Dados do Trabalho

Título

Adult-onset Charcot-Marie-Tooth disease due to SAMD9L gene variant

RESUMO

Case presentation: A 49-year-old Brazilian woman presented with lower limb weakness for 8 years, associated with tingling and sensory disturbance in both hands and feet. Medical history disclosed chronic diarrhea, self-limited episodes of blurred vision and abdominal pain mimicking appendicitis. Family history was unremarkable. Her cognitive function and general development were normal. Examination revealed inability to perform tandem gait, positive Romberg test, pes cavus, diplopia during bilateral horizontal gaze. Reduced deep tendon reflexes in upper limbs and brisk reflexes in lower limbs. Paraparesis (predominantly distal). Muscle biopsy disclosed mild subsarcolemmal mitochondrial proliferation and nonspecific chronic neurogenic amyotrophy. Nerve conduction studies disclosed distal and uniform demyelinating sensorimotor polyneuropathy. Brain MR imaging disclosed mild leukoencephalopathy, mild cerebellar atrophy, and the hot-cross bun sign. Laboratory tests revealed normal values. Whole-exome sequencing disclosed a heterozygous pathogenic variant in the SAMD9L gene.
Discussion: Variants in Sterile Alpha Motif Domain-Contain Protein 9-Like (SAMD9L) gene have been associated with ataxia-pancytopenia syndrome (ATXPC), spinocerebellar ataxia type 49, myelodysplasia and leukemia syndrome with monosomy 7, and SAMD9L-associated autoinflammatory disease. The main clinical presentation in our case is a late-onset inherited demyelinating neuropathy, mimicking features of Charcot-Marie-Tooth (CMT) disease. Despite the presence of mild cerebellar atrophy, our patient presented mainly with sensory ataxia and her other clinical features resulted from chronic neuropathic compromise.
Final comments: Our report provides new evidence linking SAMD9L variants to primary peripheral nerve compromise, expanding the clinical spectrum associated with this gene. SAMD9L variants must be included in the differential diagnosis of late-onset demyelinating CMT phenotypes.

Palavras Chave

Charcot-Marie-Tooth; SAMD9L gene