Normal development of the cerebral cortex requires long-range migration of cortical neurons from proliferative regions deep in the brain. Lissencephaly ("smooth brain," from "lissos," meaning smooth, and "encephalos," meaning brain) is a severe developmental disorder in which neuronal migration is impaired, leading to a thickened cerebral cortex whose normally folded contour is simplified and smooth. Two identified lissencephaly genes do not account for all known cases, and additional lissencephaly syndromes have been described. An autosomal recessive form of lissencephaly (LCH) associated with severe abnormalities of the cerebellum, hippocampus and brainstem maps to chromosome 7q22, and is associated with two independent mutations in the human gene encoding reelin (RELN). The mutations disrupt splicing of RELN cDNA, resulting in low or undetectable amounts of reelin protein. LCH parallels the reeler mouse mutant (Reln(rl)), in which Reln mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity. RELN encodes a large (388 kD) secreted protein that acts on migrating cortical neurons by binding to the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor 2 (ApoER2; refs 9-11 ), alpha3beta1 integrin and protocadherins. Although reelin was previously thought to function exclusively in brain, some humans with RELN mutations show abnormal neuromuscular connectivity and congenital lymphoedema, suggesting previously unsuspected functions for reelin in and outside of the brain.

An investigation of the psychological characteristics of 44 children aged 6-16 years with documented evidence of idiopathic infantile hypercalcaemia revealed cognitive abilities and behavioural patterns which distinguish these children from other mentally handicapped groups. The children were all mildly to severely mentally handicapped, but exhibited superior verbal skills compared to their visuo-spatial and motor abilities. They showed high rates of behavioural disturbance, particularly in terms of hyperactivity, social isolation, anxiety, and eating and sleeping difficulties. Other aspects of behaviour, spoken language and personality that were commonly encountered are also described and quantified. From these observations approaches to remedial teaching are suggested.

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition. year, Black and Bonham Carter'2 noted that the

We propose that these charts be adopted for routine clinical practice as abnormalities in growth are an important feature of this syndrome.

SUMMARY A sample of 23 children aged seven to 12 years with diagnoses of infantile hypercalcaemia was assessed on a battery of psychological tests and rating scales in an attempt to describe the psychological characteristics of this disorder. All children were found to have a mild or moderate degree of mental handicap. As a group, their expressive language skills were superior to their verbal comprehension. They displayed a high degree of behaviour and emotional disorders, most notably in terms of high levels of activity. Most children were reported as being highly sensitive to noise. This study clarifies some of the psychological correlates of infantile hypercalcaemia and some implications for management are suggested. RÉSUMÉ Caractéristiques psychologiques de I'hypercalcémie infantile: une investigation préliminaire Une batterie de tests psychologiques et d'échelles de niveau a été proposée à un échantillon de 23 enfants, âgés de sept à 12 ans, chez qui avait été porté un diagnostic d'hypercalcémie infantile, dans le but de décrire les caractéristiques psychologiques de ce trouble. Un degré léger ou modéré de handicap mental a été observé chez tous les enfants. En tant que groupe, la capacité expressive du langage était supérieure à la compréhension verbale. Les enfants présentaient un degréélevé de troubles comportementaux et émotifs, tout spécialement en terme de haut niveau d'activité. Une haute sensibilité au bruit a été relevée chez la plupart des enfants. Cette étude précise quelques une des caractères psychologiques de I'hypercalcémie infantile et les auteurs suggérent quelques implications thérapeutiques. ZUSAMMENFASSUNG Die psychologischen Charakteristika der Hypercalcaemie im Sauglingsalter: eine vorläufige Untersuchung 23 Kinder im Alter zwischen sieben und 12 Jahren mit der Diagnose Hypercalcaemie im Säuglingsalter wurden anhand psychologischer Tests und Bewertungsskalen untersucht, um die psychologischen Charakteristika dieser Erkrankung herauszufinden. Alle Kinder hatten eine leichte bis mittelgradige geistige Behinderung. Als Gruppe war ihre expressive Sprache besser als ihr Wortverständnis. Sie zeigten im hohem Maße Verhaltens‐ und Gemütsstörungen, was sich besonders in Hyperaktivität äußerte. Von den meisten Kindern wurde berichtet, daß sie äußerst geräuschempfindlich seien. Diese Studie stellt einige psychologische Korrelate der Hypercalcaemie im Säuglingsalter dar und macht einige Vorschläge zu ihrer behandlung. RESUMEN Caractreristicas psicológicas de la hipercalcemia infantil: investigación preliminar Una muestra de 23 niños de siete a 12 años con el diagnóstico de hipercalcemia infantil fueron examinados con una bateria de tests psicológicos y escalas de porcentajes con el objeto de descnbir las caracteristicas psicológicos de esta alteratión. Se halló que todos los niños tenian una dificultad mental leve o moderada. Como grupos sus habilidades de lenquaje expresivo eran superiores a su comprensión verbal. Mostraban un alto grado de alteraciones emocionales y de conducta, sobre todo en tér...