Nobuo Matsuura

These 62 patients with the Kabuki make-up syndrome (KMS) were collected in a collaborative study among 33 institutions and analyzed clinically, cytogenetically, and epidemiologically to delineate the phenotypic spectrum of KMS and to learn about its cause. Among various manifestations observed, most patients had the following five cardinal manifestations: 1) a peculiar face (100%) characterized by eversion of the lower lateral eyelid; arched eyebrows, with sparse or dispersed lateral one-third; a depressed nasal tip; and prominent ears; 2) skeletal anomalies (92%), including brachydactyly V and a deformed spinal column, with or without sagittal cleft vertebrae; 3) dermatoglyphic abnormalities (93%), including increased digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; 4) mild to moderate mental retardation (92%); and 5) postnatal growth deficiency (83%). Thus the core of the phenotypic spectrum of KMS is rather narrow and clearly defined. Many other inconsistent anomalies were observed. Important among them were early breast development in infant girls (23%), and congenital heart defects (31%), such as a single ventricle with a common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta, patent ductus arteriosus, aneurysm of aorta, transposition of great vessels, and right bundle branch block. Of the 62 KMS patients, 58 were Japanese, an indication that the syndrome is fairly common in Japan. It was estimated that its prevalence in Japanese newborn infants is 1/32,000. All the KMS cases in this study were sporadic, the sex ratio was even, there was no correlation with birth order, the consanguinity rate among the parents was not high, and no incriminated agent was found that was taken by the mothers during early pregnancy. Three of the 62 patients had a Y chromosome abnormality involving a possible common breakpoint (Yp11.2). This could indicate another possibility, i.e., that the KMS gene is on Yp11.2 and that the disease is pseudoautosomal dominant. These findings are compatible with an autosomal dominant disorder in which every patient represents a fresh mutation. The mutation rate was calculated at 15.6 X 10(6).

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

IN 1960, Sutherland et al.1 reported on children with familial nongoitrous cretinism born of a hypothyroid mother with Hashimoto's disease. Subsequently, Goldsmith et al.2 studied this family in detail and concluded that the transplacental transfer of an unidentified thyrosuppressive factor or factors might have caused congenital thyroid suppression (partially reversible) in all six siblings. Neither the mechanism of this suppression, nor the nature of the thyrosuppressive factor, however, was clarified. In this paper, we describe two siblings with congenital transient hypothyroidism and a hypothyroid mother with Hashimoto's disease. Immunoglobulins that inhibited binding of thyroid-stimulating hormone (TSH)3 and did not contain . . .

OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.