FOXP2 is not a major susceptibility gene for autism or specific language impairment

The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment

Effect of salt supplementation of newborn premature infants on neurodevelopmental outcome at 10–13 years of age

Background: The nutritional requirements of prematurely born infants are different from those of babies born at term. Inadequate or inappropriate dietary intake in the neonatal period may have long term adverse consequences on neurodevelopmental function. The late effect of neonatal sodium deficiency or repletion in the premature human infant on neurological development and function has not been examined, despite evidence in animals of a serious adverse effect of salt deprivation on growth of the central nervous system. Methods: Thirty seven of 46 children who had been born prematurely (gestational age of 33 weeks or less) and allocated to diets containing 1–1.5 mmol sodium/day (unsupplemented) or 4–5 mmol sodium/day (supplemented) from the 4th to the 14th postnatal day were recalled at the age of 10–13 years. Detailed studies of neurodevelopmental performance were made, including motor function and assessment of intelligence (IQ), memory and learning, language and executive skills, and behaviour. Sixteen of the children were found to have been in the supplemented group and 21 in the unsupplemented group. Results: Children who had been in the supplemented group performed better in all modalities tested than those from the unsupplemented group. The differences were statistically significant (analysis of variance) for motor function, performance IQ, the general memory index, and behaviour as assessed by the children's parents. The supplemented children outperformed the unsupplemented controls by 10% in all three components of the memory and learning tests (difference not significant but p < 0.1 for each) and in language function (p < 0.05 for object naming) and educational attainment (p < 0.05 for arithmetic age). Conclusions: Infants born at or before 33 weeks gestation require a higher sodium intake in the first two weeks of postnatal life than those born at or near term, and failure to provide such an intake (4–5 mmol/day) may predispose to poor neurodevelopmental outcome in the second decade of life

Effect of salt supplementation of newborn premature infants on neurodevelopmental outcome at 10–13 years of age

Background: The nutritional requirements of prematurely born infants are different from those of babies born at term. Inadequate or inappropriate dietary intake in the neonatal period may have long term adverse consequences on neurodevelopmental function. The late effect of neonatal sodium deficiency or repletion in the premature human infant on neurological development and function has not been examined, despite evidence in animals of a serious adverse effect of salt deprivation on growth of the central nervous system. Methods: Thirty seven of 46 children who had been born prematurely (gestational age of 33 weeks or less) and allocated to diets containing 1–1.5 mmol sodium/day (unsupplemented) or 4–5 mmol sodium/day (supplemented) from the 4th to the 14th postnatal day were recalled at the age of 10–13 years. Detailed studies of neurodevelopmental performance were made, including motor function and assessment of intelligence (IQ), memory and learning, language and executive skills, and behaviour. Sixteen of the children were found to have been in the supplemented group and 21 in the unsupplemented group. Results: Children who had been in the supplemented group performed better in all modalities tested than those from the unsupplemented group. The differences were statistically significant (analysis of variance) for motor function, performance IQ, the general memory index, and behaviour as assessed by the children's parents. The supplemented children outperformed the unsupplemented controls by 10% in all three components of the memory and learning tests (difference not significant but p < 0.1 for each) and in language function (p < 0.05 for object naming) and educational attainment (p < 0.05 for arithmetic age). Conclusions: Infants born at or before 33 weeks gestation require a higher sodium intake in the first two weeks of postnatal life than those born at or near term, and failure to provide such an intake (4–5 mmol/day) may predispose to poor neurodevelopmental outcome in the second decade of life

Neurotoxicity in lymphoblastic leukaemia: comparison of oral and intramuscular methotrexate and two doses of radiation.

Serial cranial computed tomograms were carried out in 136 children with acute lymphoblastic leukaemia who were receiving 24 Gy or 18 Gy of cranial irradiation and continuing treatment with doses of methotrexate given weekly orally or intramuscularly. The findings were correlated with treatment variables, the development of fits, and the intelligence quotient (IQ). Reversible brain shrinkage, attributed to treatment with steroids, was found on 87 of 114 initial scans (76%); 14 showed changes in white matter during treatment (10%), and calcification was found in 13 either during or after treatment (10%). Eight children (6%) had fits, and in six of the eight there were changes in white matter or calcification on the scans. Comparison of the two radiotherapy dosages showed no difference in the incidence of abnormalities seen on computed tomography, fits, or serial IQ measurements, but children receiving intramuscular methotrexate had a higher incidence of calcification and a lower mean IQ at one year than those who received the drug orally, although this difference was not apparent later. Younger children were more likely to develop changes on computed tomograms and fits, and to have low IQs on completion of treatment, with changes most apparent in those less than 2 years of age. There were highly significant correlations between abnormalities on computed tomography, fits, and IQ. These findings confirm the neurological vulnerability of younger children with acute lymphoblastic leukaemia, show an association between abnormalities on computed tomography and intellectual deficit, and suggest that methotrexate is more toxic when given intramuscularly than orally. They provide no evidence that 18 Gy of cranial irradiation is less toxic than 24 Gy, and indicate the need for alternative treatment regimens

FOXP2 is not a major susceptibility gene for autism or specific language impairment

The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment