This article exemplifies the AAFP 2005 Annual Clinical Focus on the legal, social, clinical, and ethical issues of medical genomics.

To complement the 2005 Annual Clinical Focus on medical genomics, AFP will be publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the kind of care they might require in the future. The second review in this series discusses fetal alcohol syndrome and fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are caused by the effects of maternal alcohol consumption during pregnancy. Fetal alcohol syndrome (FAS) is the most clinically recognizable form of FASD and is characterized by a pattern of minor facial anomalies, prenatal and postnatal growth retardation, and functional or structural central nervous system (CNS) abnormalities. The consequences are lifelong, and the behavioral and learning difficulties are often greater than the degree of neurocognitive impairment. Alcoholrelated neurodevelopmental disorder also is a clinically recognizable diagnosis in the continuum of FASD and describes the clinical outcome when the facial features typical of FAS are absent.

Epidemiology Jump to section + Abstract

Epidemiology

Clinical Presentation

Diagnosis

Causes of Fetal Alcohol Spectrum Disorders

Referral and Management

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References FASD may affect up to 1 percent of the U.S. population.1,2 Birth defects related to these disorders can be prevented by avoiding alcohol ingestion during pregnancy. Although FASD is more strongly associated with higher levels of alcohol consumption compared with lower levels, animal studies have suggested that even a single episode of consuming the equivalent of two alcoholic drinks during pregnancy may lead to loss of fetal brain cells (one drink = 12 oz of beer, 5 oz of wine, or 1.5 oz of “hard” liquor).3 Despite widespread knowledge of alcohol’s deleterious effects, a study4 of women between 18 and 44 years of age showed that 10 percent used alcohol during pregnancy and that 2 percent engaged in “binge drinking” (i.e., five or more drinks on one occasion). Maternal factors that increase the risk of FASD include being older than 30 years, a history of binge drinking, and low socioeconomic status.5

Clinical Presentation Jump to section + Abstract

Epidemiology

Clinical Presentation

Diagnosis

Causes of Fetal Alcohol Spectrum Disorders

Referral and Management

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References Clinical findings in a newborn with FAS include a characteristic pattern of facial anomalies,6,7 with short palpebral fissures, a thin upper lip, and a long, smooth philtrum (Figures 1,2a through 2d, and 3a through 3c).4,8 Other findings may include a flat midface, ptosis of the eyelids, epicanthal folds, an upturned nose with a flat nasal bridge, underdeveloped ears (“railroad track” appearance, Figure 4), clinodactyly of the fifth fingers (Figure 5), camptodactyly, “hockey stick” palmar creases (Figure 5), hirsutism, and cardiac defects. Prenatal or postnatal growth retardation typically results in a height or weight below the 10th percentile for age and race. Microcephaly is common, as are structural brain anomalies. CNS impairment may not be apparent in newborns. Cognitive deficits and behavioral anomalies such as attention-deficit/hyperactivity disorder typically become more apparent in school-aged children with FASD and usually persist into adolescence and adulthood, whereas facial findings among the subset with FAS may become less characteristic. View/Print Figure Figure 1. Characteristic facial features in a child with fetal alcohol spectrum disorders. Findings may include a smooth philtrum, thin upper lip, upturned nose, flat nasal bridge and midface, epicanthal folds, small palpebral fissures, and small head circumference. Figure 1. Characteristic facial features in a child with fetal alcohol spectrum disorders. Findings may include a smooth philtrum, thin upper lip, upturned nose, flat nasal bridge and midface, epicanthal folds, small palpebral fissures, and small head circumference. View/Print Figure Figure 2. Characteristic facial features in children of different ethnicities with fetal alcohol spectrum disorders. (A) Child of Northern European descent. (B) Native American child. (C) Black child. (D) Biracial child (white, black). Figure 2. Characteristic facial features in children of different ethnicities with fetal alcohol spectrum disorders. (A) Child of Northern European descent. (B) Native American child. (C) Black child. (D) Biracial child (white, black). View/Print Figure Figure 3. Lip-Philtrum Guide. (A) The smoothness of the philtrum and the thinness of the upper lip are assessed individually on a scale of 1 to 5 (1 = unaffected, 5 = most severe). The patient must have a relaxed facial expression, because a smile can alter lip thinness and philtrum smoothness. Scores of 4 and 5, in addition to short palpebral fissures, correspond to fetal alcohol syndrome. (B) Guide for white patients. (C) Guide for black patients. Figure 3. Lip-Philtrum Guide. (A) The smoothness of the philtrum and the thinness of the upper lip are assessed individually on a scale of 1 to 5 (1 = unaffected, 5 = most severe). The patient must have a relaxed facial expression, because a smile can alter lip thinness and philtrum smoothness. Scores of 4 and 5, in addition to short palpebral fissures, correspond to fetal alcohol syndrome. (B) Guide for white patients. (C) Guide for black patients. View/Print Figure Figure 4. Characteristic features of an ear of a child with fetal alcohol spectrum disorders. Note the underdeveloped upper part of the ear parallel to the ear crease below (“railroad track” appearance). Figure 4. Characteristic features of an ear of a child with fetal alcohol spectrum disorders. Note the underdeveloped upper part of the ear parallel to the ear crease below (“railroad track” appearance). View/Print Figure Figure 5. Characteristic features of a hand of a child with fetal alcohol spectrum disorders. Note the curved fifth finger (clinodactyly) and the upper palmar crease that widens and ends between the second and third fingers (“hockey stick” crease). Figure 5. Characteristic features of a hand of a child with fetal alcohol spectrum disorders. Note the curved fifth finger (clinodactyly) and the upper palmar crease that widens and ends between the second and third fingers (“hockey stick” crease).

