[source]
pmid = PMID:24239060
title = Novel TPM3 mutation in a family with cap myopathy and review of the literature
[diagnosis]
disease_id = OMIM:609284
disease_label = Congenital myopathy 4B, autosomal recessive
[text]
The index patient (II.2; Fig. 1B and D) is a 45-year-old
woman, who developed a mild proximal muscle weakness
since early childhood. She never crawled and started to
walk at the age of 2 years. She fell frequently and
performed poorly at school sports. She suffered from mild
progressive scoliosis since the age of 13 years (Fig. 1D).
At the age of 45 years, she presented with a waddling gait
and a mild proximal and distal lower limb weakness,
resulting in problems to run and difficulties to climb the
stairs. She walked unassisted without distance limitation.
She had no myalgia, myoglobinuria, diplopia, dysarthria
or dysphagia. Pulmonal infections or signs of respiratory
insufficiency did not occur. The clinical neurological
examination revealed generalized muscle hypotrophy and
a body mass index (BMI) of 17.2. The index patient
presented a long narrow face, high arched palate, discrete
micrognathia (Fig. 1B), scoliosis and scapula alata
(Fig. 1D). She did not present facial weakness,
ophthalmoparesis, or ptosis. She could not walk on the
heels, while toe walking was normal. The patient did not
present a Gowers’ sign. Muscle strength was
symmetrically decreased in the neck flexors (MRC 4/5),
deltoid (4/5), biceps brachii (4/5), hamstrings (4/5), foot
extensors (4/5) and foot supination and pronation (4/5)
muscles. The index patient did not have foot deformities.
Deep tendon reflexes were weak or absent. Touch and
vibration sense were unremarkable.
The muscle biopsy of the index patient (left quadriceps
femoris muscle; 34 years; performed 11 years prior to her
first presentation at our neurological department) showed
cap-shaped, bluish subsarcolemmal inclusions in 6% of
the fibres on mGT (Fig. 3A), that were slightly
eosinophilic on HE (Fig. 3B). The caps comprised up to
50% of the muscle fibre at transverse sections. Myosin
ATPase reactivity was reduced in the cap areas (Fig. 3C
and D). The cap structures were darkly stained on
NADH-TR (Fig. 3E) and were not detectable on periodic
acid-Schiff (PAS) staining. The myosin ATPase stains
revealed type 1 fibre predominance. Numerous atrophic
fibres and nuclear bags were observed. The endomysial
connective tissue was not increased. Rare myophagic
reactions in muscle fibres were present, while
inflammatory infiltrates were absent.
In the index
patient, MRI revealed symmetrical fatty infiltration in
paraspinal muscles (Fig. 2C), gluteus maximus and
minimus (Fig. 2E), semimembranosus and biceps femoris
muscles (Fig. 2G), and less pronounced in soleus and
tibial anterior muscles (Fig. 2I). .
Serum CK levels were examined in patients II.2 and III.1
and were normal.