Classical lissencephaly associated with dolichocephaly, hair and nail defect.

We report on an 1-day-old boy with classical lissencephaly (grade 1, according to Kato and Dobyns, 2003) associated with an extended phenotype, including dolichocephaly, and hair and nail defects. The diagnosis of lissencephaly was made in utero, allowing the rapid characterization of the phenotype at birth. Because previously reported cases were not associated with the features described in our proband, they might represent a newly identified condition.

Global developmental delay, osteopenia and ectodermal defect: a new syndrome.

UNLABELLED: Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation). SETTING: Tertiary care hospital. PATIENTS: Three children (two male siblings, and one unrelated girl). METHODS: We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.

A cost-utility analysis of low-dose hormone replacement therapy in postmenopausal women with an intact uterus.

OBJECTIVE: The objective of this study was to evaluate the cost utility of one year's treatment with a low-dose conjugated estrogen/medroxyprogesterone acetate (CE/MPA low dose) preparation (Premique Low Dose [Wyeth Pharmaceuticals, Maidenhead, UK]), compared with a higher-dose preparation (Premique; CE/MPA [Wyeth Pharmaceuticals, Maidenhead, UK]), in postmenopausal women with an intact uterus. The evaluation captured the resource implications associated with the difference in treatment discontinuation and adverse event driven consultations in patients receiving either the low- or higher-dose preparation. This economic evaluation was conducted from the perspective of the NHS. RESEARCH DESIGN AND METHODS: A health economic model was developed to calculate the incremental cost per quality-adjusted life year (QALY) gained from treatment with a lower-dose CE/MPA combination, compared with a higher-dose CE/MPA preparation. Cohorts of 100 patients were assumed to receive either CE/MPA low dose or CE/MPA for one year. A probabilistic sensitivity analysis was used to explore whether the base case model was robust to the assumptions employed. Neither costs nor consequences were discounted because of the one year timeframe. RESULTS: In the base case, CE/MPA low dose dominates, i.e. it showed a greater health gain at a reduced cost, in both mild and severe symptom populations. These results were repeated in the sensitivity analysis, with the cost-effectiveness planes for both mild and severe symptom populations showing a greater utility at a reduced cost. CONCLUSIONS: CE/MPA low dose has been demonstrated to be a cost-effective treatment of estrogen-deficiency symptoms in postmenopausal women with an intact uterus. It has great potential for increasing the number of patients benefiting from relief of menopausal symptoms while also reducing the resource utilisation associated with managing the adverse effects associated with higher-dose HRT.