BASICS
DESCRIPTION
• Fetal Alcohol Syndrome (FAS) is the most severe end on the continuum known as Fetal Alcohol Spectrum Disorders (FASD), an umbrella term that encompasses the adverse effects to developing fetuses from alcohol exposure in utero.
• With the proposed clarifications to the Institute of Medicine’s 1996 diagnostic criteria, children with FAS must fulfill 3 domains. Growth retardation (≤10th percentile for height or weight), facial anomalies that satisfy ≥2 of the 3: short palpebral fissures, thin vermilion border of upper lip and smooth philtrum, and lastly central nervous system abnormalities (structural or small head circumference).
• The presence or absence of maternal alcohol exposure divides FAS into 2 subcategories (1)[A]: FAS with confirmed maternal alcohol exposure and FAS without confirmed maternal alcohol exposure.
• Further, partial FAS characterizes those who satisfy the aforementioned facial malformations but have anomalies in only 1 of the other domains (CNS function/structure or growth).
EPIDEMIOLOGY
Incidence
With 4 billion babies born worldwide every year with in utero ethanol exposure, an estimated 1000–6000 have FAS (2)[C].
Prevalence
0.5–2.0 cases per 1000 live births (2)[C].
RISK FACTORS
• Consuming ≥1 drinks per day or binges of >5 drinks each episode (3)[C]
• Threshold not clearly defined because even 0.5 drink daily has been linked to adverse outcomes
Genetics
• High recurrence rates in siblings
• Higher rates have been detected for African Americans and Native Americans vs. non-Hispanic whites
• Different genotypes of alcohol dehydrogenase 1B (ADH1B), a gene (2)[A] which encodes the enzyme that catalyzes the breakdown of ethanol to acetaldehyde, has been found to carry unique risks for FAS.
• Most studies on ADH1B found a higher risk of alcohol-caused birth defects when the fetal genotype is homozygous for a particular at risk allele. The same genotype was also associated with a higher drinking frequency at conception. This does not explain the higher FAS occurrence in African Americans and Native Americans, the groups that have lower prevalence of the genotype.
• Another ADH1B allele seems to be a protective factor.
• Sequence variation in the cytochrome P450 E1 (CYP2E1) gene, which is involved in ethanol metabolism, has been suggested to yield a higher risk for FAS, even after adjusting for alcohol intake.
GENERAL PREVENTION
• FAS is entirely preventable (4)[A] if the pregnancy is alcohol-free. A strong predictor of alcohol use during pregnancy is consumption prior to conception.
• The U.S. Preventive Services Task Force recommended screening and behavioral counseling interventions in the primary care setting to lower alcohol abuse.
PATHOPHYSIOLOGY
• Mechanisms not well understood and most knowledge based on animal studies (5)[C]
• Craniofacial manifestations of FAS are likely due to teratogenic effects of ethanol and/or its metabolites such as acetaldehyde, before or during gastrulation and neurulation.
• Alcohol intoxication induces oxidative stress with production of free radicals and disturbance of antioxidant activities.
• Immunocytochemical assays performed with bromouridine incorporated into ethanol-exposed rats’ retina and optic nerve demonstrated diminished transcription activity in the eye tissues.
ETIOLOGY
• Prenatal exposure to alcohol, a proven teratogen
• Polymorphisms in certain genes may predispose the growing fetus to FAS.
COMMONLY ASSOCIATED CONDITIONS
• Poor adaptive and communication skills, including poor understanding of social cues and registering information in social contexts (6)[A]
• Lower IQ
• Learning disabilities, seen in subjects such as language comprehension and mathematics
• Substance abuse
• Mental health problems
• Congenital heart defects and other medical conditions
DIAGNOSIS
HISTORY
• Exposure to alcohol in utero
• NOTE: Patients often underreport consumption due to stigmatization.
