Significant phenotype variability of congenital central hypoventilation syndrome in a family with polyalanine expansion mutation of the PHOX2B gene.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder resulting from mutations in the PHOX2B gene located on chromosome 4p12.3, characterized by hypoventilation secondary to missing responses to both hypercapnia and hypoxia. CASE REPORT: Proband. A girl, hospitalised 5 times for respiratory failure from 6 weeks old, presented at 4 years of age severe cyanosis related to pneumonia. Tracheostomy was done, and she was discharged home using a portable positive pressure ventilator during sleep. Proband's father: The father was retrospectively found out to suffer from severe headache and excessive daytime sleepiness. Molecular genetic evaluation of PHOX2B gene was performed and casual polyalanine repeat expansion mutation c.741_755dup15 in exon 3 was found both in proband and her father in heterozygous form. The proband's grandmother died of respiratory failure after administration of benzodiazepine at the age of fifty years. Considering the grandmother's history, she is highly suspected of having had CCHS as well. CONCLUSION: Repeated respiratory failure of girl was explained by PHOX2B mutation and Ondina curse. Proband´s father has incompletely penetrated PHOX2B heterozygous mutation as well and proband´s grandmother died probably from the consequences of drug interaction with PHOX2B mutated background as well. Both daughter and father currently require overnight mechanical ventilatory support. Although most PHOX2B mutations occur de novo, our case is a rare three generation family affected by autosomal dominant inheritance with incomplete penetrance manifested as the late-form of CCHS and proven PHOX2B mutation in two generations.

Obesity, hypertension and insulin resistance in childhood--a pilot study.

BACKGROUND: Obesity and arterial hypertension are a serious risk factor for insulin resistance patients leading to diabetes and other disorders. Obesity is one of the most common nutritional problems in developed countries. Actually the incidence of obesity is increasing considerably, obesity is emerging in alarming rates between the last 10 years. Obesity and hypertension beginning in childhood often precedes the hyperinsulinemic state. The metabolic syndrome is rapidly increasing in prevalence with rising childhood obesity and sedentary lifestyles worldwide. The aim of this study was to compare average levels of the homeostatic indices HOMA and QUICKI in obese children compared to healthy and hypertonic children in order to find convenient markers for insulin sensitivity in clinical pediatric practice. METHODS: 49 obese children (11 girls, 38 boys), 42 children healthy (33 boys and 9 girls) and 37 hypertensive children (4 girls, 33 boys) were selected. RESULTS: The average level of HOMA in obese children was 4.58; in healthy children 1.8 and in the group of hypertonic children the level was 2.75. The average level of QUICKI in obese children was 0.22; in healthy children 0.29 and in hypertonic children 0.28. CONCLUSIONS: The results demonstrate the possibility of insulin sensitivity assessment using these indices in pediatric practice. QUICKI has a narrower confidence interval and thus a lower variability. QUICKI an HOMA indexes are useful predominantly for epidemiological purposes, mainly for maping the scope of insulinoresistance among children.

Obesity and insulin resistance in childhood.

Obesity is a serious risk factor for insulin resistance leading to diabetes and other disorders. As it is also occurring at ever younger age groups the aim of this study was to compare average levels of the homeostatic indices HOMA and QUICKI in obese compared to healthy children in an effort to find convenient markers for insulin sensitivity in clinical pediatric practice. Twenty one obese and 29 healthy children were selected. The average level of HOMA in obese children was 3.6, in healthy children 1.7 while the average level of QUICKI in obese children was 0.33 and in healthy children 0.36. The results demonstrate the possibility of insulin sensitivity assessment using these indices in pediatric practice. QUICKI has a narrower confidence interval and thus lower variability.

Single umbilical artery and its siding in the second trimester of pregnancy: relation to chromosomal defects.

OBJECTIVES: To determine the possible association between single umbilical artery (SUA) in the second trimester of pregnancy and the incidence of chromosomal abnormalities. To determine whether the presence of chromosomal defects in fetuses with SUA is related to the side of the missing artery. METHODS: Color flow imaging of the fetal pelvis was used to determine the number of umbilical arteries in 2147 fetuses immediately before amniocentesis for karyotyping in the second trimester of pregnancy. RESULTS: SUA was diagnosed in 102/2147 (4.8%) cases. The left umbilical artery was absent in 60/102 (58.8%) fetuses, compared with the 42/102 (41.2%) for the right artery. The rate of chromosome abnormalities was significantly higher among fetuses with SUA than among those with 2 umbilical arteries (19/102 or 18.6% versus 109/2045 or 5.3%; OR = 4.1, 95% CI 2.3-7.1, p < 0.0001). Among fetuses with SUA, there was no significant difference in the rate of chromosome abnormalities between those with absence of the left versus the right artery (11/60 or 18.3% versus 8/42 or 19.0%, p = 0.93). There was an SUA in 5/39 (12.8%) cases with trisomy 21, 8/16 (50%) with trisomy 18, 1/4 (25%) with trisomy 13 and 5/69 (7.2%) with other chromosomal defects. There were no chromosome abnormalities in fetuses where a single umbilical artery was an isolated sonographic finding. All fetuses with SUA and chromosomal defects had associated abnormalities detected by ultrasound. CONCLUSION: A single umbilical artery (SUA) in the second trimester of pregnancy has a high association with trisomy 18, 13, 21 and other chromosomal defects, but all chromosomally abnormal fetuses had associated malformations detected by ultrasound. The absence of the left artery is more frequent than the absence of the right artery. The association with chromosomal abnormalities seems to be equal on each side.