Clinical spectrum of BICD2 mutations.

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Mutations in the BICD2 gene are linked to autosomal dominant lower extremity-predominant spinal muscular atrophy 2A (SMALED2A).
• SMALED2A is characterized by a distinct pattern of muscle involvement in the thigh and calf, observable via MRI.
• While minor sensory impairment is sometimes reported, objective sensory deficits remain unconfirmed.

Purpose of the Study:

• To identify and characterize new mutations in the BICD2 gene.
• To further define the muscle involvement patterns in SMALED2A using MRI.
• To investigate potential sensory neuropathy in SMALED2A patients.

Main Methods:

• Clinical data collection from 11 patients across five families with BICD2 mutations.
• Genetic diagnosis through gene panel testing.
• Skin biopsies for epidermal nerve fiber density analysis in two patients.

Main Results:

• Three novel pathogenic BICD2 mutations were identified, alongside the previously known p.Ser107Leu mutation.
• Lower limb weakness and foot deformities were common clinical presentations.
• Muscle MRI revealed consistent fat deposition patterns, notably in pelvic, thigh, and calf muscles, with relative sparing of intrinsic foot muscles.
• One patient showed clinical and electrophysiological sensory impairment; another exhibited small-fiber neuropathy confirmed by skin biopsy.

Conclusions:

• Three new pathogenic BICD2 mutations expand the known mutation spectrum for SMALED2A.
• Muscle MRI findings confirm a specific pattern of muscle involvement in SMALED2A, offering detailed insights into pelvic, thigh, and calf muscle pathology.
• The study provides evidence suggesting the possibility of sensory involvement, including small-fiber neuropathy, in SMALED2A.