The genetic basis of cerebral palsy

Fahey, Michael; MacLennan, Alastair H.; Kretzschmar, Doris; Gécz, Jozef; Kruer, Michael C.

doi:10.1111/dmcn.13363

Cited by 162 publications

(157 citation statements)

References 64 publications

(138 reference statements)

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“…These may represent genetic syndromes, consistent with family studies supporting the heritability of CP (5, 6). While genetic association studies have failed to consistently implicate CP-specific loci (7), additional analyses identified potentially pathogenic rare exonic or copy number variants in 10–30% of patients (1, 8). Overall, the available data suggest that the etiology of CP is complex and heterogeneous.…”

Section: Introductionmentioning

confidence: 99%

Cryptorchidism in Boys With Cerebral Palsy Is Associated With the Severity of Disease and With Co-Occurrence of Other Congenital Anomalies

et al. 2018

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BackgroundCryptorchidism is reported in 40–50% of small case series of cerebral palsy (CP) and attributed to hypothalamic–pituitary–gonadal axis abnormalities, intellectual disability (ID), or cremaster spasticity. We collected demographic and clinical data to define the frequency of cryptorchidism and clinical comorbidities in a large CP population.MethodsElectronic health record data were collected for all male patients ≥7 years of age seen in a large, multidisciplinary CP clinic between 2000 and 2016. Variables including age, testicular position, surgical findings, CP severity, birth history, and comorbidities were tested for association using univariable and stepwise backward logistic regression analyses.ResultsOf 839 established patients, testis position was scrotal in 553, undescended in 185 (24%), retractile in 38 (5%), and undocumented in 63 cases. Cryptorchidism were diagnosed at a mean age of 5.8 years, with 20% documented as acquired, and testes were most commonly in the superficial inguinal pouch (41%) and associated with an inguinal hernia (56%). Severity was bilateral in 114/166 (69%) undescended and 24/36 (66%) retractile cases, respectively. Mean birth weight and the frequency of prematurity (55, 58, and 54%) and multiple birth (14, 13, and 9%) were not significantly different among the three groups. We observed a strong ordinal trend in the frequency of comorbidities, including quadriplegia, syndromic features/known genetic disease, intrauterine growth restriction (IUGR), death, brain malformations, seizures, gastrostomy, absent continence, ID and hearing, speech or visual impairment, with the retractile group holding the intermediate position for the majority. The stepwise multivariable analysis showed independent positive associations of cryptorchidism with quadriplegia, syndromic features/known genetic disease, hearing loss, and absent continence, and inverse associations with gestational age and multiple birth.ConclusionThese data suggest that cryptorchidism is less common than previously reported in CP cases, but most strongly associated with quadriplegia. Delayed diagnosis may be related to an acquired condition or to the multiple additional functional deficits that occur in this population. Our data suggest that UDT and CP may both be components of malformation syndromes occurring in singleton births whose clinical features are more likely to include earlier delivery, IUGR, hearing loss, and/or global spasticity.

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Section: Introductionmentioning

confidence: 99%

Cryptorchidism in Boys With Cerebral Palsy Is Associated With the Severity of Disease and With Co-Occurrence of Other Congenital Anomalies

et al. 2018

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“…Hereditary diseases, mainly chromosomal abnormalities, are prevalent in premature infants (3). Beneath neonatal asphyxia, there may be neuromuscular diseases such as Prader-Willi syndrome, congenital myotonic dystrophy, and many clinical conditions leading to hypotonia (1).…”

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confidence: 99%

“…New diseases and syndromes are being defined by chromosomal microarray (MA) and next-generation sequencing (NGS) techniques. Genetic mechanisms discussed in the pathogenesis of CP are mitochondrial inheritance, copy number variation, epigenetic adaptation, and genomic variation/ mutations (3).…”

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confidence: 99%

“…Therefore, the candidate gene or variant has not yet been identified (3). Secondly, it has been shown that MA can enlight account for 10-20% of CPs (3,4). Chromosomal MA is a new, high-resolution chromosome analysis technique.…”

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confidence: 99%

“…Genes responsible for spastic quadriplegic CP classified under hereditary CP are KANK1, AP4E1, AP4M1, AP4B1, and AP4S1 (3,5). Mutations responsible for ataxic CP are found in the genes KCNC3, ITPR1, and SPTBN2 (3).…”

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confidence: 99%

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Cerebral Palsy and Genetics

Akçakaya¹,

Yapıcı²,

Özbek³

2018

tnd

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Development of a Bedside Tool to Predict the Diagnosis of Cerebral Palsy in Term-Born Neonates

et al. 2023

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ImportanceCerebral palsy (CP) is the most common abnormality of motor development and causes lifelong impairment. Early diagnosis and therapy can improve outcomes, but early identification of infants at risk remains challenging.ObjectiveTo develop a CP prognostic tool that can be applied to all term neonates to identify those at increased risk of developing CP.Design, Setting, and ParticipantsThis case-control study used data from the Canadian Cerebral Palsy Registry (data collected from January 2003 to December 2019) for children with CP and the Alberta Pregnancy Outcomes and Nutrition study (mothers enrolled from May 2009 to September 2012; data extracted in 2020) for controls. There were 2771 children with CP and 2131 controls evaluated; 941 and 144, respectively, were removed for gestational age less than 37 weeks at birth, 565 with CP removed for incomplete data, and 2 controls removed for a diagnosis of CP. Data were analyzed from April to August 2022.ExposuresPotential risk factors were selected a priori based on the literature, including maternal, intrapartum, and infant characteristics.Main Outcomes and MeasuresDiagnosis of CP, defined as a disorder of motor function due to a nonprogressive brain abnormality before age 1 year and classified by Gross Motor Function Classification System levels I to V.ResultsOf 3250 included individuals, 1752 (53.9%) were male, and the median (IQR) gestational age at birth was 39 (38-40) weeks. Encephalopathy was present in 335 of 1184 infants with CP (28%) and 0 controls. The final prediction model included 12 variables and correctly classified 75% of infants, with a sensitivity of 56% (95% CI, 52-60) and specificity of 82% (95% CI, 81-84). The C statistic was 0.74 (95% CI, 71-76). Risk factors were found to be additive. A proposed threshold for screening is probability greater than 0.3, with a sensitivity of 65% (95% CI, 61-68) and specificity of 71% (95% CI, 69-73). The prognostic tool identified 2.4-fold more children with CP than would have presented with encephalopathy (odds ratio, 13.8; 95% CI, 8.87-22.65; P &lt; .001).Conclusions and RelevanceIn this case-control study, a prognostic model using 12 clinical variables improved the prediction of CP compared with clinical presentation with encephalopathy. This tool can be applied to all term newborns to help select infants for closer surveillance or further diagnostic tests, which could improve outcomes through early intervention.

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The genetic basis of cerebral palsy

Cited by 162 publications

References 64 publications

Cryptorchidism in Boys With Cerebral Palsy Is Associated With the Severity of Disease and With Co-Occurrence of Other Congenital Anomalies

Cryptorchidism in Boys With Cerebral Palsy Is Associated With the Severity of Disease and With Co-Occurrence of Other Congenital Anomalies

Cerebral Palsy and Genetics

Development of a Bedside Tool to Predict the Diagnosis of Cerebral Palsy in Term-Born Neonates

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