John T. Martsolf

Fetal alcohol syndrome: Diagnosis and syndromal variability

The diagnostic criteria for Fetal Alcohol Syndrome (FAS) are reviewed and the authors suggest a new diagnostic schema to allow for a more adequate description of the range of FAS. FAS is also reviewed by topic area. Associated problems believed to be caused by maternal alcohol ingestion are discussed.

FETAL ALCOHOL SYNDROME: MATERNAL AND NEONATAL CHARACTERISTICS

UNLABELLED Alcohol is the most common identifiable teratogenic cause of mental retardation in North America. Fetal Alcohol Syndrome (FAS) is a major public health problem, which is frequently under diagnosed by physicians. OBJECTIVE To identify and quantify the maternal risk factors and neonatal characteristics of children with FAS. DESIGN A retrospective case-control study using birth certificate data of North Dakota children diagnosed with FAS. Five controls were selected for each patient. Controls were selected from the computerized birth registry and matched by gender, year and month of birth. SUBJECTS AND SETTING A list of all the children diagnosed with FAS from the North Dakota FAS Registry was sent to the State Health Department. We were able to locate the birth certificates for 132 (56%) of the 228 cases on the registry. RESULTS Of the 132 FAS cases, 106 (80.3%) were Native Americans and 24 (18.2%) were Caucasians. In this sample 51 (38.6%) of the cases were male and 81 (61.4%) were female. Statistically significant maternal characteristics at p < 0.01 were: older mothers age, lower education level, fewer months of prenatal care, fewer prenatal visits, lower gestational age at time of delivery and less prenatal weight gain. Significant neonatal differences at p < 0.01 were lower birth weight and Apgar scores and higher incidence of congenital malformations. CONCLUSION FAS is a completely preventable developmental disability. Consumption of alcohol during pregnancy can result in lifelong physical and mental impairments on the fetus. All pregnant women should be screened for alcohol use during prenatal visits. Women with positive screens or at high risk should be identified early by the primary care physician and referred for treatment and counseling.

Partial 6p trisomy associated with infantile autism.

Partial trisomy 6p with duplications ranging from 6p21 to 6p25–pter is emerging as an established syndrome. We report a case of duplication of 6p (6p23–pter) and deletion of 2q37–qter. Features characteristic of 6p partial trisomy present in the patient are low birth‐weight, and mental and developmental retardation. Major facial features include prominent forehead, flat occiput, multiple ocular abnormalities, low‐set ears, prominent nasal bridge, long philtrum and small pointed mouth. Repeated examinations of the patient from birth to the age of over 5 years revealed that he has infantile autism. Since autistic children are generally not associated with chromosome anomalies, in view of the present case, it is suggested that karyotypic analysis be considered for such children. Where possible, extended study for autism in 6p trisomic children may also be desirable.

Increased sibling mortality in children with fetal alcohol syndrome

We compared the rate of all‐cause mortality in siblings of children diagnosed with fetal alcohol syndrome (FAS) with the siblings of matched controls. The siblings of children with FAS had increased mortality (11.4%) compared with matched controls (2.0%), a 530% increase in mortality. The age of death in case siblings deaths occurred later (between 1 day and 7 years) compared with the controls (1 day to 4 years) [odds ratio (OR) = 2.4 (0.4 ‐ 15.6)]. Siblings of children with FAS had increased risk of death due to infectious illness [OR = 13.7 (1.2 ‐ 361)] and sudden infant death syndrome compared with controls [OR = 10.2 (1.2 ‐ 75.1)]. A diagnosis of FAS is an important risk marker for mortality in the siblings of the proband even if they do not have FAS. Maternal alcoholism appears to be a useful risk marker for increased mortality risk in diagnosed cases and their siblings. This has important implications in the management of family members of children with FAS.

Fragile X Syndrome Associated with Tourette Symptomatology in a Male with Moderate Mental Retardation and Autism

ABSTRACT A case of fragile X syndrome and Tourette symptomatology in an 11-year-old mentally retarded male with autism is reported. The coexistence of these multiple disorders has apparently not been previously reported.

Mortality rates in subjects with fetal alcohol spectrum disorders and their siblings

BACKGROUND Our objective was to estimate the mortality rate in subjects with fetal alcohol spectrum disorders (FASD) and their siblings whose FASD status was unknown. METHODS We used the state FASD Registry to link subjects with FASD to a North Dakota birth certificate. We were able to link 304 of 486 cases (63%). We used the birth certificates to identify the mother and children born to the mother (siblings). We then searched for death certificates for both the FASD cases and their siblings. We then calculated the annual and age-adjusted mortality rates for the siblings of the Registry cases and compared them with mortality rates from North Dakota. RESULTS The FASD case mortality rate was 2.4%, with a 4.5% mortality rate for their sibings, accounting for 14% of all deaths when compared to the North Dakota residents matched by age and year of death. The sibling deaths accounted for 21.5% of all cause mortality matched by age and year of death. The age-standardized mortality ratios were 4.9 for the FASD cases and 2.6 for their siblings whose FASD status was unknown. CONCLUSIONS Mortality rates for FASD cases and their siblings were increased and represent a substantial proportion of all cause mortality in North Dakota. Prevention of FASD may be a useful strategy to decrease mortality.

Pitt-Rogers-Dank syndrome: The result of a 4p microdeletion

Pitt-Rogers-Danks syndrome (PRDS) is a rare, presumed autosomal recessive, syndrome with pre- and postnatal growth retardation, microcephaly, characteristic facial appearance, seizures, unusual palmar creases and developmental delay. Since the first description in 1984, only 7 cases have been reported. We report the identification of a 4p microdeletion in 2 new patients, who were previously diagnosed with PRDS, as well as the sibs in Pitt et al. [1984]. PRDS can no longer be considered autosomal recessive. Although our cases are attributable to a microdeletion in 4p16, it is uncertain if the critical region involves a single locus or multiple loci or to what extent this region overlaps with the critical region for Wolf-Hirschhorn syndrome.

The FAS Screen: a rapid screening tool for fetal alcohol syndrome

Fetal alcohol syndrome (FAS) is an important cause of mental retardation and developmental disabilities. A population based screening tool would allow for early diagnosis and entry into intervention programs. The aim of the study was to develop a brief screening tool for use in population‐based settings to improve the identification of children with FAS. The FAS Screen was developed and tested in six sites. These were sites that served children and all were located in North Dakota. Screening was completed on 1013 children, 65 were found to have a positive screening score and were referred for further investigation. Forty were seen for evaluation by a medical geneticist and six were diagnosed with FAS. The estimated values for the screening tool were: specificity 94.1%, sensitivity 100%, positive predictive value 9.1% and negative predictive value 100%. The cost of screening was

Children with Fetal Alcohol Syndrome in North Dakota: a case control study utilizing birth certificate data

13.00 per child and the cost per case identified was

Diagnosis of fetal alcohol spectrum disorders: a validity study of the fetal alcohol syndrome checklist

4,100. The FAS Screen is a brief screening test with acceptable performance characteristics and is cost effective.