A Rare Instance of Concordant Charcot-Marie-Tooth Disease and Familial Partial Lipodystrophy Type 2

Lamin A/C (LMNA)-related laminopathies can involve adipose tissue, peripheral nerves, skeletal muscle, and the heart. We report a 65-year-old woman with a seven-year history of progressive distal sensorimotor neuropathy, burning pain in both feet, loss of hand dexterity, and worsening steppage gait. Physical examination demonstrated distal intrinsic hand and foot atrophy, absent reflexes, distal sensory loss, pes cavus, claw and hammer toe deformities, hindfoot varus, limb lipoatrophy, and relative cervicofacial/central adiposity. Electromyography and nerve conduction studies (EMG/NCS) showed a length-dependent, axonal-predominant mixed sensorimotor polyneuropathy consistent with a hereditary neuropathy and Charcot-Marie-Tooth (CMT)-like phenotype. Genetic testing identified a heterozygous pathogenic lamin A/C variant consistent with familial partial lipodystrophy type 2 (FPLD2); exact variant nomenclature was not available in the records accessible to the authors. Available metabolic data showed impaired fasting glucose, with glucose at 109 mg/dL and hemoglobin A1c (HbA1c) at 5.6%, while triglycerides and low-density lipoprotein (LDL) cholesterol were controlled at 139 mg/dL and 54 mg/dL, respectively. Fasting insulin, C-peptide, and homeostatic model assessment for insulin resistance (HOMA-IR) were not available; therefore, the available data support dysglycemia and increased metabolic risk rather than definitive biochemical confirmation of severe insulin resistance. Management included custom orthopedic footwear with supramalleolar orthotic (SMO) inserts, endurance-focused physical therapy, gabapentin for neuropathic pain, metformin for dysglycemia, atorvastatin for lipid and atherosclerotic cardiovascular disease (ASCVD) risk reduction, antihypertensive therapy for blood-pressure control, and longitudinal cardiac surveillance with electrocardiogram (ECG), echocardiography, and ambulatory rhythm monitoring. This case highlights the multisystem nature of LMNA-related disease and the importance of recognizing overlapping adipose, neurologic, metabolic, and cardiac manifestations as part of a unified disease process requiring coordinated neuromuscular, endocrine, and cardiology follow-up.