mdc1a is caused by mutation of the laminin -2 gene ( lama2 ) , localized to chromosome 6q22 - 23 .
patients with mdc1a present with severe neonatal hypoxia often requiring ventilatory assistance , markedly delayed motor development , and generalized muscle atrophy with the weakness of limb and trunk muscles leading to contractures and joint deformities .
in contrast with other cmd patients , those with merosin deficiency have high creatine phosphokinase ( cpk ) levels and white matter abnormalities on brain imaging techniques . here
we report the clinical manifestations , result of muscle biopsy and genetic studies in five turkish patients with mdc1a .
the patient 1 was a 6-year - old boy and first attended our hospital at the age of 4 years due to hypotonia , weakness , poor weight gain , and contracture of knees . from birth , he exhibited marked hypotonia with generalized muscle weakness . by 3 years of age , the patient was able to hold his head up but was unable to sit alone . at the age of 5 years , the patient was able to sit unsupported , but not stand .
he had joint contractures of upper and lower extremities , myopathic facies , and pectus carinatum .
nerve conduction studies were normal , and electromyography ( emg ) showed a myopathic pattern . magnetic resonance imaging ( mri ) of the brain was performed and showed high signal in the periventricular and subcortical white matter [ figure 1a and b ] .
periventricular and subcortical white matter signal the patient 2 was the daughter of patient 1 .
she had global hypotonia and was able to sit and was not able to stand .
the distal tone of the four extremities was decreased , and deep tendon reflexes were diminished .
cerebral mri was performed in another hospital and revealed high signal in the periventricular and subcortical white matter .
we analyzed the lama2 gene sequencing and revealed a homozygous mutation c. 639delg in the patient 1 and 2 .
the patient 3 was a 7-month - old girl who presented to our hospital with complaints of developmental motor delays .
her serum cpk level was 4073 u / l , and her echocardiogram was normal .
mri of the brain revealed hyperintense lesions in the periventricular white matter on t2a sequencing .
we studied the lama2 gene sequencing and revealed a homozygous mutation p.r1350 ( c. 4048 c > t ) .
the patient 4 was a 3 and a half year - old boy who presented with hypotonia , weakness , poor weight gain , and respiratory problem , and could not sit or stand .
he had general hypotonia , myopathic facies , pectus excavatum , and he was not able to sit and stand .
furthermore , he had a hemangioma on the left temple , chest , and wrist .
his serum cpk level was 2120 u / l and mri of the brain showed similar findings with other patients .
hemangioma on the left temple , chest , and wrist in the patient 4 the patient 5 was a 6-month - old boy who had hypotonia .
his biochemical investigations were normal except for elevated serum cpk levels ( 2950 u / l ) .
echocardiography was normal , and mri of the brain showed hyperintense lesions in the periventricular white matter .
we performed the lama2 gene sequencing and revealed a homozygous mutation p.r2578 ( c. 7732 c > t ) in two of them .
the patient 1 was a 6-year - old boy and first attended our hospital at the age of 4 years due to hypotonia , weakness , poor weight gain , and contracture of knees . from birth , he exhibited marked hypotonia with generalized muscle weakness . by 3 years of age , the patient was able to hold his head up but was unable to sit alone . at the age of 5 years , the patient was able to sit unsupported , but not stand .
he had joint contractures of upper and lower extremities , myopathic facies , and pectus carinatum .
nerve conduction studies were normal , and electromyography ( emg ) showed a myopathic pattern . magnetic resonance imaging ( mri ) of the brain was performed and showed high signal in the periventricular and subcortical white matter [ figure 1a and b ] .
periventricular and subcortical white matter signal the patient 2 was the daughter of patient 1 .
she had global hypotonia and was able to sit and was not able to stand .
the distal tone of the four extremities was decreased , and deep tendon reflexes were diminished .
cerebral mri was performed in another hospital and revealed high signal in the periventricular and subcortical white matter .
we analyzed the lama2 gene sequencing and revealed a homozygous mutation c. 639delg in the patient 1 and 2 .
the patient 3 was a 7-month - old girl who presented to our hospital with complaints of developmental motor delays .
her serum cpk level was 4073 u / l , and her echocardiogram was normal .
mri of the brain revealed hyperintense lesions in the periventricular white matter on t2a sequencing .
we studied the lama2 gene sequencing and revealed a homozygous mutation p.r1350 ( c. 4048 c > t ) .
