Genetic insights into the causes and classification of the cerebral palsies

Abstract

Cerebral palsy (CP), the most common physical disability of childhood, is a clinical diagnosis that encompasses a highly heterogeneous group of neurodevelopmental disorders resulting in movement and posture impairments that persist throughout life. Despite being commonly attributed to a variety of environmental factors, particularly to birth asphyxia, the specific cause remains unknown in the majority of individuals. Conversely, a growing body of evidence suggests that CP is likely caused by multiple genetic factors, similar to other neurodevelopmental disorders, such as autism and intellectual disability. Due to recent advances in next-generation sequencing technologies, it is now possible to sequence the entire human genome in a rapid and cost-effective way. It is likely that novel CP genes will be identified as more researchers and clinicians use this approach to study individuals with undiagnosed neurological disorders. As our knowledge of the underlying pathophysiologic mechanisms increases, so does the possibility of developing genomically-guided therapeutic interventions for CP.

Rare copy number variation in cerebral palsy

“…5 There is evidence of genetic susceptibility to CP but little is known about possible mechanisms. 6 Monozygotic twins have a significantly higher (P ¼ 0.0026) concordance rate for CP compared with dizygotic twins. 7 Several family studies have determined the likely inheritance pattern responsible for different clinical manifestations of CP.…”

Treating an intervention level 1 patient: futile or brave?

“…[4][5][6][7][8][9] It has been documented that CP occurs in 2-2.5/1 000 live births. 10 Causes of CP include being born before term, not receiving enough oxygen during the birth, the foetus being exposed to maternal infection and/or inflammation in utero, and maternal fever during labour.…”

“…10 Causes of CP include being born before term, not receiving enough oxygen during the birth, the foetus being exposed to maternal infection and/or inflammation in utero, and maternal fever during labour. 6 CP is classified according to movement disorder as either spastic, ataxic, dystonic or athetotic, and according to limb involvement as hemiplegic or quadriplegic. 7 CP sufferers often have visual, hearing and cognitive defects and epilepsy.…”

“…7 CP sufferers often have visual, hearing and cognitive defects and epilepsy. [5][6][7]9,11 Other systemic defects are also present, the most common noncerebral defects being cardiac (29%), musculoskeletal (14%), urinary tract (9%) and facial clefts (9%). 2,6 CP sufferers also often experience feeding problems because of poor hand to mouth coordination, spilling, poor lip closure and frequent regurgitation or vomiting which results in malnutrition.…”

“…[5][6][7]9,11 Other systemic defects are also present, the most common noncerebral defects being cardiac (29%), musculoskeletal (14%), urinary tract (9%) and facial clefts (9%). 2,6 CP sufferers also often experience feeding problems because of poor hand to mouth coordination, spilling, poor lip closure and frequent regurgitation or vomiting which results in malnutrition. 12 Being malnourished reduces CP-sufferers' well-being, decreases their quality of life and limits their ability to participate in their rehabilitation therapy and other activities.…”