James W. Hanson

Maternal alcohol use and risk of orofacial cleft birth defects

Maternal alcohol use during pregnancy is a known cause of birth defects associated with the fetal alcohol syndrome, but its role in more common, isolated, craniofacial birth defects is not well understood. A population-based, case-control study of orofacial clefts was conducted in Iowa using births during 1987-1991. Cases were identified by the Iowa Birth Defects Registry and classified as having a cleft lip with or without cleft palate (CLP) or cleft palate only (CP) and whether the cleft was isolated or occurred with other birth defects. Controls were selected from normal Iowa births. Maternal alcohol use during pregnancy was classified according to self-reported drinks consumed per month. Results are based on 302 controls and the following numbers in each case group: 118 isolated CLP, 56 isolated CP, 51 CLP with multiple defects, and 62 CP with multiple defects. Compared to women who did not drink alcohol during pregnancy, the relative odds of isolated CLP rose with increasing level of maternal drinking as follows: 1-3 drinks per months, 1.5; 4-10 drinks per month, 3.1; more than 10 drinks per month, 4.7 (chi-square test for trend, P = 0.003). Adjustment for maternal smoking, vitamin use, education, and household income did not substantially alter these results. No significant association was found between alcohol use and isolated cleft palate or clefts in children with multiple birth defects. Alcohol use during pregnancy may be a cause of isolated cleft lip with or without cleft palate.

Shprintzen-Goldberg syndrome: a clinical analysis.

Shprintzen-Goldberg syndrome is one of a group of disorders characterized by craniosynostosis and marfanoid habitus. Eleven cases were reported previously. We present 4 new patients and review one of the patients of the original report of Shprintzen and Goldberg [1982: J Craniofac Genet Dev Biol 2:65-74], 15 years later. The clinical and radiologic findings on our patients are compared with those of the previously reported patients and also with those of Furlong et al. [1987: Am J Med Genet 26:599-604] and Lacombe and Battin [1993: Clin Dysmorphol 2: 220-224], who share many of the characteristics of Shprintzen-Goldberg syndrome. Some of the clinical data are helpful in determining if the patients of Furlong et al. [1987: Am J Med Genet 26:599-604] and Lacombe and Battin [1993: Clin Dysmorphol 2: 220-224] have a separate syndrome or represent a variant of Shprintzen-Goldberg syndrome. However, radiologic investigations appear to be more specific, since an abnormality of the first and second cervical vertebrae, hydrocephalus, dilatation of the lateral ventricles, and a Chiari-I malformation of the brain were found only in the patients with Shprintzen-Goldberg syndrome. The apparently diagnostic findings of the 15 patients with this syndrome may be helpful in differentiating between Shprintzen-Goldberg syndrome and other syndromes with craniosynostosis and marfanoid habitus.

Psychometric Studies in Muscular Dystrophy Type Ilia (Duchenne)

Mental retardation is found in about one‐third of the cases of muscular dystrophy type Ilia. It is present already in the early phases of the disease and remains essentially unchanged as the muscular condition progresses. It is concluded that mental retardation is an intrinsic manifestation of the mutant gene, which, however, shows a limited expressivity. Occasionally neglect and cultural deprivation of the severely disabled child may represent an additional environmental cause of mental retardation.

The effect of follow-up on limiting non-participation bias in genetic epidemiologic investigations

The use of a comprehensive follow-up strategy to limit non-participation bias was evaluated in a population-based case-control study of orofacial clefts. Birth parents were requested to provide exposure data, and index children and parents were asked to provide blood specimens. Follow-up included telephone or postal reminders every two weeks for up to three months. Consent to participate was received from 281 (76.6%) case mothers and 246 (72.4%) case fathers. The corresponding totals for controls were 279 (54.7%) and 245 (49.8%). Evaluation of participation rates by intensity of follow-up showed that 23% of case and 18% of control families consented without reminders (first stage); 81% of cases and 83% of controls agreed following one or two reminders (second stage); and the remainder of participants consented following three or more reminders (final stage). Cumulative distributions of sociodemographic characteristics differed little between second and final stage participants. Odds ratios for maternal multivitamin use were similar between second and final stage participants, whereas those for maternal and paternal smoking tended to decline. Although follow-up measures were necessary to enroll most families, use of more than two reminders did not appear to increase the representativeness of the sample; however, termination of recruitment after only two reminders would have led to different conclusions. Future studies require data collection protocols that encourage participation from all population subgroups, and one alternative is presented.

Clinical Management Issues in Males with Sex Chromosomal Mosaicism and Discordant Phenotype/Sex Chromosomal Patterns

The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.

Moral and religious influences on the amniocentesis decision

Abstract As early as 1973 Fletcher documented moral problems families encountered as they struggled with the decision of whether or not to have amniocentesis. In this study we asked 202 women accepting and 50 women rejecting amniocentesis extensive questions about religious beliefs, behaviors, and beliefs about abortion. Members of small Protestant denominations were the most conservative. Catholics and other Protestants were intermediate with smaller differences between these middle groups. Those respondents claiming no religion or one of a non‐Christian denomination were the most liberal. Net predictors of acceptance of amniocentesis included respondents’ support for laws permitting abortion for medical reasons, negative responses about belief in the sanctity of life, having insurance, and the respondents’ political affiliation. Education and religious attendance were the most consistent net predictorsof moral attitudes. We concluded that the amniocentesis decision is influenced by many religious belief...

Rieger's Syndrome: A Case Report With a 15-Year Follow-up

A 15-year follow-up examination of a boy with Riegers syndrome showed that the anterior segment changes in this disease may be slowly progressive in the absence of glaucoma or miotic treatment. The patient also had two recently recognized systemic features of the syndrome, umbilicus cutis and hypospadias.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. birth defects and developmental disorders

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Fortuitous detection of a sporadic carrier of Duchenne's muscular dystrophy

SummaryA case is presented of a 19-year-old white female, detected while we were investigating the range of serum creatine kinase levels in “normal” controls. She presented elevated serum creatine kinase, myopathic electromyogram, and electron microscopic evidence of dystrophic changes in muscle tissue, but no clinically detectable muscular weakness. The significance of these findings is discussed. We felt that she was probably a sporadic carrier of the gene for Duchennes muscular dystrophy and, because there was no family history of neuromuscular disease, that this was the result of a spontaneous mutation.