Congenital muscular dystrophy type 1A (MDC1A) is an autosomal recessive disorder characterized by hypotonia, elevated serum creatine kinase level, delayed motor milestones, white matter changes observed by brain magnetic resonance imaging, and normal intelligence. A mutation in the laminin α2 (
Congenital muscular dystrophy type 1A (MDC1A) was first described in 1994 as a variant form of classic congenital muscular dystrophy (CMD)
The patient was born at 38 weeks of gestation with a birth weight of 3,500 gm. There was no history of decreased fetal movement and asphyxia at birth. She was a second child, with one 4-year-old brother with no medical problems. There was no history of parental consanguinity. She was healthy at birth, but her parents noticed that she had a delayed motor milestone at the age of 4 months as indicated by her inability to fully control her head. She was brought to Severance Children's Hospital for the first time at the age of 4 months and was hypotonic at that time. The traction test showed headlag, and the suspension test showed inverted U sign. Deep tendon reflexes were weakly preserved. She was fully examined for muscular disease at the age of 6 months, at which time she could not yet control her head. However the Bayley Scales of Infant Development for language and cognitive development were normal. Her serum creatine kinase (CK) level was elevated to 2,184 IU/L (0-50 norm) and her serum aldolase level was also high at 31.6 sigma U/mL (0-7.6 norm). In a nerve conduction study, both sensory and motor conduction were shown to be normal. Electrocardiography and echocardiography showed no abnormalities. Brain magnetic resonance imaging (MRI) performed at the age of 6 months showed excessive T2 hyper-intensity at the peritrigone and external capsule (
Typical clinical features of MDC1A or merosin deficient congenital muscular dystrophy include severe floppiness at birth, elevated serum CK, delayed motor milestones, white matter changes as seen on brain MRI, and normal intelligence
In our case, the onset of symptoms was 4 months after birth, rather than during the neonatal period. Usually, merosin deficient patients present with symptoms within 7 days of birth, while patients with residual merosin have a later onset of symptoms. The other symptoms of this patient, such as hypotonia, normal intelligence, elevated serum CK, and the absence of seizures, are typical presentations of MDC1A patients. At present, she is 14 months old, and can sit without support but cannot get into a sitting position. We estimate that she has about a 50% probability of walking independently later in her life.
Brain MRI of this patient showed typical hyperintensity in the T2-weighted image. However, the patient's site of lesion is in the external capsule, which is an unusual area for this disease. A study of 25 Brazilian patients with MDC1A reported that bilateral white matter involvement in the parietal, frontal, and temporal regions was frequent, and brain stem, cerebellum, and internal and external capsules were also affected in a minority of cases
To confirm mutation of the
MDC1A is very rare in Asia, and the cases reported thus far are typically those without merosin, and have mostly been severe forms of MDC1A. In our study, the patient showed a typical phenotype of MDC1A, including features such as hypotonia, elevated serum CK, delayed motor development, and T2 hyperintensity on brain MRI. However, immunohistochemical staining of the muscle fibers showed partially decreased merosin levels and some atypical findings, such as a somewhat later age of disease onset and involvement of the external capsule. From our experience, performing immunohistochemical staining to assay the extent of merosin expression is an important procedure, and may be helpful in predicting the clinical course of the disease.
This work was supported by a National Research Foundation grant funded by the Korean government (MEST) (2010-0020353).
No potential conflict of interest relevant to this article was reported.
Axial T2-weighted brain magnetic resonance images of the patient at 6 months of age shows high signal intensity in the white matter of the peritrigone and external capsule (A); slight progression of dysmyelination can be seen 2 months later (B).
Hematoxylin and eosin staining shows marked muscle fiber size variation, increased endomysial fibrosis, numerous endomysial inflammatory cell infiltrations, and increased necrotic and regenerative muscle fibers (A, ×200; B, ×400).
Immunohistochemical staining of the patient's muscle fiber demonstrates partially decreased laminin α2 expression (A, ×400) comparing with normal expression of dystrophin (B, ×400) and α-dystroglycan (C, ×400).