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A 19-year-old Australian Indigenous woman presented after suffering a ventricular fibrillation cardiac arrest whilst swimming, leading to near drowning, in a remote Aboriginal community of South Au...

To estimate epidemiologic risk factors for cerebral palsy.Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non-cerebral palsy controls.The following factors were associated with cerebral palsy: recorded maternal infection during pregnancy (41.4% patients compared with 31.3% controls; odds ratio [OR] 1.55, 95% confidence interval 1.26-1.91), small for gestational age ([birth weight less than third customized centile] 43.9% patients compared with 6.3% controls; OR 11.75, 6.25-22.08), gestational age less than 32 weeks (29.3% patients compared with 0.7% controls; OR 59.20, 28.87-121.38), multiple birth (OR 6.62, 4.00-10.95), a relative with cerebral palsy (OR 1.61, 1.12-2.32), breech position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76-3.49), bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls; OR 2.04, 1.61-2.58), male sex (58.8% patients compared with 45.8% controls; OR 1.68, 1.38-2.06), multiple miscarriage (7.7% patients compared with 3.5% controls; OR 2.30, 1.38-3.82), smoking (14.0% patients compared with 10.6% controls; OR 1.37, 1.02-1.85), and illicit drug use (3.3% patients compared with 1.5% controls; OR 2.22, 1.14-4.30). Factors not associated with cerebral palsy were "disappearing twin," diabetes, maternal body mass index, hypertension, alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery, and maternal age.Preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth present the largest risks for a cerebral palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal infections during pregnancy were not associated with cerebral palsy.II.

ObjectiveTo provide new insights into theFOXG1-related clinical and imaging phenotypes and refine the phenotype-genotype correlation inFOXG1syndrome.MethodsWe analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenicFOXG1variant and performed phenotype-genotype correlations.ResultsA total of 37FOXG1different heterozygous mutations were identified, of which 18 are novel. We described a broad spectrum of neurodevelopmental phenotypes, characterized by severe postnatal microcephaly and developmental delay accompanied by a hyperkinetic movement disorder, stereotypes and sleep disorders, and epileptic seizures. Our data highlighted 3 patterns of gyration, including frontal pachygyria in younger patients (26.7%), moderate simplified gyration (24.4%) and mildly simplified or normal gyration (48.9%), corpus callosum hypogenesis mostly in its frontal part, combined with moderate-to-severe myelination delay that improved and normalized with age. Frameshift and nonsense mutations in the N-terminus ofFOXG1, which are the most common mutation types, show the most severe clinical features and MRI anomalies. However, patients with recurrent frameshift mutations c.460dupG and c.256dupC had variable clinical and imaging presentations.ConclusionsThese findings have implications for genetic counseling, providing evidence that N-terminal mutations and large deletions lead to more severeFOXG1syndrome, although genotype-phenotype correlations are not necessarily straightforward in recurrent mutations. Together, these analyses support the view thatFOXG1syndrome is a specific disorder characterized by frontal pachygyria and delayed myelination in its most severe form and hypogenetic corpus callosum in its milder form.

To describe and characterize the prevalence and quality of pain in a population-based community sample of children with hemiplegic cerebral palsy.Outcomes were assessed from 2 domains of the World Health Organization International Classification of Functioning, Disability and Health: body structure/function (upper limb spans, modified Ashworth scale, Tardieu scale, sensory function), activities-participation (Assessment of Motor and Process Skills), Pediatric Quality of Life Inventory (PedsQL), and self-perception (Harter Self-Perception Profile).There were 107 participants of age (mean, 95% confidence interval) 8.94 years (8.23 to 9.65); 61 (57%) were boys and 58 (54%) had hemiplegia affecting the right side. Fifty-one (48%) reported pain. Pain mostly affected the involved side (n=28, 55%) and lower limb (n=19, 37%). Eighteen (35%) reported moderate to severe pain. Thirty-five (69%) said pain impacted on movement/activity and was of an aching quality (n=29, 57%). Mean (95% confidence interval) quality of life according to Pediatric Quality of Life Inventory was significantly lower for children experiencing pain compared with children experiencing no pain [parent 50.2 (45.9 to 54.5) vs. 60.1 (55.1 to 65.1), P0.01; child 60.5 (55.4 to 65.6) vs. 75.8 (68.4 to 83.2), P0.01]. The self-perception domains of Scholastic Competence [no pain, 3.02 (2.78 to 3.26); pain, 2.55 (2.31 to 2.79) P0.01] and Behavioral Competence [no pain, 3.33 (3.07 to 3.60); pain, 2.88 (2.70 to 3.06) P0.01] were significantly lower in children with pain agedor =8 years.Pain is common in children with hemiplegic cerebral palsy with qualities suggesting a nociceptive origin. Pain is associated with lower quality of life and self-perception. Results suggest clinicians should assess and actively manage pain in this population.

Two unrelated girls with craniosynostosis and bilateral cleft lip and palate who also had developmental delay and umbilical herniae are presented. We propose that these patients have the same condition, and that their combination of features may constitute a new syndrome. Management of the patients is discussed.

