A Boy Born Floppy With Severe Weakness and, Later, Contractures

This patient was initially evaluated elsewhere when he presented as a “floppy baby.” He was born at term of a 26-year-old primigravida; he was a 9-lb product of a 41-week gestation; the pregnancy was complicated by pyelonephritis. Respirations were normal at birth, but he was noted to be hypotonic and to have a weak cry. He was found to have torticollis at the age of 2 months. His scalp was mildly asymmetric; he was able to sit up at 5 months but could not pull himself up independently or raise his head against gravity at 2 years. He had never been able to walk.

MRI showed an increased signal on the T2-weighted image white matter. EKG and EEG were normal.

Family history was positive for porphyria in a cousin, a maternal grandfather, and a great-grandfather, and a first cousin of the mother had Charcot–Marie–Tooth disease.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Ulnar Nerve R.	Normal ≤ 3.5	Normal ≥ 5.6	Normal ≥ 49
Wrist	2.0	6	–
Above elbow	3.6	6	51

Peroneal Nerve R.	Normal ≤ 5.7	Normal ≥ 2.2	Normal ≥ 41
Ankle	3.2	3	–
Knee	6.4	2.6	47

F-Wave Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Ulnar nerve R.	25.1	31
Peroneal nerve R.	42.0	52

EMG Data

Muscle	Insrt Activity	Fibs	Pos Waves	Fasc	Amp	Dur	Poly	Pattern
Vastus lateralis R.	Norm	None	None	None	Low	Brief	Many	Full
Tibialis anterior R.	Norm	None	None	None	Low	Norm	None	Full
Deltoid R.	Norm	None	None	None	Low	Brief	Many	Full
Biceps brachii R.	Norm	None	None	None	Norm	Brief	Many	Full
First dorsal interosseous R.	Norm	None	None	None	Norm	Norm	None	Full

What were the EMG Findings?

Nerve conduction tests were normal. EMG demonstrated “myopathic changes” with many polyphasic motor unit action potentials. Serum creatine kinase (CK) was 1225 IU/L (normal, <200 IU/L). Left quadriceps biopsy showed “marked variation of fiber size, internalized nuclei, hypertrophic fibers, and no ragged red fibers.” Histochemistry was reported as normal. He was diagnosed as having a congenital muscular dystrophy.

At the age of 2½ years his general physical examination and intellectual function appeared normal. He had contractures of the left elbow at about 20 degrees and had a limited range of motion of the ankles. The joints were normal. He was alert and responded properly to questions. Cranial nerves were normal except for mild bilateral facial weakness. There was diffuse hypotonia with wasting in the elbows. Reflexes were absent throughout. Pain perception appeared normal.

At the age of 14 years he had evidence of severe weakness with contractures and developed respiratory failure requiring tracheostomy ( Fig. 86-1 ). He also developed staring spells and had generalized tonic/clonic seizures. EEG showed frontal sharp waves on the right side.

What is the Differential Diagnosis?

This patient presented as a floppy baby. The differential diagnosis of this includes spinal muscular atrophy, but the lack of fasciculations and denervation on the EMG is against this disease. The lack of significant facial weakness and ptosis are against congenital myasthenic syndrome. The differential diagnosis should include central core, disease, nemaline myopathy, and myotubular myopathy that are unlikely because of the rather high serum CK, but this can be seen in congenital muscular dystrophy and congenital myotonic dystrophy. Acid maltase deficiency was a consideration, as this patient presented with only weakness and hypotonia, unlike the infantile form of Pompe disease, which also manifests with visceromegaly. The lack of myotonia on EMG is against this diagnosis. There was no evidence of a neuropathy.

Some mitochondrial myopathies could have similar MRI findings, but the reported absence of ragged red fibers in the biopsy is against this diagnosis.

A quadriceps muscle biopsy showed dystrophic changes with proliferation of endomysial connective tissue and fat with lack of merosin staining ( Fig. 86-2 ).

The MRI was reviewed and this showed diffuse white matter changes on T2-weighted images ( Fig. 86-3 ). The MRI and biopsy findings are diagnostic of merosin-deficiency congenital muscular dystrophy. ( Figs. 86-4 to 86-9 show patients and biopsy findings of various other congenital myopathies.)

Discussion

This patient was evaluated in early childhood for severe weakness and hypotonia and later at the age of 14 years when he presented with seizures. He was diagnosed as having congenital muscular dystrophy (CMD) with merosin deficiency.

Several forms of CMD have been reported since the initial description by Batten in 1903 ( Table 86-1 ). Some of these might present with severe mental retardation. The most common form of CMD is caused by a deficiency of laminin α-2, or merosin (CMD 1A), as in this patient. This occurs in up to 50% of the cases. It has an incidence of 1:30,000. The clinical characteristics of CMD 1A are relatively uniform in those with severe disease, caused by complete absence of the protein. They manifest early, even during pregnancy, with diminished fetal movement and may require respiratory support at birth. Patients could have facial muscle weakness, but the extraocular muscles are not affected. The weakness in limb muscles is more proximal than distal. There is muscle atrophy and joint contractures but no muscle hypertrophy. A partial merosin deficiency might cause hypotonia and delayed motor milestones, but many patients can remain ambulatory and even appear normal in adulthood or have a very mild limb-girdle syndrome.

Table 86-1

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