Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russeli syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.

Review of 20 patients with glucocorticoid deficiency (three cases also with salt loss) associated with absent tear secretion (19 cases) and sensory neuropathy have also been described,89 together with ataxia, optic atrophy and impaired intelligence, "I indicating that the disorder has a wide spectrum of clinical manifestations. This paper describes the findings in a multicentre collaborative study carried out to ascertain the incidence of disordered neurological and automatic funciton in the syndrome. MethodsIn order to obtain information on patients with the adrenal insufficiency/alacrima/achalasia syndrome in the UK, questionnaires were sent to 39 senior members of the British Society for Paediatric Endocrinology asking for information on any cases under their care. Thirty seven questionnaires were returned, and six cases with the disorder were identified in the UK (cases 4, 5, 6, 13, 15, 17 described below).To increase the number of patients available for study, members of the European Society for Paediatric Endocrinology known to have had patients with the disorder under their care were invited to participate in the study and were sent questionnaires asking for information on the presence of adrenal insufficiency, alacrima, achalasia of the cardia, abnormal neurological findings, tests of autonomic function, evidence of intellectual impairment, skin manifestations, and family history.In some families siblings have died in early infancy, probably as a result of adrenal insufficiency. These have not been included in the study as little information is available on their neurological status.

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.

The patterns of length alterations in the hand bones in cases of pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), and acrodysostosis were evaluated. The length of each of the hand bones was measured and compared to appropriate means for age and sex. The pattern profiles thus generated showed that those for PHP and PPHP are almost identical, and are similar to that seen in acrodysostosis, except for the much smaller size of the bones seen in the latter condition. PHP and PPHP are probably differend manifestations of the same entity, and acrodysostosis may also be related to them. Brachydactyly E is indistinguishable radiologically from the PHP-PPHP syndrome.

The correlations for stature between parents and grown-up offspring in 90 normal males and 116 normal females have been compared with similar correlations obtained in 27 adult males with Klinefelter's syndrome, 33 adult females with Turner's syndrome and in 75 adult patients with Down's syndrome. There was close similarity between the findings in the patients with sex chromosomal disorders and in normal subjects, a roughly constant amount of height being gained or lost through the chromosomal abnormalities. However the genetic pattern was lost in patients with Down's syndrome. In males with idiopathic precocious puberty and in untreated females with congenital adrenal hyperplasia, the parent-offspring correlations were not normal. In females with idiopathic precocious puberty they approximated normal values. The first two are pathological conditions of varying severity, whilst the majority of girls diagnosed as suffering from precocious puberty represent the extreme variant of normal.