Childhood Ayme-Gripp syndrome: A case report

Area of Science:

• Genetics
• Rare Diseases
• Clinical Case Study

Background:

• Ayme-Gripp syndrome is an ultra-rare genetic disorder linked to mutations in the musculoaponeurotic fibrosarcoma (MF) gene.
• Phenotypic expression of MF gene mutations can be highly variable, impacting multiple organ systems.

Purpose of the Study:

• To present a detailed clinical case of a 12-year-old boy diagnosed with Ayme-Gripp syndrome.
• To document a novel pathogenic variant in the MF gene and its associated severe phenotype.
• To expand the understanding of MF gene-related disorders through deep phenotyping.

Main Methods:

• Detailed clinical case report of a pediatric patient.
• Genetic analysis to identify pathogenic variants in the musculoaponeurotic fibrosarcoma gene.
• Comprehensive phenotyping, including anthropometric, neurological, audiological, and radiological assessments.

Main Results:

• Identification of a pathogenic c.176C>A (p.Pro59His) variant in the MF gene.
• The patient exhibited the most severe short stature reported to date.
• Previously underreported features, including epileptic seizures, were observed alongside classic Ayme-Gripp syndrome manifestations (hearing loss, intellectual disability, craniofacial/skeletal malformations).
• Epilepsy was successfully managed with sodium valproate.

Conclusions:

• This case underscores the significant phenotypic variability of Ayme-Gripp syndrome and MF gene mutations.
• Deep phenotyping is crucial for characterizing ultra-rare genetic disorders.
• Early diagnosis and supportive care, including anticonvulsant therapy, are vital for managing Ayme-Gripp syndrome.