Herpes viruses are able to cross the placenta and infect the fetus. Being potentially neurotrophic, they might contribute-directly or indirectly-to cerebral palsy. This population-based case-control study examined the association between perinatal exposure to neurotrophic viruses and cerebral palsy in 414 white South Australian case patients having the disorder and 856 controls. Newborn infants were screened for viral nucleic acids of enteroviruses and herpes viruses using the polymerase chain reaction technique. The herpes group A viruses sought included herpes simplex virus (HSV)-1, HSV-2, Epstein-Barr virus, cytomegalovirus, and human herpes virus 8. The herpes group B viruses included varicella zoster virus and human herpes viruses 6 and 7. A significant association was found, at all gestational ages, between any type of viral exposure and the development of cerebral palsy. Herpes group B viruses increased the risk of all types of cerebral palsy (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.09-2.59). A similar risk was noted for the diplegic and hemiplegic subtypes of cerebral palsy. Associations with any of the other viruses tested for were not statistically significant. With a gestational age of 37 weeks or more, the risk of cerebral palsy increased if any herpes virus was detected (OR, 1.52; 95% CI, 1.09-2.13) and also with the detection of any virus (OR, 1.64; 95% CI, 1.17-2.28). With a gestational age less than 37 weeks, detection of a herpes group A virus decreased the risk of all types of cerebral palsy (OR, 0.65; 95% CI, 0.43-0.99). Detecting a herpes group B virus increased the risk of quadriplegia (OR, 2.87; 95% CI, 1.09-7.59). At no gestational age was the presence of more than one virus associated with the risk of cerebral palsy. Newborn infants in South Australia are commonly exposed to neurotrophic viruses, and this is especially the case for preterm infants. Exposure to a herpes group B virus nearly doubles the risk of cerebral palsy. It remans possible that other factors such as genetic susceptibility to infection, growth restriction, and prematurity are necessary for brain damage and cerebral palsy to occur.

The incidence of cerebral palsy (CP) has not decreased over the past 4 decades. A number of small studies have suggested a possible association between CP and thrombophilia. Both inherited and acquired thrombophilias affecting the mother and/or the fetus may lead to thrombosis and adverse pregnancy outcomes, including CP. This population-based case-control study sampled genome DNA from 443 newborn infants with CP and 883 control infants. The study population included all children with CP born in South Australia in the years 1986-1999. Participants were screened for 4 common polymorphisms associated with thrombophilia: factor V Leiden (FVL, G1691A), prothrombin gene mutation (PGM, G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C. Compound heterozygosity for MTHFR C677T and MTHFR A1298C was also evaluated. First, infants of all gestational ages at birth were grouped together for analysis. There was an association between homozygous or heterozygous MTHFR C677T and diplegia (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.09-2.46), but no other statistically significant positive association between any of the thrombophilias and CP. For infants with quadriplegia, homozygosity for MTHFR A1298C was negatively associated with CP (OR, 0.33; 95% CI, 0.1-0.87). When only children born at 37 weeks gestation or later were analyzed, no significant relationship was evident between thrombophilias and CP. However, when only infants born preterm were evaluated, several strong associations were found. In infants born at 32 to 26 weeks gestation, the MTHFR C677T polymorphism was associated with all types of CP combined: the OR for heterozygotes was 1.91 (95% CI, 1.01-3.66), and for homozygotes, it was 2.55 (95% CI, 1.12-5.74). The MTHFR A1298C mutation was negatively associated with diplegia in the same infants (OR, 0.16; 95% CI, 0.02-0.70). In 405 infants with CP born at a gestational age less than 32 weeks, homozygosity for MTHFR C677T correlated with diplegic CP (OR, 2.76; 95% CI, 1.21-6.12), and homozygosity for FVL correlated with quadriplegic CP (OR, 9.12; 95% CI, 0.86-57.71). Homozygosity for FVL increased the risk of diplegic CP 26 times more than heterozygosity (OR, 26; 95% CI, 1.09-1551.59). Compound thrombophilias were also considered. The combination of heterozygosity for PGM and homozygosity for MTHFR C677T was associated with quadriplegia at all gestational ages (OR, 5.33; 95% CI, 1.06-23.25).

Although the clinical delineation of the majority of overgrowth syndromes is straightforward, we believe there is a subset of patients with overlapping features from a number of overgrowth syndromes. We report a patient with hemimegalencephaly, hemihypertrophy, macrocephaly, vascular lesions, psychomotor retardation and intestinal lymphangiectasia. The clinical history and findings posed a diagnostic dilemma as the features overlapped between several conditions, namely macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC), Klippel-Trenaunay-Weber syndrome (KTWS), Proteus syndrome and a provisional unique syndrome described by Reardon et al. (1996, Am J Med Genet 66:144-149). We anticipate that only when the molecular basis is delineated will it become clear whether these disorders are separate entities or merely differing ends of the same spectrum.

We describe a 14-year-old male with dissection of the descending aorta, bilateral iris hypoplasia, striae distensae and brachytelephalangy, the latter being most marked in the thumbs. Inguinal herniae and a patent ductus arteriosus were surgically repaired in infancy. The pattern of abnormalities may constitute a previously undescribed syndrome. The proband died suddenly at the age of 17 years.

A 9-year-old girl with craniosynostosis, facial dysmorphism, mental retardation, proportionate short stature and acral abnormalities is described, in whom both clinical and radiological features support a diagnosis of Hunter-McAlpine syndrome. Her mother is mildly affected, confirming previous evidence that this syndrome is dominantly inherited and shows considerable phenotypic variability within families.