No abstract

Neuromuscular Disorders 31 (2021) S47-S162 paresis is common. We describe a male patient presenting clinically at 2 years of age with toe-walking. His subsequent course was characterized by progressive distal weakness and loss of ambulation. Electromyelogram and nerve conduction studies demonstrated axonal injury in both sensory and motor nerves, affecting lower greater than upper extremities. Invitae Comprehensive Neuropathies Panel identified a known pathogenic variant in GDAP1 , c.116delA (p.Lys39Argfs * 5) as well as a Variant of Uncertain Significance (VUS) in GDAP1 , c.393G > C (p.Leu131Phe). Familial testing confirmed that GDAP1 variants were inherited (one from each unaffected parent). The patient regained ambulation after bilateral tendon lengthenings (Achilles, posterior tibial and intramuscular flexor digitorum longus (FDL)) and tenotomies (toe flexor, distal flexor hallucis longus, FDL 2-5). At recent clinic visit (age 5 years), motor function continued to improve. His speech has been unaffected to date. This case of compound heterozygous variants in GDAP1 causing Charcot-Marie-Tooth Disease, supports reclassifying c.393G > C (p.Leu131Phe) from VUS to likely pathogenic. It also provides additional insights regarding the natural history of GDAP1 -related CMT.