Impaired neuromotor outcome in school-age children with congenital hypothyroidism receiving early high-dose substitution treatment.

Congenital hypothyroidism (CH) can lead to intellectual deficits despite early high-dose treatment. Our study aimed to determine whether motor impairments can occur despite early high-dose treatment. Sixty-three children with CH and early (median age of onset of treatment 9 d), high-dose treatment (median starting dose of levothyroxine 14.7 µg/kg/d) were tested with the Zurich Neuromotor Assessment (ZNA) at a median age of 13.8 y (range 7.0-14.2 y). Median z-scores in the children with CH were -0.95 in the pure and -0.56 in the adaptive fine motor component, significantly lower than in the ZNA test norms (p < 0.001 and p = 0.01, respectively). The 26 children with athyreosis were more affected than the 33 children with dysgenesis, particularly in the pure motor (-1.55 versus -0.76, p = 0.03), adaptive fine motor (-1.31 versus 0.13, p < 0.01), and static balance task (-0.47 versus 0.67, p = 0.01). Boys performed worse than girls. Older age at onset of treatment was related to poorer adaptive fine motor performance. Movement quality (assessed by associated movements) was not affected. We conclude that severe CH can cause neuromotor deficits persisting into adolescence. These deficits cannot completely be reversed by postnatal treatment, but earlier age at treatment may reduce the degree of impairment.

Aromatase deficiency owing to a functional variant in the placenta promoter and a novel missense mutation in the CYP19A1 gene.

CONTEXT: Aromatase deficiency in women is a rare 46, XX disorder of sex differentiation characterized by a defect in catalysing oestrogens from androgens. OBJECTIVE: To better understand this rare disorder, we searched for mutations in the CYP19A1 gene of an affected girl and analysed their functional consequences. DESIGN AND PATIENT: We examined a girl presenting with clitoral hypertrophy at birth and mild maternal virilization (acne) during pregnancy. MAIN OUTCOME MEASUREMENT: A genotype-phenotype correlation was found. RESULTS: By direct sequencing of the CYP19A1 gene, we identified a heterozygous A>G mutation (c. A1374G) mutation in exon IX, leading to the missense p.N411S in the P450Aro protein and a heterozygous placenta promoter variant -41 base pairs upstream of exon I.1. Aromatase enzyme activity was completely lost when the mutant p.N411S protein was expressed in COS-1 cells. The placenta promoter variant had a significantly reduced (-50%) transactivation ability compared to wild-type. CONCLUSION: Our data describe a novel loss-of-function missense mutation in CYP19A1 combined with the first-described variant of the placenta promoter with a significant reduction in function, likely to be the molecular basis of this rare 46, XX disorder of sex development. This seems to represent a unique case of aromatase deficiency occurring in utero only.

Pneumomediastinum in the neonatal and paediatric intensive care unit.

The incidence, aetiology and pathophysiology of pneumomediastinum (PM), an uncommon and potentially serious disease in neonates and children, were evaluated. A retrospective chart review of all patients diagnosed with PM who were hospitalised in the intensive care unit of the University Children's Hospital Zürich, Switzerland, from 2000 to 2006, was preformed. We analysed the incidence, severity and causes of PM and investigated the possible differences between neonatal and non-neonatal cases. Seven children and nine neonates were identified with PM. All patients had a good outcome. Six cases of PM in the group of children older than 4 weeks were deemed to be caused by trauma, infection and sports, whereas one case was idiopathic. All nine neonatal cases presented with symptoms of respiratory distress. We were able to attribute four cases of neonatal PM to pulmonary infection, immature lungs and ventilatory support. Five neonatal cases remained unexplained after careful review of the hospital records. In conclusion, PM in children and neonates has a good prognosis. Mostly, it is associated with extrapulmonary air at other sites. It is diagnosed by chest X-ray alone. We identified mechanical events leading to the airway rupture in most children >4 weeks of life, whereas we were unable to identify a cause in half of the neonates studied (idiopathic PM).