Torpedo Maculopathy Associated with NEXMIF Mutation.

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Mutations in the neurite extension and migration factor (NEXMIF) gene are linked to X-linked intellectual disability.
• Previously reported males with NEXMIF mutations exhibit intellectual disability, autistic features, speech impairment, epilepsy, facial dysmorphism, and strabismus.
• Females with NEXMIF mutations typically present with milder intellectual disability and severe, drug-resistant epilepsy.

Purpose of the Study:

• To report a novel pathogenic variant in the NEXMIF gene.
• To describe the clinical phenotype associated with this new variant.
• To investigate potential roles of NEXMIF in ocular development.

Main Methods:

• Case report of a 32-month-old boy with a novel de novo frameshift NEXMIF pathogenic variant (p.Glu375ArgfsX21).
• Clinical assessment including neurological examination, developmental assessment, and ophthalmologic evaluation.
• Literature review of previously reported cases with NEXMIF mutations and ophthalmologic abnormalities.

Main Results:

• The patient presented with mild motor delay, language delay, autistic features, and strabismus.
• A novel de novo frameshift NEXMIF pathogenic variant (p.Glu375ArgfsX21) was identified.
• Fundus examination revealed torpedo maculopathy, a rare ophthalmologic abnormality not previously reported in association with NEXMIF mutations.
• Literature review indicated other ophthalmologic abnormalities in 7 out of 15 males with NEXMIF mutations.

Conclusions:

• This case expands the phenotypic spectrum of males with NEXMIF mutations.
• The presence of torpedo maculopathy suggests a potential role for NEXMIF in ocular development.
• Further research is warranted to elucidate the function of NEXMIF in the nervous and ocular systems.