NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy

McMichael, G.; Haan, Eric; Gardner, Alison; Yap, Tzu Ying; Thompson, Suzanna C.; Ouvrier, Robert; Dale, Russell C.; Gécz, Jozef; MacLennan, Alastair H.

doi:10.1016/j.ejmg.2013.07.003

Cited by 17 publications

(18 citation statements)

References 21 publications

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“…Contemporary genetics studies identify increased de novo copy number variation rates in CP 24 in up to 20%. 25,26 Exome analysis can identify [27][28][29] further genomic abnormalities cohorts of CP. While some genes are novel, studies often ascribe a new role to a previously recognised gene.…”

Section: Genetics Testingmentioning

confidence: 99%

Diagnosing cerebral palsy in full‐term infants

Morgan

Fahey

Roy

et al. 2018

J Paediatrics Child Health

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More than 50% of infants with cerebral palsy (CP) are born at or near term, with the vast majority having pre‐ or perinatally acquired CP. While some have a clinical history predictive of CP, such as neonatal encephalopathy or neonatal stroke, others have no readily identifiable risk factors. Paediatricians are often required to discriminate generalised motor delay from a variety of other diagnoses, including CP. This paper outlines known causal pathways to CP in term‐born infants with a focus on differential diagnosis. Early and accurate diagnosis is important as it allows prompt access to early intervention during the critical periods of brain development. A combination of clinical history taking, standard clinical examination, neuroimaging and genetic testing should be started at the time of referral. Attention to the investigation of common comorbidities of CP, including feeding and sleep difficulties, and referral to early intervention are recommended.

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Section: Genetics Testingmentioning

confidence: 99%

Diagnosing cerebral palsy in full‐term infants

Morgan

Fahey

Roy

et al. 2018

J Paediatrics Child Health

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“…This was nicely demonstrated in a family initially diagnosed with a cerebral palsy like movement disorder, where three members with "hereditary benign chorea" have been identified to carry a 7 bp deletion in exon 1 of the NKX2-1 gene. The mutation is predicted to lead to a frame shift in protein translation and subsequent premature termination of NKX2-1 mRNA translation and NKX2-1 functional haploinsifficiency53 .…”

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confidence: 99%

Cerebral palsy: causes, pathways, and the role of genetic variants

MacLennan

Thompson

Gécz

2015

American Journal of Obstetrics and Gynecology

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359

288

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Cerebral palsy (CP) is heterogeneous with different clinical types, comorbidities, brain imaging patterns, causes, and now also heterogeneous underlying genetic variants. Few are solely due to severe hypoxia or ischemia at birth. This common myth has held back research in causation. The cost of litigation has devastating effects on maternity services with unnecessarily high cesarean delivery rates and subsequent maternal morbidity and mortality. CP rates have remained the same for 50 years despite a 6-fold increase in cesarean birth. Epidemiological studies have shown that the origins of most CP are prior to labor. Increased risk is associated with preterm delivery, congenital malformations, intrauterine infection, fetal growth restriction, multiple pregnancy, and placental abnormalities. Hypoxia at birth may be primary or secondary to preexisting pathology and international criteria help to separate the few cases of CP due to acute intrapartum hypoxia. Until recently, 1-2% of CP (mostly familial) had been linked to causative mutations. Recent genetic studies of sporadic CP cases using new-generation exome sequencing show that 14% of cases have likely causative single-gene mutations and up to 31% have clinically relevant copy number variations. The genetic variants are heterogeneous and require function investigations to prove causation. Whole genome sequencing, fine scale copy number variant investigations, and gene expression studies may extend the percentage of cases with a genetic pathway. Clinical risk factors could act as triggers for CP where there is genetic susceptibility. These new findings should refocus research about the causes of these complex and varied neurodevelopmental disorders.

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“…Metabolic deficiencies, such as sepiapterin reductase deficiency, can also be initially mistaken as CP . Other mutations, such as NKX2‐1 mutation, a slowly progressive chorea, can mimic dyskinetic CP . Although some developmental motor disorders are caused by genetic disorders, there are also genetically recognized causes of CP …”

mentioning

confidence: 99%

“…8 Other mutations, such as NKX2-1 mutation, a slowly progressive chorea, can mimic dyskinetic CP. 9 Although some developmental motor disorders are caused by genetic disorders, there are also genetically recognized causes of CP. 10 Cases of children losing their CP diagnosis have been documented since the beginning of the 20th century.…”

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confidence: 99%

Losing a diagnosis of cerebral palsy: a comparison of variables at 2 and 5 years

Chen

Holzinger

Oskoui

et al. 2019

Develop Med Child Neuro

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AIM This study aims to identify characteristics at 2 years of age that differ between children with confirmed cerebral palsy (CP) and a non-CP diagnosis by 5 years of age.METHOD This was a retrospective cohort analysis. A CP diagnosis may be considered a 'probable' diagnosis at 2 years, which is often 'confirmed' at 4 or 5 years, particularly in the context of CP registries. A total of 1683 children with a diagnosis of CP or probable CP at 2 years of age were identified from the Canadian Cerebral Palsy Registry, of whom 48 received a non-CP diagnosis at 5 years ('non-confirmed CP'). Perinatal adversity, preterm birth status, Gross Motor Function Classification System (GMFCS) level, presence of comorbidities, magnetic resonance imaging (MRI) findings, and initial CP motor type were compared between the two groups by univariate and logistic regression analyses.RESULTS v 2 analysis and multivariate analysis both confirmed that children with a non-CP diagnosis by 5 years of age were more likely to have a normal MRI (v 2 odds ratio [OR]=7.8, 95% confidence interval [CI]=3.8-16.1; OR=5.4, 95% CI=2.4-12.5), ataxic-hypotonic (v 2 OR=10.1, 95% CI=4.9-21.2; OR=6.1, 95% CI=2.2-16.2) or dyskinetic CP (v 2 OR=2.7, 95% CI=1.2-5.9; OR=2.9, 95% CI=1.0-7.6), born at term (v 2 OR=3.7, 95% CI=1.7-8.0; OR=3.6, 95% CI=1.0-12.1), and lack perinatal adversity (v 2 OR=4.1, 95% CI=1.6-10.7; OR=3.4, 95% CI=1.0-11.7).INTERPRETATION Normal MRI, ataxic-hypotonic or dyskinetic CP, lack of perinatal adversity, and term birth are associated with a higher odds of non-CP diagnosis by 5 years of age, thus potentially enhancing diagnostic work-up.

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NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy

Cited by 17 publications

References 21 publications

Diagnosing cerebral palsy in full‐term infants

Diagnosing cerebral palsy in full‐term infants

Cerebral palsy: causes, pathways, and the role of genetic variants

Losing a diagnosis of cerebral palsy: a comparison of variables at 2 and 5 years

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