Diagnosis Jump to section + Abstract

Epidemiology

Clinical Presentation

Diagnosis

Causes of Fetal Alcohol Spectrum Disorders

Referral and Management

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References Diagnosis of FASD should be considered based on the clinical presentation or suspicion of maternal alcohol exposure. The Centers for Disease Control and Prevention diagnostic criteria for FAS require three specific facial findings (i.e., smooth philtrum, thin vermilion border of the upper lip, and short palpebral fissures), growth deficits, and CNS abnormalities (Table 14 and Figure 3). In the absence of characteristic facial findings, the diagnosis of FASD still should be considered in children with growth problems, CNS abnormalities, and a history of prenatal alcohol exposure. View/Print Table TABLE 1 Diagnostic Criteria for Fetal Alcohol Syndrome Clinical feature Criteria Shortened palpebral fissures ≤10th percentile for age and racial norms Smooth philtrum Score of 4 or 5 on Lip-Philtrum Guide (Figure 3) Thin vermilion border of upper lip Score of 4 or 5 on Lip-Philtrum Guide TABLE 1 Diagnostic Criteria for Fetal Alcohol Syndrome Clinical feature Criteria Shortened palpebral fissures ≤10th percentile for age and racial norms Smooth philtrum Score of 4 or 5 on Lip-Philtrum Guide (Figure 3) Thin vermilion border of upper lip Score of 4 or 5 on Lip-Philtrum Guide Because of the associated guilt or stigma, direct questioning or commonly used screening questionnaires such as the four-item CAGE criteria9 (Cut down, Annoyance, Guilt, Eye-opener) may fail to identify women at risk for delivering a child with FASD. One study10 showed the T-ACE (Tolerance, Annoyance, Cut down, Eye-opener) assessment to be more effective than other screening tools (Table 210,11). View/Print Table TABLE 2 T-ACE: Questions for Screening Pregnant Women for Alcohol Misuse Tolerance: How many drinks does it take to make you feel high? Annoyance: Have people annoyed you by criticizing your drinking? Cut down: Have you ever felt you ought to cut down on your drinking? Eye-opener: Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover? Score 2 points for a response of at least six drinks (either beer or mixed drinks) or one bottle of wine to the first question; 1 point is given for a positive response to the other questions. A score of 2 or more identifies 90 percent of women at risk for alcohol misuse. TABLE 2 T-ACE: Questions for Screening Pregnant Women for Alcohol Misuse Tolerance: How many drinks does it take to make you feel high? Annoyance: Have people annoyed you by criticizing your drinking? Cut down: Have you ever felt you ought to cut down on your drinking? Eye-opener: Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover? Score 2 points for a response of at least six drinks (either beer or mixed drinks) or one bottle of wine to the first question; 1 point is given for a positive response to the other questions. A score of 2 or more identifies 90 percent of women at risk for alcohol misuse.

Causes of Fetal Alcohol Spectrum Disorders Jump to section + Abstract

Epidemiology

Clinical Presentation

Diagnosis

Causes of Fetal Alcohol Spectrum Disorders

Referral and Management

Resources

References FASD is nonhereditary; alcohol causes neuronal damage and cell loss in the fetal brain through direct action as a toxin. No prenatal period has been shown to be safe from the deleterious effects of alcohol. CNS damage may result from alcohol exposure in any trimester, even before the time of a pregnancy test. Women should be advised not to drink from the time of conception to birth. Although FASD is not inherited, there seems to be a genetic predisposition to problem drinking. For example, in some persons of shared ancestry, such as Native Americans, the similarity in function of shared versions (alleles) of the gene that encodes alcohol dehydrogenase may contribute to an increased risk for alcohol dependence.12 Additionally, twin studies document similar outcomes in identical twins and different outcomes in nonidentical twins.6