Clinical characteristics: Aymé-Gripp syndrome is classically defined as the triad of bilateral early cataracts, sensorineural hearing loss, and characteristic facial features in combination with neurodevelopmental abnormalities. The facial features are often described as "Down syndrome-like" and include brachycephaly, flat facial appearance, short nose, long philtrum, narrow mouth, and low-set and posteriorly rotated ears. Hearing loss is often congenital. Other features may include postnatal short stature, seizure disorder, nonspecific brain abnormalities on head imaging, skeletal abnormalities, and joint limitations. A subset of individuals have been found to have pericarditis or pericardial effusion during the neonatal or infantile period. All affected individuals have had developmental delay, but the degree of cognitive impairment is extremely variable. Other features including gastrointestinal and endocrine abnormalities, ectodermal dysplasia (i.e., nail dystrophy and mammary gland hypoplasia), dental anomalies, and chronic glomerulopathy with proteinuria have been reported in rare affected individuals.
Diagnosis/testing: The diagnosis of Aymé-Gripp syndrome is established in a proband with cataracts, sensorineural hearing loss, and suggestive facial features and a heterozygous pathogenic variant in a specific region of MAF identified by molecular genetic testing.
Management: Treatment of manifestations: Treatment is symptomatic and ideally involves multidisciplinary care. Hearing aids or cochlear implant for sensorineural hearing loss; surgical intervention and eye glasses for cataracts and refractive errors, respectively; physical therapy for milder joint limitations; hip replacement for those with chondrolysis; standard therapy for developmental delay / cognitive impairment, seizure disorder, scoliosis, congenital heart defects / pericardial issues, oligodontia, and hypothyroidism.
Surveillance: Dental evaluation every six months; assessment for new neurologic manifestations, progressive joint restriction in major joints, and developmental and educational needs at each visit; clinical examination for scoliosis at each visit until skeletal maturity; at least annual audiology and ophthalmology evaluations; assessment of thyroid function as clinically indicated.
Genetic counseling: Aymé-Gripp syndrome is inherited in an autosomal dominant manner. Almost all individuals reported to date have been simplex cases (i.e., a single occurrence in a family) resulting from a de novo pathogenic variant. Once the causative genetic alteration has been identified in the proband, parental testing may be offered. Each child of an individual with Aymé-Gripp syndrome has a 50% chance of inheriting the MAF pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant in an affected family member is known.
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