congenital muscular dystrophy type 1a ( mdc1a ) was first described in 1994 as a variant form of classic congenital muscular dystrophy ( cmd)1 ) .
mdc1a is an autosomal recessive disorder , and patients show absent merosin ( laminin 2 ) on skeletal muscle biopsy . a mutation in the laminin 2 ( lama2 ) gene , located on 6q22 - 23 ,
most patients with mdc1a show absent merosin in muscle immunohistochemistry studies , however , there have been some reports of cases of mdc1a with residual merosin expression3,4,5 ) .
mdc1a is very rare in asian countries . comparing with studies conducted in western countries2,3 ) ,
only a few cases without merosin expression have been reported in the asian population6,7,8 ) . here
the patient was born at 38 weeks of gestation with a birth weight of 3,500 gm .
she was a second child , with one 4-year - old brother with no medical problems .
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 .
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 ,
brain magnetic resonance imaging ( mri ) performed at the age of 6 months showed excessive t2 hyper - intensity at the peritrigone and external capsule ( fig .
1 ) . repeated brain mri at the age of 8 months showed progression of dysmyelination .
hematoxylin and eosin staining showed marked muscle fiber size variation , increased endomysial fibrosis , many endomysial inflammatory cell infiltrations , and many necrotic and regenerative muscle fibers ( fig .
modified gomori trichrome staining did not show ragged red fibers , nemaline bodies , or rimmed vacuoles .
immunohistochemical staining was performed using antibodies against the c - terminal of dystrophin , rod domain of dystrophin , n - terminal of dystrophin , -sarcoglycan , -sarcoglycan , -sarcoglycan , -sarcoglycan , dysferlin , -dystroglycan , caveolin 3 , and laminin 2 . staining against laminin 2
3 ) . to confirm mutation in the lama2 gene , we performed direct sequencing of exons 14 , 25 , 26 , and 27 , all of which are known as common sites of mutation .
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 intelligence2 ) .
however , merosin - positive cmd generally presents with less severe clinical features and without any abnormalities on brain mri2,5 ) .
initially , mdc1a was thought to be a homogenous disease ; however , case reports of atypical phenotypes and some cases showing only partially reduced merosin expression contributed to classifying the disease as a heterogeneous group3,5 ) .
there have been mdc1a patients who show late - onset weakness , mental retardation , seizures , subclinical cardiac involvement , or neuronal migration defects9 ) . in particular , cases with residual merosin expression
have more variable phenotypes than cases with absolute merosin deficiency . according to previous reports , patients with residual merosin tend to have milder phenotypes3,5 ) . with regards to ambulation
, a previous study showed that eight out of 12 patients with residual merosin achieved independent ambulation , whereas , out of four patients with absent merosin , none could walk independently5 ) .
another study presented similar results : five out of 13 patients with residual merosin and two out of 33 patients with absent merosin could walk independently3 ) . 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 can not get into a sitting position .
we estimate that she has about a 50% probability of walking independently later in her life .
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 cases10 ) .
however , there were no correlations with sites of white matter abnormalities and clinical status or merosin status . to confirm mutation of the lama2 gene , we sequenced exons 14 , 25 , 26 , and 27 .
this technique , while able to screen for point mutations in above 4 exons , is limited in its ability to detect large deletions or insertions or point mutations in the other sites .
we did not further evaluate other possible mutations in the lama2 gene because of her parents ' refusal . according to a previous report
, a majority of mutations in the residual merosin group are splice site mutations , and frameshift mutations are less frequent3 ) .
this patient may have mutations in her lama2 gene , although we could not confirm the specific mutations because of incomplete study .
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 .
 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 2 ( lama2 ) gene , located at 6q22 - 23 , is a genetic cause of mdc1a . 
 patients have merosin ( laminin 2)-deficient skeletal muscles . however , the degree of merosin expression ranges from total absence to partial reduction . 
 patients with residual merosin expression have more variable and milder phenotypes than those with absolute merosin deficiency . 
 we observed a korean girl with mdc1a with residual merosin expression . 
 clinical presentation of this patient was typical except for late onset of the disease and external capsule involvement . 
 immunohistochemical staining of muscle fibers including merosin , is important to evaluate patients with hypotonia , delayed motor development , and abnormal white matter changes . 
Introduction
Case report
Discussion