LETHAL CONGENITAL MUSCULAR-DYSTROPHY IN 2 SIBS WITH ARTHROGRYPOSIS MULTIPLEX - NEW ENTITY OR VARIANT OF COBBLESTONE LISSENCEPHALY SYNDROME

We report on two sisters of first degree cousin parents who were born with severe hypotonia, arthrogryposis multiplex congenita (AMC) and dy smorphic features consistent with the fetal akinesia/hypokinesia seque nce. They needed assisted ventilation and each died at the age of 5 mo nths. Both had type II lissencephaly (cobblestone lissencephaly) which was visualized by magnetic resonance imaging (MRI) in the proband. Op hthalmic evaluation revealed no occular malformations in either of the m. Brain auditory evoked potentials (BAEP) revealed bilateral severe s ensorineural hearing loss in the proband, whereas an MRI-guided open m uscle biopsy of the sartorius muscle (the only remaining thigh muscle) showed features of muscular dystrophy. Immunohistochemistry revealed normal dystrophin, dystrophin-associated glycoproteins (DAG) and meros in. Certain clinical and pathological features distinguish the disease seen in these sisters from reported isolated cases where lethal AMC w as associated with brain dysplasia and from the main syndromes of cong enital muscular dystrophy/cobblestone lissencephaly. Differences from the Walker-Warburg syndrome, which simulates it in severity, included the absence of severe hydrocephalus, normal creatine kinase (for age) and minimal (mainly periventricular) white matter abnormalities. The f indings suggest either an independent entity, in the studied family or an allelic variation of the cobblestone Lissencephaly (type II lissen cephaly) syndrome.