PHYSICAL EXAM
• Ophthalmological findings are frequently seen in children with FAS, the most common findings are (7)[A] the following:
– short palpebral fissures, ptosis, epicanthus, telecanthus
– microphthalmos
– strabismus (especially esotropia)
– reduced acuity, unilaterally, or bilaterally
– refractive error, most often myopia
– anterior segment and media opacities,
– retinal dysplasia, tortuous retinal vessels
– optic nerve hypoplasia
– cortical visual impairment in severe cases
• Also look for the nonophthalmologic/facial anomalies including head circumference
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• No reliable biochemical markers available
• Markers proposed for identifying drinking in pregnant women include fatty acid ethyl ester levels in meconium and hair samples, gamma-glutamyl transferase (GGT), hemoglobin-associated acetaldehyde, and carbohydrate-deficit transferrin. However, none has been proven to have high sensitivity and specificity (3)[C].
Imaging
CT/MRI of brain to detect associated anomalies.
Diagnostic Procedures/Other
Electroretinogram results have been inconsistent, further research necessary before considering using ERG to diagnose FAS (7)[C].
DIFFERENTIAL DIAGNOSIS
• Many infants born with congenital syndromes and malformations have characteristics that resemble ophthalmologic features seen in children with FAS and they have coincidentally been exposed to alcohol in-utero (1)[A]
• Velocardiofacial syndrome (VCFS).
• Williams syndrome
• Blepharophimosis syndrome
• Dubowitz syndrome
TREATMENT
MEDICATION
• None for ophthalmologic abnormalities
• Stimulant medications such as methylphenidate and dextroamphetamine have some efficacy in treating children with concomitant psychiatric problems (e.g., ADHD), but larger-scale studies are needed to confirm this (6)[A].
ADDITIONAL TREATMENT
General Measures
• In children with amblyopia, patching of the better eye should be attempted
• Treat refractive errors with corrective lens
Issues for Referral
If there are characteristics inconsistent with the diagnosis, consider referral to a clinical geneticist or dysmorphologist.
Additional Therapies
• Medical services for any comorbid conditions
• For associated ocular conditions as needed (6)[A]
SURGERY/OTHER PROCEDURES
For associated strabismus or ptosis as indicated.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• As needed for amblyopia detection and treatment
• Low vision services as indicated
PATIENT EDUCATION
• Parents of should be educated on the nature of FAS, e.g., to recognize behavioral issues as a manifestation of the syndrome and learn to cope with their children’s symptoms caused by FAS (6).
• http://www.nofas.org/living/resources.aspx
• Mothers who engage in alcohol abuse prenatally are likely to continue after the birth of their child. Appropriate interventions (e.g., Alcoholics Anonymous) should be recommended.
PROGNOSIS
Improvement in vision depends on early identification and intervention, in infancy or preschool age.
COMPLICATIONS
Irreversible loss in visual acuity if amblyopia from strabismus or refractive error not corrected
REFERENCES
1. Hoyme HE, May PA, Kalberg WO, et al. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 Institue of medicine criteria. Pediatrics 2005;115(1):39–47.
2. Strömland K. Visual impairment and ocular abnormalities in children with fetal alcohol syndrome. Addict Biol 2004;9(2):153–157; discussion 159–160.
3. Green RF, Stoler JM. Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview. Am J Obstet Gynecol 2007;197(1):12–25.
4. Sokol RJ, Delaney-Black V, Nordstrom B. Fetal Alcohol Spectrum Disorder. JAMA 2003;290(22):2996–2999.
5. Floyd RL, Weber MK, Denny C, O’Connor MJ. Prevention of fetal alcohol spectrum disorders. Dev Disabil Res Rev 2009;15(3):193–199.
6. Strömland K, Pinazo-Durán MD. Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol Alcohol 2002;37(1):2–8.
7. Paley B, O’Connor MJ. Intervention for individuals with fetal alcohol spectrum disorders: treatment approaches and case management. Dev Disabil Res Rev 2009;15(3):258–267.
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