Does CMT1A homozygosity cause more severe disease with root hypertrophy and higher CSF proteins?

Abstract

Charcot-Marie-Tooth type 1A (CMT1A) is associated with a peripheral myelin protein-22 ( PMP22 ) gene duplication on chromosome 17p11.2.1 CMT1A patients have three PMP22 copies and a gene dosage effect, leading to increased PMP22 protein expression, is the hypothesized pathogenic mechanism. Homozygosity for the duplication has been reported in patients from three families, with both parents carrying the duplication and transmitting the mutation to their offspring, who had PMP22 tetrasomy and variable disease severity.1-3⇓⇓ We report a homozygous CMT1A patient with rather severe disease, high CSF proteins, and astonishing root hypertrophy. The patient is a 45-year-old man born to first-cousin parents. His parents, two sisters, one brother, and two sons had pes cavus and lower limb weakness (see figure E-1A on the Neurology Web site). He developed pes cavus and walking difficulties at age 11 years, scoliosis at age 16, and slowly progressive lower limb weakness until age 42, when he had more rapid worsening with difficulty climbing stairs, loss of balance, and hand weakness. Hearing loss started at age 33 years. On admission, he had marked foot deformities (walking with support), moderate scoliosis, bilateral hearing loss, muscle wasting and weakness (severe distally in lower …