recess of the fourth ventricle was located more caudally. In view of this observation the good auditory development of the latter child, it was decided to give the older child a contralateral ABI. Again, it turned out that the anatomy of the brainstem was abnormal with a more caudal location of the foramen of Luschka and the cochlear nucleus, and this child is showing good progress with his auditory development. It is concluded that one should be aware of the anatomical differences at the level of the brainstem when placing an ABI in children with this genetic disorder (and most likely also in the LAMM syndrome). This also underpins the need of a multidisciplinary approach with closely collaborating team members and good family guidance when diagnosing and treating children with rare deafness.

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LAMM syndrome: two new patients with a novel mutation in FGF3 gene and additional clinical findings

Cited by 6 publications

References 11 publications

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases

Identification of a homozygous frameshift mutation in the FGF3 gene in a consanguineous Iranian family: First report of labyrinthine aplasia, microtia, and microdontia syndrome in Iran and literature review

Neuroanatomical anomalies due to a defect in the FGF3 gene, associated with the Labyrinthine Aplasia, Microtia and Microdontia syndrome: insights from the placement of auditory brainstem implants in two siblings

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