Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect.

BACKGROUND: Patients with Xp22.3 interstitial and terminal deletions have been shown to be affected by intellectual disability (ID) or autism. Previously, VCX-A (variably charged protein X-A), located at Xp22.3, was introduced as a gene for ID and its presence was suggested to be sufficient to maintain normal mental development. Recent reports suggest that mutations in NLGN4 (neuroligin 4), located at that same region, are involved in autistic disorders and ID. METHODS: In the current case study, we clinically and molecularly describe a pedigree of three generations affected by contiguous gene syndrome that includes features of X-linked ichthyosis and Kallmann syndrome. RESULTS: Molecular analysis revealed the presence of an interstitial deletion spanning approximately 4.5Mb at Xp22.3. The centromeric breakpoint was localized between markers DXS1467 and DXS8051, proximal to KAL-1. The telomeric breakpoint was localized between markers DXS89 and DXS1060, distal to NLGN4. The deletion of VCX-A and NLGN4 in this family prompted us to examine the cognitive functions of our two adult patients using comprehensive intellectual and neurocognitive assessment. Normal intellectual function was found in one patient and mild ID was revealed in the other. Neither patient met any Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for a pervasive developmental disorder such as autism. CONCLUSIONS: These findings suggest that deletion of VCX-A and NLGN4 can result in variable phenotypic features and that normal mental development can be achieved despite this deletion, emphasizing the importance of environmental factors and possible modifier genes.

Early motor development of blind children.

OBJECTIVES: The purpose of this study was to assess the characteristic motor developmental pattern in blind children in Israel. METHODOLOGY: The study compared the developmental data concerning 10 motor skills of 40 blind children to a control group of sighted children and to the motor developmental milestones of the Bayley Developmental Scale and the Revised Denver Developmental Screening Test. RESULTS: The motor development of blind children was delayed, the delay being significant in all 10 motor skills that were examined. This delay emphasizes the major importance of vision as a sensory input modality for the process of sensory- motor development. CONCLUSION: An adequate stimulating environment and proper parental handling could potentially shorten the motor developmental delay but probably not eliminate it entirely.

Spontaneous language of children with specific neurological syndromes.

This paper presents data concerning the early phases of language development in 8 children with congenital neurological syndromes (NS) who are cognitively impaired. The children are native speakers of Hebrew, and their verbal achievements assessed on normative tests are below their age level. The children's spontaneous speech was analyzed with respect to 13 different language variables known to be diagnostic of a child's developmental level. No differences were found between the children and their language-matched controls on 10 grammatical variables. The groups differed, however, in number of pragmatic errors, errors of word choice, and errors of gender marking on animate nouns. Profile analysis was done through the use of POSAC (partial order scalogram analysis by base coordinates; Shye, 1985; Shye, Elizur, & Hoffman, 1994). The analysis did not reveal differences between the children with NS and the controls. These findings suggest the possibility of a mechanism that is functionally akin to brain plasticity. Such a mechanism will guarantee the preservation of basic linguistic skills in children with NS.

Inattention, hyperactivity and speech delay at 2-4 years of age as a predictor for ADD-ADHD syndrome.

In the Jerusalem Institute for Child Development children with various developmental disorders at ages of 0-5 years are examined. Thirty-six children aged 2-4 years were examined by us and were found to have inattention, hyperactivity and speech delay with an IQ or DQ above 70 and were reexamined at 7-14 years of age. They were compared to a group of 27 control children. All children had a complete neurodevelopmental examination using the Touwen & Prechtel examination for Minor Neurological Dysfunction. They also had a Pollack tapper test for the identification of learning disabilities and the Conners parent's and teacher's hyperactivity rating scales. Of the 36 children from the research group 20 studied in special education classes because of behavioral disorders, inattention, and severe learning disabilities. They all had ADD-ADHD. There were 16 children in regular schools, of whom 9 had ADD-ADHD. In the control group only one child had ADD-ADHD. A very high number of the research group children failed in 2 or all 3 tests used in this study in comparison to controls. It seems that "soft" neurological signs with hyperactivity, inattention and speech delay may be early clinical signs of ADD-ADHD as 80% of the children with these clinical features developed ADD-ADHD during early school age.

Reye's syndrome; diagnosis by muscle biopsy?

Three children with Reye's syndrome are described. One child died, the second had mild and transient illness, and the third had recurrent episodes. In all 3 children a muscle biopsy showed pronounced infiltration of the myofibres with fat microdroplets as shown by the oil red O stain and by electron microscopical examination. We suggest that needle biopsy of muscle may be a quick and safe aid to the diagnosis of Reye's syndrome, and may be preferable to liver biopsy in view of the pronounced tendency to bleed in Reye's syndrome.

Extramembranous pregnancy: maternal, placental, and perinatal implications.

The case of a patient who survived extramembranous pregnancy is presented, and the maternal, fetal, placental, and neonatal features of the condition are described and delineated. Previously underscribed phenomena include clinical evidence of fixed fetal position and a unique pattern of hemosiderin and hematoidin staining of the fetal membranes. The patient described had an intermediate form of the oligohydramnios tetrad following premature rupture of the membranes; the infant survived with respiratory support therapy in spite of apparent partial lung hypoplasia. On the basis of this and previous observations of the outcome of pregnancy complicated by prolonged amniotic fluid leakage, preliminary recommendations for the management of such pregnancies are made.