Atypical Clinical Course of Griscelli Syndrome Type 2 With Primarily Neurologic Presentation and Adult-Onset in a...

Griscelli Syndrome Type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic mutations in the RAB27A gene. Typically, it is characterized by cutaneous hypopigmentation, immunodeficiency, with or without neurological abnormalities secondary to hemophagocytic lymphohistiocytosis (HLH). Without treatment, GS2 often results in fatal outcomes within the first decade of life. Adult-onset GS2 is extremely rare, with few documented cases. We describe a 48-year-old patient with a neurological presentation: cerebellar dysarthria, ataxia, nystagmus, and muscle hypotonia in the lower limbs. Diagnostic workup included next-generation sequencing (NGS panel), clinical investigations, and segregation analysis in the family to confirm the diagnosis of GS2. Genetic testing revealed two variants in RAB27A: The likely pathogenic c.550C>T [p.(Arg184*)] and c.213G>T [p.(Gln71His)], a variant of uncertain significance. Clinical evaluation confirmed irregular hair pigmentation due to melanosome transport defect, low natural killer cell activity, cytopenia, hypertriglyceridemia, elevated serum ferritin, and brain tissue biopsy compatible with hemophagocytosis, thus cementing the clinical diagnosis of GS2. Segregation analysis confirmed the trans configuration of the variants. Based on the clinical and genetic evidence, the p.Gln71His variant was reclassified as likely pathogenic per ACMG criteria. This rare late-onset GS2 case highlights the need to consider GS2 in adult patients with atypical presentations. Early diagnosis is vital for effective intervention. Greater clinical awareness and research are needed to understand its phenotypic spectrum in adults.