Ian Walpole

Concerns about the safety of carbimazole in pregnancy were raised in 1985. Since this time many reports of children believed to have been affected by carbimazole in utero have appeared in the medical literature. Initial reports were of an increased incidence of scalp defects in the infants of treated mothers, but many other anomalies have now been described. Choanal atresia, gastrointestinal anomalies-particularly esophageal atresia, athelia/hypothelia, developmental delay, hearing loss, and dysmorphic facial features have all been reported. The phenotype associated with exposure to carbimazole appears to be rare but specific with distinctive facial features. We report on two new cases of carbimazole embryopathy with strikingly similar facial features.

CHARGE syndrome is an autosomal dominant condition that is caused by mutations in the CHD7 gene. Few familial cases of this syndrome have been reported and these were characterized by a wide clinical variability. We here report on five CHD7 mutation positive families and comment on their clinical features. We observed somatic and germline mosaicism as well as parent-to-child transmission of non-mosaic CHD7 mutations as causes of familial CHARGE syndrome. In one family with two affected sibs a somatic mutation was identified in lymphocytes of a clinically unaffected parent (2520G > A in exon 8). This is the second report of somatic CHD7 mosaicism in an unaffected parent. In two further families with affected siblings, we could not detect the mutation in parental lymphocytes suggesting germline mosaicism. The previously reported clinical variability was strikingly present in all five families. We find that alterations in CHD7 can result in a very mild phenotype, characterized by only a few minor symptoms of the CHARGE syndrome clinical spectrum. Such a mild phenotype was present in two families that shared the same 6322G > A missense mutation. These two families showed parent-to-child transmission. Phenotypically milder forms of CHARGE syndrome have a higher risk of transmission to multiple family members.

STUDY OBJECTIVE: The aim was to investigate the effect of low or moderate alcohol consumption upon fetal outcome. DESIGN: This was a prospective randomised cohort study with mother and infant follow-up sample stratified on level of maternal alcohol intake. SETTING: A large maternity hospital in Western Australia. PARTICIPANTS: 2002 randomly selected pregnant women were recruited over a 3 year period for questionnaire survey (19 mothers refused participation). From 665 women in a stratified subsample selected on the basis of prepregnancy alcohol consumption, 605 newborns were available for study. INVESTIGATION AND MAIN RESULTS: All 2002 women completed a comprehensive questionnaire on demographic, lifestyle (including diet), health, and obstetric factors. Of the 665 mothers who were followed through pregnancy, 605 liveborns were available at birth for measurement and detailed clinical evaluation. Low to moderate prepregnancy maternal alcohol intake was not associated with any untoward effect upon weight, length, head circumference at birth, or clinical well-being as indicated by Apgar score, respiratory distress syndrome, and overall clinical state. Other factors, particularly nicotine, were of much greater importance. CONCLUSIONS: This study fails to show any significant relationship between low to moderate prepregnancy maternal alcohol intake and newborn clinical status. The outcome suggests that cautionary advice to pregnant women warning that any alcohol taken during pregnancy is potentially harmful to the fetus is inaccurate and therefore probably counterproductive.