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FCMD is caused by mutations in the fukutin gene, which is located on chromosome 9q31167 170 Fukutin is a secretory enzyme that localizes to the cis-Golgi compartment and is thought to be involved in that has a role in posttranslational glycoslylation of -dystroglycan137 In addition to the skeletal muscle involvement, the disruption of normal glycosylation of -dystroglycan or other proteins leads to defects in neuronal migration and differentiation, which accounts for the many abnormalities seen within the central nervous system

WWS, or cerebro-ocular dysplasia, is the most severe -dystroglycanopathy and is associated with a life expectancy of less than 3 years WWS presents as severe generalized weakness hypotonia in infancy163 165 In addition, the infants are usually born blind secondary to ocular malformations, which include xed pupils, hypoplasia of the optic nerves, micro-ophthalmia, corneal opacities, cataracts, shallow anterior chambers, ciliary body abnormalities, iridolental synechiae, and retinal dysplasia and detachment As with FCMD and MEB, WWS is associated with migrational and developmental disturbances of neurons in the brain, which include lissencephaly, polymicrogyria, hydrocephalus, hypomyelination of the subcortical white matter, and hypoplasia of the brainstem and vermis Seizures are common

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FCMD was originally described in Japan, where it is the most common form of MDC141,142,167 The myopathy presents with generalized proximal greater than distal weakness and hypotonia in infants Mothers of affected children in retrospect often note decreased fetal movements There is an increased frequency of spontaneous abortions of affected fetuses Pseudohypertrophy of the calves is recognized in approximately half the children Muscle stretch re exes are reduced Some children are born with arthrogryposis and contractures are progressive In addition to the myopathy, FCMD is associated with severe structural abnormalities of the brain, including microcephaly, cortical dysplasia, lissencephaly, pachygyria, polymicrogyria, and hydrocephalus167,168 Intellectual function is markedly compromised Approximately 50% of children who are affected have seizure Both physical and mental developments are delayed, with the majority never being able to stand or ambulate independently Most children die by the age of 10 12 years of age from respiratory failure

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Serum CK levels are elevated Brain MRI scans reveal structural abnormalities, which are alluded to in the above section Electroencephalography is often abnormal, revealing slowing of the background and epileptiform activity

The mutations have been identi ed in genes that encode for four proteins (POMT1, POMT2, fukutin, and FKRP) in patients with WWS, but they account for only a minority of cases141,163 165,171 Mutations in the POMT1 gene on chromosome 9q31 33 account for the 20% of WWS141,164 The clinical phenotype of patients with

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OBJECTS section Near the top of that section, below all the other variables you created, create a variable called score, with a data type of Number

mutations in the POMT1 gene is also variable, with rare cases being reported with LGMD and mild mental retardation (LGMD 2K)172 As noted previously, glycosylation of -dystroglycan is required for normal binding to merosin162

CK levels were always very elevated (10 75 normal) Echocardiogram may reveal features of a dilated cardiomyopathy Pulmonary function tests may reveal reduced forced vital capacity and inspiratory pressures MRI of the brain may reveal microcephaly, cerebellar cysts, and hypoplasia of the vermis, and also white matter abnormalities on MRI as other alpha-dystroglycanopathies176

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MEB disease was initially described in Finnish patients by Santavouri and colleagues 164,165,173 175 but has been subsequently reported in other populations As in WWS, brain and eye abnormalities accompany the muscle weakness; however, MEB is less severe Although infants are weak and motor development is slow, most affected children eventually can sit and stand and some ambulate There are severe cognitive impairments associated with structural abnormalities in the brain, which include pachygyria, polymicrogyria, abnormal midline structures, and hypoplasia of the vermis and pons MEB is also associated with progressive myopia, glaucoma, and late cataracts

// --------DECLARE VARIABLES AND CREATE OBJECTS---------------var meteorNum:Number = 0; var meteorInterval:Number; var meteorInit:Object = new Object(); var score:Number;

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