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It is debatable whether Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) represent a single clinical entity with a variable degree of expression or two different entities, because both disorders share common clinical and radiological manifestations, including similar craniofacial characteristics, and defective bone mineralization. Since it was shown that heterozygous truncating mutations in NOTCH2 are responsible for both HCS and SFPKS, 37 patients with HCS and four patients with SFPKS are reported. To elucidate the clinical consequences of NOTCH2 mutations, we present detailed clinical information for seven patients with truncating mutations in exon 34 of NOTCH2, six with HCS and one with SFPKS. In addition, we review all the reported patients whose clinical manifestations are available. We found 13 manifestations including craniofacial features, acroosteolysis, Wormian bones, and osteoporosis in >75% of NOTCH2-positive patients. Acroosteolysis was observed in two patients with SFPKS and bowing fibulae were found in two patients with HCS. These clinical and molecular data would support the notion that HCS and SFPKS are a single disorder.

Objective: The aim of this study was to compare the efficacy and adverse reactions during initial treatment and longterm outcome between children and adolescents with Graves ' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI). Design, setting and participants: Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n = 64) and group P (PTU: n = 69) and into four subgroups by initial dose: group M1 ( < 0.75 mg/kg of MMI, n = 34), group M2 ( ≥ 0.75 mg/kg, n = 30), group P1 ( < 7.5 mg/kg of PTU, n = 24) and group P2 ( ≥ 7.5 mg/kg, n = 45). Main outcome measures:The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared. Results: Mean durations for normalization of T4 ( ± SD) were 1.7 ± 1.0 months in group M and 2.3 ± 2.4 in group P [not signifi cant (NS)], while the mean duration in group P1 (3.1 ± 3.3) was signifi cantly longer than those in the other subgroups (M1: 1.9 ± 1.2; M2: 1.4 ± 0.7; P2; 1.7 ± 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0 % of cases in group M and 31.9 % in group P (NS). The incidence in group P2 (44.4 % ) was signifi cantly higher than those in group M1 (20.6 % ) and group P1 (8.3 % ). Remission rates did not differ between the MMI-treated group (35.0 % , n = 20) and PTU-treated group (50.0 % , n = 40). Conclusions: PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Abstract.We examined clinical, endocrinological and molecular biological aspects of an estrogen-secreting adrenal carcinoma in an 18-month-old male to clarify the pathogenesis of this condition.An 18-month-old boy was referred for evaluation of progressive bilateral gynecomastia and appearance of pubic hair. The patient had elevated plasma estradiol (349 pg/ml) and testosterone (260 ng/dl) levels that completely suppressed FSH and LH levels, and was subsequently diagnosed with an adrenal tumor on the right side. After removal of a 300-g adenocarcinoma, gynecomastia regressed and essentially normal hormone levels were restored.Aromatase activity in the tumor tissue determined by the 3H-water method was 71.0-104.4 pmol/min/mg protein.High levels of aromatase protein and mRNA in the tumor tissue were also demonstrated, while neither aromatase activity nor protein was detected in normal adrenal glands. To investigate the regulation of aromatase expression in the adrenal carcinoma, we examined the usage of alternate promoters responsible for aromatase gene transcription.In the present case, the amounts of aromatase mRNA utilizing gonadal types of exon lc (I.3) and id (II) were significantly higher than those that using other exon is. This result suggested that the utilization of a gonadal-type exon 1 might be involved in the overproduction of aromatase in estrogen-secreting adrenal carcinoma.