the patient 4 was a 3 and a half year - old boy who presented with hypotonia , weakness , poor weight gain , and respiratory problem , and could not sit or stand .
he had general hypotonia , myopathic facies , pectus excavatum , and he was not able to sit and stand .
furthermore , he had a hemangioma on the left temple , chest , and wrist .
his serum cpk level was 2120 u / l and mri of the brain showed similar findings with other patients .
hemangioma on the left temple , chest , and wrist in the patient 4 the patient 5 was a 6-month - old boy who had hypotonia .
his biochemical investigations were normal except for elevated serum cpk levels ( 2950 u / l ) .
echocardiography was normal , and mri of the brain showed hyperintense lesions in the periventricular white matter .
we performed the lama2 gene sequencing and revealed a homozygous mutation p.r2578 ( c. 7732 c > t ) in two of them .
mdc1a is an autosomal recessive neuromuscular disorder caused by mutations in the lama2 gene encoding the laminin - a2 chain a component of the skeletal muscle extracellular matrix protein laminin-211 .
laminin-211 , the most abundant laminin in muscle , is also expressed in schwann cells , the synaptic basal lamina of peripheral nerves , heart , epidermis and fetal trophoblastic tissue .
typical clinical features of mdc1a or merosin - deficient cmd include severe floppiness at birth , elevated serum cpk , delayed motor milestones , white matter changes as seen on brain mri . in literature ,
several studies have reported respiratory insufficiency , feeding difficulties , cardiomyopathy , sensory and motor demyelinating neuropathy , seizure , and external ophthalmoplegia .
severe proximal weakness was also present from birth or developed within the first 6 months .
di blasi et al . reported 9 patients with mdc1a from 1 sudanese and 3 saudi families .
another study presented similar results : five of 13 patients with residual merosin and two of 33 patients with absent merosin could walk independently .
leite et al . in a study of 25 brazilian patients with mdc1a reported that bilateral white matter involvement was frequent in the parietal , frontal , and temporal regions , brain stem , cerebellum , and internal and external capsules were also affected in the minority of cases .
however , they described that there were no correlations with sites of white matter abnormalities and clinical or merosin status . in another study , di blasi et al . reported mri or ct ,
oliveira et al . performed in 22/26 patients , revealed white matter changes in all cases .
in addition , they detected that other cerebral changes included abnormal gyration in three patients . in our study , all the patient showed the typical phenotype of mdc1a , including features such as hypotonia , elevated serum creatine kinase , delayed motor development , and t2 hyperintensity on brain mri . in the patient 3 , 4 , and 5 , we detected two lama2 gene mutations which have been described previously .
coral - vazquez et al . reported an 8-month - old mexican female infant , from a consanguineous family , with mdc1a and they detected homozygous mutation p.r2578 in lama2 gene as similarly in our patient 4 and 5 .
from the 1 month of life , the patient was hypotonic with poor intake , irritability , reduced spontaneous movements , and poor suction .
physical examination showed generalized muscle weakness and contractures of elbows , wrists , knees , and ankles .
patients should be suspected as mdc1a if they have early - onset severe hypotonia with joint contractures , motor developmental delay with moderately increased cpk levels , and abnormal cerebral imaging findings .
muscle biopsy and molecular genetic testing should be performed for diagnosis and especially for the genetic counseling .
 context : congenital muscular dystrophy type 1a ( mdc1a ) is caused by mutations in the laminin -2 gene encoding laminin-a2.aims:the purpose of this study is to determine clinical and genetic results in five turkish patients with mdc1a.setting and designs : five children with mdc1a were retrospectively analyzed.results:three ( 60% ) were boys , and 2 ( 40% ) were girls . 
 parental consanguinity was found in all the families . in all the patients , hypotonia , weakness , delayed motor milestones , 
 markedly elevated creatine phosphokinase ( cpk ) concentration , and brain white matter abnormalities on magnetic resonance imaging were detected . 
 mutation analysis was performed in all the patients , and 3 different mutations were detected . 
 however , a mutation in patient 1 and 2 has not been previously described in the literature.conclusions:when a patient presents with severe congenital hypotonia , muscle weakness , high serum cpk levels , and white matter abnormalities , should be suspected as mdc1a . 
Introduction
Materials and Methods
Patients
Discussion
Conclusions
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