Severe ADEM-Like Neuroinflammatory Disease and Cerebrovascular Fragility With Recurrent Pseudoaneurysms and Moyamoya in a Familial Germline CBL Mutation: Expanding the Clinical Phenotype.
Michal Bar-Hakim, Anat Abramovich, Sara Via-Dorembus et al.
✦ AI-curated · Sources linked
Case in brief
Two sisters with the same paternally inherited germline CBL variant had markedly different presentations. The older, previously healthy 4-year-old developed rapidly progressive ADEM-like neuroinflammation after a febrile illness, with optic neuritis and severe dystonia-parkinsonism. MRI showed extensive basal ganglia and white-matter abnormalities without moyamoya; cerebrospinal fluid showed pleocytosis and elevated protein, while infectious and metabolic investigations were negative. Her younger sister had JMML and later recurrent bilateral arterial ischemic strokes with severe bilateral moyamoya. She developed radial and femoral artery pseudoaneurysms after vascular procedures. Bilateral encephaloduroarteriosynangiosis was followed by clinical stabilization.
What made this case unusual
The siblings’ divergent phenotypes included severe ADEM-like neuroinflammation without moyamoya in one, and moyamoya with profound systemic vascular fragility and recurrent procedure-associated peripheral arterial pseudoaneurysms in the other.
Diagnostic / clinical pearl
In a patient with a germline CBL variant, severe neuroinflammation or vascular fragility may accompany the recognized hematologic and moyamoya manifestations; the siblings’ contrasting presentations illustrate the breadth of the reported phenotype.
Why it matters
The report broadens the described clinical spectrum of CBL-related disorders to include central nervous system immune dysregulation and systemic vascular fragility.