Phenotypic variability in two siblings with Poretti-Boltshauser syndrome.

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Poretti-Boltshauser Syndrome (PBS) is a rare autosomal recessive neuro-ophthalmological disorder.
• Characterized by cerebellar ataxia, developmental delay, intellectual disability, and vision abnormalities.
• Caused by mutations in the LAMA1 gene, often leading to cerebellar abnormalities like cysts.

Observation:

• Presents two siblings with LAMA1 mutations and differing clinical manifestations.
• One sibling displayed cerebellar dysplasia with cysts and oculomotor apraxia.
• The other sibling showed milder cerebellar dysplasia without cysts, alongside a macular hole.

Findings:

• Demonstrates significant intrafamilial phenotypic variability in PBS.
• Highlights that cerebellar cysts may not be present in all LAMA1 mutation cases.
• Identifies distinct oculomotor and macular abnormalities associated with PBS.

Implications:

• Underscores the need for comprehensive clinical evaluation in PBS.
• Emphasizes the importance of genetic testing for accurate diagnosis and management.
• Suggests LAMA1 mutations can lead to a broader spectrum of neuro-ophthalmological presentations than previously recognized.