Genetic Myopathy Masquerading as Motor Neuron Disease

Document Type

Conference Proceeding - Restricted Access

Publication Date

5-9-2025

Abstract

The myotilin gene (MYOT) encodes a Z-disk protein linking neighboring sarcomeres to form myofibrils. Z protein is expressed in skeletal and cardiac muscle. Mutations in MYOT gene have been originally associated with different disorders including limb-girdle muscular dystrophy, myofibrillar myopathy, and spheroid body myopathy. It mostly affects distal limb and facial muscles.

A 75-year-old male was evaluated in the neuromuscular clinic for slowly progressive distal limb weakness started around age 70 as right foot drop and later progressed to right distal arm weakness and mild dysphagia within 2-3 years. There were no associated sensory symptoms, cramping, fasciculations or pain. Patient endorsed long standing "skinny ankles and wrists" in himself and mother. Examination revealed marked dorsal predominant forearm and distal legs atrophy along with asymmetric weakness in wrist/finger extension, thumb/finger abduction, hip flexion and ankle dorsiflexion. While his general neurologist initially suspected ALS due to the age of symptom onset, progressive asymmetric weakness and dysphagia without sensory symptoms or elevation in CK, we suspected genetic myopathy instead of ALS due to wrist/finger extension weakness, positive family history, lack of UMN signs and absent fasciculations despite significant atrophy.

Nerve conduction study showed low CMAP in the median, ulnar and radial responses without conduction block or demyelinating changes. Lower extremity motor responses and all sensory responses were normal. EMG of the clinically weak muscles showed positive sharp waves, fibrillation potentials, CRD/myotonic-like discharges, and myopathic>neurogenic motor units, consistent with a distal irritative myopathy. Genetic testing revealed MYOT mutation.

Slowly progressive muscle weakness with normal CK in elderly patients often raise concern for degenerative and fatal process like motor neuron disease. However, genetic causes are not considered as frequently. We present a case of slowly progressive distal extensor predominant weakness in an elderly patient due to myofibrillar myopathy secondary to MYOT gene mutation. Mutations in 6 genes are associated with myofibrillar myopathy. DES, MYOT and LDB3 genes are most common. EMG/NCS along with the genetic testing can aid in the diagnosis.

Comments

2025 Research Day Corewell Health West, Grand Rapids, MI, May 9, 2025. Abstract 1668

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