SSBP Syndrome Information Sheet
Foetal alcohol syndrome
Alcohol related neurodevelopmental disorder

Original description:
First observed in Nantes by paediatrician Paul Lemoine in 1968 who described similar dysmorphic facial features and growth delays in 127 infants of pregnant alcohol-drinking mothers. Fetal Alcohol Syndrome (FAS) was coined in Seattle by David Smith and Ken Jones in 1973(1,2).The Institute of Medicine in 1996 delineated Full FAS, Partial FAS, and Alcohol Related Neurodevelopmental Disorder (ARND) based on the presence or absence of facial dysmorphology and /or growth retardation (3). ARND replaced the old term Fetal Alcohol Effect (FAE). FAS Spectrum Disorders, an umbrella term, was introduced by O’Malley & Hagerman in 1998, refined to Fetal Alcohol Spectrum Disorders (FASD) by Streissguth & 0’Malley in 2000 (4,5).

Incidence:
Incidence for FAS alone varies from 3 per 1,000 live births in the USA to 40 per 1,000 births in South Africa. Incidence of FAS and ARND together was 9.1 per 1000 live births in Seattle (6,10, 13). Genetic differences in the susceptibility to alcohol based on the mother’s liver metabolism and/ or higher maternal alcoholism effect varying incidence rates (7).

Life Expectancy:
No documentation of decreased life expectancy.

Physical Phenotype:
Characteristic facial features include short palpebral fissures, thin (flat) upper lip, flattened philtrum, flat midface Growth retardation less than the 10th percentile for height and weight. Low birth weight for gestational age, decelerating weight over time not due to nutrition, disproportional low weight –to-height ratio. FAS has the classic facial features, ARND does not have the facial features. Gross and fine motor delays as in Developmental Coordination Disorder. Alcohol Related Birth Defects (ARBD) with eye, renal, cardiac and/or skeletal anomalies. FAS is the much less common form of FASD (3, 8, 9, and 10).

Psychiatric/Behavioral Disorders:
Infants can demonstrate Primary Regulatory Disorders characterized by difficulties in tolerating environmental stimuli (i.e. habituation problems), co-ordinating basic motor movements (i.e. sucking), or interacting with parents or care-providers. Secondary psychiatric disorders appear due to environmental stressors such as PTSD after physical or sexual abuse, or Reactive Attachment Disorder of Infancy or Early Childhood related to separation from birth mother or multiple foster home placements. FASD ‘masquerade’ in the form of many common psychiatric disorders, such as ADHD, Mood Disorder, Anxiety Disorder, Alcohol or Drug Dependence, PDD and Schizoaffective Disorder. Personality Disorders seen are, Avoidant, Dependent, Schizoid, Passive/Aggressive and Borderline. Presence or absence of facial dysmorphology or growth features do not clinically correlate with the psychiatric presentation or structural brain damage in FASD (5,8, 11, and 12).

Neuropsychological Deficits:
70- 75% of patients with FASD are not mentally retarded. The neuropsychological profile consistently shows a Complex Verbal and Non-Verbal Learning Disorder affecting multiple domains of functioning including attention, impulsivity, working memory, executive function, social skills, interpersonal relatedness and language development. It includes a Mathematics Disorder and/ or Disorder of Written Expression and/or Reading Disorder, and. evidence of a Mixed Receptive/ Expressive Language Disorder with specific deficits in social cognition and social communication. Vineland Adaptive Behavioral Scale (VABS) shows Functional Deficits in daily living skills, socialization and communication (3, 5, 8,9,10 and 13).

Brain Structural Abnormalities:
Autopsy reports of infant deaths showed diffuse structural brain changes including hydrocephalus, microcephaly, corpus callosal agenesis, cerebellar hypoplasia, enlarged ventricles and hetertopias (8, 9). Brain imaging studies consistently show microcephaly. The corpus callosum is most commonly affected. The basal ganglion caudate and the hippocampus, integral in working memory and executive function, may be decreased in shape and volume, and the cerebellum may be smaller (5,9,14).

Brain Neurotransmitter and Neurophysiological Abnormalities:
Diffuse CNS neurotoxic effects include cell death and/or disruption of cell migration, proliferation, differentiation and maturation (3,5, 8, and 9).Deficits discovered in all neurotransmitter systems. Dopaminergic and noradrenergic deficits likely connected to ADHD presentation of FASD (4,12,15).EEG abnormalities in infant/ child cerebral immaturity, sleep state EEG, as well as temporal lobe dysrhythmia and complex partial seizure disorder in 6 to 19 year olds with FASD (1,12).

REFERENCES
1. Lemoine P, Harousseau H & Borteyru JP (1968) Les enfants de parents alcoholiques: Anomalies observees a propos de 127 cas. Quest Med, 21, 476- 482.
2. Jones KL & Smith DW (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet, 2, 999-1101.
3. Stratton KR, Rowe CJ & Battaglia FC (1996) Fetal Alcohol Syndrome: Diagnosis, epidemiology, prevention and treatment in medicine. National Academy Press, Washington DC.
4. O’Malley KD, Hagerman R.J (1998) Developing Clinical Practice Guidelines for Pharmacological Interventions with Alcohol-affected Children. Proceedings of a special focus session of the Interagency Co-ordinating Committee on Fetal Alcohol Syndrome. Chevy Chase Ma, Sept 10TH & 11th, CDC & NIAAA (Eds.), 145-177
5. Streissguth AP & O’Malley KD (2000) Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Seminars in Clinical Neuropsychiatry, 5, 177-190.
6.Sampson, PD, Streissguth AP, Bookstein FL, Little RE, Clarren SK, Dehaene P, Hanson Jr. JW (1997) Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology, 56 (6): 317-326.
7. Mc Carver, DG, Thomasson, HR, Martier, SS, Sokol, RJ, Li, TK (1997) Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African Americans. J.Pharmacol Exp Ther: 283(3), 1095-1101
8. Streissguth AP (1997) Fetal alcohol syndrome. A guide for families and communities. Brookes Publishing, Baltimore.
9. Hagerman RJ (1999) Neurodevelopmental Disorders. Diagnosis and Treatment. Fetal Alcohol Syndrome, 3-59, Oxford University Press, New York, New York, Oxford.
10. Chudley, AE, Conroy, J, Cook, JL, Loock, C, Rosales, T, LeBlanc, N (2005) Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ: 172(5 suppl)):S1-21
11. Famy, C, Streissguth, AP, Unis, AS (1998) Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Am J. Psychiatry: 155:4, 552-554
12. O’Malley KD & Storoz L (2003) Fetal alcohol spectrum disorder and ADHD: diagnostic implications and therapeutic consequences. Expert Review of Neurotherapeutics, July, Vol. 3. No. 4, 477-489.
13.Streissguth, AP, Bookstein, FL, Barr, HM, Sampson, PD, O’Malley KD,
Kogan Young (2004) Risk factors for adverse risk outcomes in fetal alcohol syndrome and fetal alcohol effects. Developmental and Behavioral Pediatrics, Vol. 25.No. 4, 228-38
14. Bookstein, FL, Sampson, PD, Streissguth, AP, Connor, PL (2001) Geometric morphometrics of corpus callosum and subcortical structures in fetal alcohol affected brain. Teratology, 64, 4-32
15. Sobrain, SK, Jones, BL, James, H, Kamara, FN, Holson, RR (2005) Prenatal alcohol preferentially enhances reactivity of the dopamine D1 but not D2 or D3 receptors in offspring. Neuorotoxicology and Teratology, 27, 73-93

Kieran D.O’Malley, July 2005