P.126 - Spinal muscular atrophy with lower extremity predominance: a recognizable phenotype of BICD2 mutations in children

Abstract

Heterozygous bicaudal D homolog 2 gene (BICD2) mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED). We describe the clinical phenotype, imaging and pathological features in 2 children (a boy and a girl) with BICD2 related SMALED. The first child was born with lower limb arthrogryposis with marked contractures at hips, knees and ankles. She had marked lower limb wasting and weakness with mild scapular winging and weakness in the axial and shoulder muscles. Reflexes were absent in legs. She never achieved independent ambulation and now at the age of 16 years uses a powered chair for mobility. Her course has been non-progressive and complicated by several orthopaedic surgeries in her legs. She does not have any cognitive difficulties. Neurophysiology showed a classic neurogenic pattern. Muscle MRI at the age of 9 showed extensive bilateral and symmetrical fatty degeneration of all muscle groups in the thighs and the calves. She was identified to have a de novo c.565A > T p.(Ile189Phe) heterozygous pathogenic mutation in the BICD2 gene. In the second child, we identified a de novo BICD2 heterozygous variant, c.682G > T, p.Asp288Tyr with lower extremity dominant SMA phenotype. He had congenital foot deformity, muscle atrophy of the legs, and stable weakness mainly of ankle dorsiflexors and invertors. He is independently ambulant. He has brisk reflexes in the legs. There was no apparent sensory or brain dysfunction. A left Quadriceps muscle showed features of a classic neurogenic pattern. Leg muscle MRI showed bilateral atrophy within the vastus lateralis, rectus femoris, sartorius and deep biceps and in the legs, there was atrophy of the gastrocnemius and partial involvement of the tibialis anterior muscles bilaterally. These findings confirm the previously reported recognisable phenotype in children affected with SMALED due to BICD2 mutations. The presence of brisk reflexes in the context of neurogenic changes is of interest and is also observed in other types of SMALED.