Udd Distal Myopathy – Tibial Muscular Dystrophy

Clinical characteristics: Udd distal myopathy – tibial muscular dystrophy (UDM-TMD) is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 30 years. Disease progression is slow and muscle weakness remains confined to the anterior compartment muscles for many years. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, UDM-TMD can remain unnoticed even in the elderly. EMG shows profound myopathic changes in the anterior tibial muscle, but preservation of the extensor brevis muscle. Muscle MRI shows selective fatty degeneration of the anterior tibial muscles and other anterior compartment muscles of the lower legs. Serum CK concentration may be normal or slightly elevated. Muscle biopsy shows progressive dystrophic changes in the tibialis anterior muscle with rimmed vacuoles at the early stages and replacement with adipose tissue at later stages of the disease.

Diagnosis/testing: The diagnosis of UDM-TMD is established in a proband with typical clinical findings and the identification of a heterozygous pathogenic variant in the last exon of TTN by molecular genetic testing.

Management: Treatment of manifestations: Orthotic devices for the foot drop; tibial posterior tendon transposition to replace lost ankle dorsiflexion function when foot drop is severe before age 55.

Surveillance: Neuromuscular examination every one to four years to evaluate disease progression and need for rehabilitation and orthotic treatment.

Agents/circumstances to avoid: Heavy muscle force training of weak muscles.

Genetic counseling: UDM-TMD is inherited in an autosomal dominant manner. Most individuals diagnosed with UDM-TMD have an affected parent. Each child of an individual with UDM-TMD has a 50% risk of inheriting the TTN pathogenic variant. If the reproductive partner of a proband is also heterozygous for a UDM-TMD TTN pathogenic variant (a situation more likely to be seen in Finland and/or in reproductive partners of Finnish heritage – due to a founder effect), offspring are at risk for the early-onset severe limb-girdle muscular dystrophy phenotype associated with biallelic TTN pathogenic variants. Once the TTN pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk and preimplantation genetic testing are possible.