Demonstrating clinical and radiological variability of adult-onset Alexander disease in three siblings.

UNLABELLED: Adult-onset Alexander disease (AOAD) is a genetic neurodegenerative disease due to mutations in GFAP, often causing medullary degeneration.

OBJECTIVES

(i) In a kindred of three siblings with AOAD to compare and correlate clinical progression with MRI quantified medullary atrophic changes. (ii) To demonstrate how AOAD risks under-diagnosis in an older patient population.

METHODS

We retrospectively compared three siblings in their fifth and sixth decade from a family of Irish heritage with AOAD with respect to clinical phenotype, radiological measurements and delay to diagnosis.

RESULTS

Three siblings (∼60 years of age) harboring a relatively rare GFAP variant p.Ser385Cys presented insidiously with variable degree of motor, cerebellar and autonomic dysfunction. MR imaging demonstrated differences in volume and AP diameter of the medulla oblongata among the siblings, approximately correlating with severity of symptom presentation and showing progression over time.

DISCUSSION: Insidious onset of symptoms led to delay in diagnosis. Serial and detailed MRI surveillance of lower brainstem and upper cervical spine is a valuable biomarker, that can correlate with symptom severity and progression.