Handbook of Genetic Counseling/Cerebral Palsy

Cerebral palsy Contracting What is your understanding of why you were referred to genetics? What questions or concerns would you like us to address today? Set agenda for the session Etiology Heterogeneous group of conditions usually leading to ataxia Sometimes inherited in autosomal dominant, autosomal recessive, or X-linked form in familial cerebellar hypoplasia Inheritance Condition Features Autosomal Dominant Cerebellar Vermis Aplasia Female Sex Bias Autosomal recessive Cerebellar hypoplasia with or without retinal pigment abnormality Presents in infancy Cerebellar granule cell hypoplasia 2 or more types, one with severe microcephaly Cerebellar ataxia with neuronal migration defect Absence of muscle disease Pontoneocerebellar atrophy with extrapyramidal dyskinesia Fatal infantile olivopontocerebellar hypoplasia Neronal loss in olives and pontine nuclei, white matter gliosis, microcephaly Cerebellar atrophy with infantile striatal degeneration Progressive epilepsy, mental handicap, death after febrile illness Gillespie syndrome Cerebellar atrophy, aniridia, mental handicap Cerebellar atrophy and anterior horn cell disease Neuromuscular condition similar to type I SMA Cerebellar hypoplasia with progressive pancytopenia (Hyoyeraal-Hreidarsson) Males with growth retardation, microcephaly, pancytopaenia (X-linked?) Cerebellar atrophy, renal and liver disease Carbohydrate-deficient glycoprotein syndrome X-linked (possibly) Paine syndrome Hypoplasia of pons and olives, microcephaly, epilepsy, mental handicap, spasticity X-linked dominant vermis aplasia Preponderance of female-to-female transmission Cerebellar vermis aplasia, holoprosencephaly syndrome Male sibs affected by holoprosencephaly and/or vermis aplasia Congenital and childhood-onset ataxias tend to be autosomal recessive Adult-onset conditions tend to be autosomal dominant May also be due to teratogenic insults Methymercury Retinoic acid Anticonvulsants Most common cause is hypoxic/ischemic injury in perinatal period or early childhood Anoxia Trauma to the brain at birth Can be caused by cerebral injury later in life Clinical Features Several classes with different features Spastic diplegia Onset several weeks or months after birth Delay in normal development, especially motor skills Results from prenatal or perinatal insult Walking attempted much later and results in characteristic stance and gait Legs advanced stiffly in short steps like arc of circle May have scissors gait with crossing over of legs Lower legs splayed out, feet flexed and turned in, heels not touching ground Posture alternates between extremes of supination and pronation Walking accompanied often by rotary movements of neck and facial grimacing Legs short and small but muscles not atrophic Arms may also be mildly affected Hemiplegia Difference in function of right and left extremities noticed after birth or 6-12 months Accounts for about 1/3 of children with cerebral palsy Affects arms first, noticed in legs when learning to walk Mental defects depend on whether brain lesion confined to one hemisphere Convulsions (35-50%) Seizures may accompany onset if develops during childhood Usually limited to hemiplegic side of body May persist throughout life Double hemiplegia Occurs less frequently than hemiplegia Bilateral weakness of face, arms, and legs Begins at any age due to acquired cerebral disease May be due to bilateral cerebral lesion or high cervical cord lesion May also be produced in infant by fracture-dislocation of cervical spine by breech delivery Arms severely affected Congenital choreoathetosis Recognized after several months or a year Causes some combination of chorea, athetosis, ballismus, myoclonus, and dystonia Causes defect in voluntary movement May be mild resulting in "fidgets" May be severe, intense involuntary movements Even with rehabilitation, the most severe rarely achieve enough motor control to live independent life Intelligence may not be affected Kernicterus Was common when postnatal serum bilirubin was kept below 15 mg/dL Majority of infants die within 1 or 2 years Survivors usually mentally retarded, deaf, and totally unable to sit, stand, or walk Several patients reportedly were not mentally retarded and learned to walk backwards Have rigid limbs Management/Treatment Options Outcome depends on severity of associated intellectual handicaps Early application of stretching to prevent contractures Orthopedic appliances and surgical procedures to improve mobility Special education to help with motor problems and intellectual involvement Prevention is great challenge Prevention of kernicterus by phototherapy has helped Providing low-birth weight infants with extra care may help More prone to respiratory distress Must provide good surveillance of respiratory function Differential Diagnosis Leukodystrophy - spinal tap showing elevated spinal fluid indicates leukodystrophy Hydrocephaly if child has large head Tumor of cerebral hemisphere - disease is progressive Spinal cord lesions - weakness limited to lower extremities Muscular dystrophy - tendon reflexes would be normal Ataxia telangiectasia Recurrence Risks Depends if cause of cerebral palsy can be determined Autosomal recessive Each pregnancy from heterozygote parents has 25% risk of child being affected Each pregnancy has 50% risk of being carrier Autosomal dominant Each child born to affected parent has 50% chance of being affected May also occur due to new mutation so low recurrence risk X-linked Sons of affected males not affected Daughters of affected males must be affected Daughters of carrier females 50% risk of being carriers Sons of carrier females 50% risk of being affected Most cases probably caused by hypoxic or ischemic injury to brain so recurrence risk is low Psychosocial Issues Parental guilt Burden of disease that requires daily management Social stigma Financial pressures, disruption of daily activities for special therapies, orthotics, or other needs Potential need for lifetime care References "Abnormalities of Motor Function (Cerebral Palsy)." Principles of Internal Medicine (1994): 2342. "Cerebellar Hypoplasias." Principles and Practice of Medical Genetics (1997): 2154-2156. "Cerebral Palsy (Little Disease)." Textbook of Pediatrics (1979): 1759-1761. Notes The information in this outline was last updated in 2002.