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 .