Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A-evidence for "double trouble" overlapping syndromes

Background: We report on a patient with genetically confirmed
overlapping diagnoses of CMT1A and FSHD. This case adds to the
increasing number of unique patients presenting with atypical
phenotypes, particularly in FSHD. Even if a mutation in one disease
gene has been found, further genetic testing might be warranted in
cases with unusual clinical presentation. Case presentation: The
reported 53 years old male patient suffered from walking
difficulties and foot deformities first noticed at age 20. Later
on, he developed scapuloperoneal and truncal muscle weakness, along
with atrophy of the intrinsic hand and foot muscles, pes cavus,
claw toes and a distal symmetric hypoesthesia. Motor nerve
conduction velocities were reduced to 20 m/s in the upper
extremities, and not educible in the lower extremities, sensory
nerve conduction velocities were not attainable. Electromyography
showed both, myopathic and neurogenic changes. A muscle biopsy
taken from the tibialis anterior muscle showed a mild myopathy with
some neurogenic findings and hypertrophic type 1 fibers. Whole-body
muscle MRI revealed severe changes in the lower leg muscles,
tibialis anterior and gastrocnemius muscles were highly replaced by
fatty tissue. Additionally, fatty degeneration of shoulder girdle
and straight back muscles, and atrophy of dorsal upper leg muscles
were seen. Taken together, the presenting features suggested both,
a neuropathy and a myopathy. Patient's family history suggested an
autosomal dominant inheritance. Molecular testing revealed both, a
hereditary motor and sensory neuropathy type 1A (HMSN1A, also
called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22
gene duplication and facioscapulohumeral muscular dystrophy (FSHD)
due to a partial deletion of the D4Z4 locus (19 kb). Conclusion:
Molecular testing in hereditary neuromuscular disorders has led to
the identification of an increasing number of atypical phenotypes.
Nevertheless, finding the right diagnosis is crucial for the
patient in order to obtain adequate medical care and appropriate
genetic counseling, especially in the background of arising
curative therapies.