Fetal Alcohol Syndrome: An Ophthalmologic Perspective
Fetal Alcohol Syndrome (FAS) is an irreversible congenital condition that is a result of maternal alcohol use during pregnancy. Classic signs include: abnormal facial features (short horizontal palpebral fissure/blepharophimosis, thin vermillion border, and smooth philtrum), growth retardation, and neurobehavioral impairment. These signs range greatly in severity, and can include any combination of the classic signs.
FAS is a syndrome that falls under a larger group of conditions known as Fetal Alcohol Spectrum Disorder (FASD). FASD includes:
- Alcohol-Related Neurodevelopmental Disorder (ARND): may have intellectual disabilities and problems with behavior and learning.
- Alcohol-Related Birth Defects (ARBD): may have problems with the heart, kidney, bones, or hearing.
- Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): mother must have consumed more than minimal levels of alcohol before the child’s birth AND the child will have problems in 3 areas: 1) thinking and memory, 2) behavior, mood, and shifting attention between tasks, and 3) trouble with day-to-day living and playing with others.
- FAS: the most severe end of the spectrum involving central nervous system (CNS) problems, facial features, and growth problems.
Alcohol is a known CNS teratogen that causes reduced brain volume and irregular brain and facial structure. Alcohol crosses the placenta and, although there are many hypotheses, the exact mechanism by which alcohol induces CNS and structural changes is still unclear. Some proposed mechanisms include: direct cytotoxic effect to embryonic cells (specifically the anterior neural ridge which organizes the prosencephalon), epigenetic changes leading to disrupted neural plasticity, and disruption of retinoic acid-based cell signaling.
The Centers for Disease Control and Prevention (CDC) studies show FAS occurring in 0.2 to 1.5 infants for every 1,000 live births in certain areas of the US, with the most recent study finding FAS in 0.3 out of every 1,000 children from 7-9 years old. More recent studies have shown FAS to have a prevalence as high as 98.5 per 1,000 in certain US populations. The estimated lifetime cost on average for an individual with FAS in 2002 was 2 million US dollars.
Ocular Specific Pathology
- Blepharophimosis (short horizontal palpebral fissures, i.e. decreased distance between the medial and lateral canthi) is commonly found and easy to measure.
- Blepharoptosis (drooping of upper eyelid) is non-specific, but can be seen in some FAS patients.
- Epicanthus or epicanthal folds (vertical fold of skin on the lateral nose, figure 1), a finding reported in up to 80% of infants exposed to alcohol having epicanthus.
- Microphthalmia (abnormal and small eyes, figure 2) is commonly found in FAS and can aid in diagnosis of FAS.
- Telecanthus (increased distance between the medial eye canthi) is commonly found in FAS.
- Increased tortuosity of the retinal vessels, found in up to 49% of Swedish children with FAS.
- Optic nerve hypoplasia (in experimental models, this is due to reduced densities of ganglion cells and their axons along with damage to glial cells and myelin sheaths) or optic atrophy, found in up to 48% of Swedish children with FAS.
- Cornea and anterior chamber: findings resembling Axenfeld-Rieger syndrome and Peter's anomaly, glaucoma, uveal coloboma.
- Lens: cataract.
- Persistent fetal vasculature.
- Dysmorphogenesis of the retina.
Eye Movement and Eye Function (motor control and executive function)
- Strabismus (abnormal alignment of eyes, figure 3) is non-specific, but commonly found in FAS.
- Prolonged reaction times, excessive direction errors, and no expression of saccades.
- Decreased vision in up to 65% of Swedish children with FAS with acuity < 0.2 (20/32 Snellen equivalent).
- Possible dysfunction of frontal lobes
Early detection and diagnosis leads to significantly less comorbidities and symptoms in later life of FAS patients. FAS is diagnosed clinically and requires at least 2 of the following findings:
- characteristic facial features (short horizontal palpebral fissure
- thin vermillion border, smooth philtrum)
- signs of growth retardation (height and/or weight <10th percentile)
- clear evidence of brain involvement
- neurobehavioral involvement
Documented maternal alcohol use is not necessary but can help support a diagnosis FAS if present. FAS is often missed in newborns and can have a diagnostic delay as late as early adulthood. Facial features characteristic of FAS typically diminish with age, which reduces the chance of detecting classic dysmorphology in adult evaluations. While there are ongoing efforts in search of more sensitive biomarkers to aide in the diagnosis of FAS, diagnosis remains clinical and relies on a multidisciplinary approach.
