Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia

Clinical characteristics: Congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) is characterized by: profound bilateral congenital sensorineural deafness associated with inner ear anomalies (most often bilateral complete labyrinthine aplasia); microtia (type I) that is typically bilateral (although unilateral microtia and normal external ears are observed on occasion); and microdontia (small teeth). Individuals with LAMM syndrome commonly have motor delays during infancy presumably due to impaired balance from inner ear (vestibular) abnormalities. Growth, physical development, and cognition are normal.

Diagnosis/testing: The diagnosis of LAMM syndrome is established in a proband by identification of biallelic pathogenic variants in FGF3 on molecular genetic testing.

Management: Treatment of manifestations: Enrollment in appropriate early-intervention programs and educational programs for the hearing impaired; consideration of vibrotactile hearing devices or brain stem implants for individuals with complete labyrinthine aplasia; consideration of cochlear implantation for those with a cochleovestibular nerve and a cochlear remnant; routine ophthalmologic management of strabismus.

Prevention of secondary complications: Attention to the increased risk for accidents secondary to delayed gross motor development and deafness.

Surveillance: Yearly evaluations with a physician familiar with LAMM syndrome or other forms of hereditary deafness; regular ENT and dental evaluations.

Agents/circumstances to avoid: Individuals with residual cochlear function should avoid noise exposure. Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution.

Evaluation of relatives at risk: It is recommended that sibs have hearing screening to allow early diagnosis and treatment of hearing impairment.

Genetic counseling: LAMM syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FGF3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.