Ocular Signs and Symptoms
The only ophthalmologic diagnostic criteria for FAS is short palpebral fissures, but there are many periocular and intraocular signs that can point to a diagnosis of FAS. See above: Ocular Specific Pathology.
Ocular signs present earlier than signs of growth retardation and brain and neurobehavioral involvement and thus can be useful in aiding the early diagnosis of FAS. Ophthalmologic abnormalities such as refractive errors, strabismus, and fundus abnormalities seem to remain unchanged and persistent throughout childhood and adolescence.
Detection through ophthalmologic exam
With the rising prevalence of FAS, there is an opportunity for the field of ophthalmology to drastically reduce the morbidity of FAS patients through potentially earlier diagnosis and management with a thorough eye exams. Some studies suggest a full ophthalmic exam in all children who are suspected of having FAS. This exam includes: inspection of periocular features (supplemented with morphometric analysis if needed), visual acuity (with visual evoked potentials if needed), slit lamp exam, and ophthalmoscopic exam with particular attention to the optic disc for signs of hypoplasia and the retina vasculature for signs of tortuosity. Visual acuity can also be used to aid in diagnosis as children with FAS tend to have reduced best-corrected visual acuity. Eye movement tasks and eye tracking measures are other potential tools for assessing FAS in children as well as measuring executive function in FAS patients. Providing an FAS diagnosis earlier in life through an eye exam could help provide earlier management of this disease overall and reduce both ocular comorbidities (vision loss) and cognitive/neurobehavioral comorbidities.
A 2016 meta-analysis showed that the five most prevalent comorbidities of FAS were: expressive language disorder, chronic otitis media, conduct disorder, receptive language disorder, and abnormal function of peripheral nervous system and special senses. There also tend to be higher rates of mental disorders in people with FAS and those with FAS are at higher risk of violent behavior, criminality, and criminalization than the average population.
Syndromes that may appear similar to FAS include: Williams Syndrome, DiGeorge Syndrome, Velocardiofacial Syndrome, Noonan Syndrome, Fetal Hydantoin Syndrome, Fetal Valproate, Dubowitz syndrome, fetal toluene embryopathy and Maternal Phenylketonuria (PKU).
FAS is an irreversible congenital disorder that can only be prevented by decreasing alcohol intake during the whole pregnancy. Though research exploring ways to mitigate the effects of alcohol on a developing fetus suggests that antioxidants present in cruciferous vegetables like broccoli may help reduce the stress of alcohol on neural crest cells. There is no known safe limit of alcohol consumption during pregnancy. Both quantity and pattern (binge) of drinking are more likely important factors in the teratogenic effects. Pregnant women and reproductive-aged women without reliable contraception should be advised to abstain from alcohol.
Early detection along with appropriate behavioral and special education are the most important factors for improved outcomes in children with FAS. These specialized therapies improve social and cognitive abilities and have an inverse relationship with time of diagnosis. Treatment is highly individualized and can include occupational therapy, speech therapy, and cognitive behavioral therapy for patients who suffer from anxiety and/or depression.
There are no specific medications approved to treat FAS, but appropriate medication can be used for related disease manifestations (e.g. stimulants for hyperactivity).
FAS is a lifelong disorder, and most treatment is addressed at the level that the syndrome is expressed. Patients generally tend to have lower academic performance, difficulty reading social cues, and higher rates of incarceration. These manifestations of FAS can lead to downstream effects on health through socioeconomic factors.
Long-term prognosis for FAS patients is generally poor with higher rates of alcohol/drug abuse, psychiatric disorders, unemployment, sexual misconduct, and disability. Studies suggest there may be an association between FAS and Autism Spectrum Disorder. One study also reported much lower average life expectancy for FAS patients at 34 years old with deaths reported due to suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%), diseases of the nervous and respiratory systems (8% each), and diseases of the digestive system (7%).
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- National Organization on Fetal Alcohol Syndrome: https://nofas.org/
- Families Affected by Fetal Alcohol Spectrum Disorder (FAFASD): https://fafasd.net/
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