3 -  Fetal alcohol syndrome and autism
     Nanson (1992) described in careful detail the
difference between the fetal alcohol behavioral
phenotype from that of infantile autism [1].  However,
in a clinic database of 326 individuals with alcohol-
related birth defects, she discovered six cases of
children with the physical phenotype of fetal alcohol
syndrome (FAS) but who displayed autistic behaviors
rather than behavioral characteristics usually
associated with fetal alcohol syndrome.

    The FAS children with autism were more severely
affected than were the non-autistic FAS children.  
They had greater growth retardation, smaller head
circumference, and were more retarded; they did not
relate well to other people, were resistant to change,
and showed abnormal sensory responses such as
hypersensitivity to noise.  Only two had language, but
were echolalic and reversed pronouns.  The autistic
group also had a greater number of physical
anomalies, and three of the six had cleft lip or palate.  
Nanson noted that cleft lip or palate has been
reported in FAS but that it is uncommon in autism.

    The finding of autism among children with FAS can
be compared to cases of autism associated with
phenylketonuria, tuberous sclerosis, or cerebral
lipidosis.  It represents involvement of the brain area
responsible for the core syndrome of autism, but as
part of a more widespread disorder, and this brain
area is apparently only affected in the most severe
cases of fetal alcohol syndrome.  The focus of
research on autism should be to locate the area of the
brain that leads to the core syndrome.

    Nanson (1992) pointed out that no single
etiological factor or combination of factors has been
found responsible for autism.  On the contrary, autism
is a syndrome with many different etiologies and
prenatal exposure to alcohol is just one more.  
Exposure in utero to alcohol, toxic metabolites in
genetic disorders like phenylketonuria, rubella virus
infection, or hypoxic injury all affect areas of the brain
that also include the site or sites responsible for
autism.  The high vulnerability of the auditory system
should make this a logical starting point in the search
for the brain area that is impaired in children with
autism.

    Harris et al. (1995) added three more cases to
those reported by Nanson [2].  These three children
also all had been exposed prenatally to cocaine.  One
mother had additionally used marijuana, another
hashish, and the third heroin plus diazepam (Valium),
triazolam (Halcion), and lorazapam (Ativan).  Harris et
al. suggested the need for prospective studies to
investigate the comorbidity of alcohol-related birth
defects and autism.

    Aronson et al. (1997) provided a prospective follow-
up on 22 children born to alcoholic mothers [3].  Two
met the diagnostic criteria for Asperger syndrome and
one the criteria for an autistic-like condition.  Aronson
et al. also cited the inclusion of patients with prenatal
alcohol exposure in two earlier research studies of
autistic children [4].  Prenatal exposure to alcohol is
likely also to have played a role in the neuropathology
of the cases reported by Rodier et al. (1996) and
Guerin et al. (1996) as discussed in the preceding
chapter [5, 6].

    Davis et al. (1992) evaluated 70 children born to
mothers who used cocaine during pregnancy [7].  
Eight children met the criteria for a diagnosis of
autism.  Three of the mothers also had histories of
regular alcohol use.  The mothers of the three children
with fetal alcohol syndrome reported by Harris et al.
(1995) all used cocaine as well as alcohol during
pregnancy.  Three mothers of the children followed by
Church et al. (1997) acknowledged abuse of cocaine
or other illicit drugs [8].  Polydrug use is common
among those who drink to excess, and this behavior
was noted in most of the cases describing autism in
children with fetal alcohol syndrome.

    There are some similarities between the
neuropathology found at autopsy in autism and FAS,
but the damage is more extensive in FAS.  Roebuck et
al. (1998) reviewed both autopsy and magnetic
resonance imaging (MRI) in FAS [9].  Microcephaly,
small brain and cranium, is common in FAS in contrast
to autism which is often associated with a normal-sized
or large brain.  Evidence of abnormal cell migration is
evident in FAS, but is more pronounced than in
autism.  Brain malformation in FAS can be compared
to craniofacial anomalies such as cleft palate.  Often
there is agenesis or hypoplasia of midline structures
such as the corpus callosum or cerebellar vermis.  
Brainstem and cerebellar defects are common in FAS.  
MRI studies include less seriously affected children
than those whose brains have been studied at
autopsy.  Nevertheless, hypoplasia of the corpus
callosum, basal ganglia, and cerebellar vermis has
been seen on MRI scans.

    Maternal use of alcohol and drugs during
pregnancy is important to seek out in cases of autism,
but cannot be expected to be easy.  Rodier et al.
(1996, 1997b) mentioned that the mother of the
autistic patient they followed had several hospital
admissions for addiction to alcohol and other drugs
after the birth of her autistic child [5, 10].  Before her
daughter’s autism can be viewed as idiopathic and the
abnormalities found in her brainstem as representative
of pathology underlying the core syndrome of autism,
prenatal exposure to alcohol needs to be definitely
ruled out.
  1. Nanson JL (1992) Autism in
    fetal alcohol syndrome: a
    report of six cases.
  2. Harris SR et al. (1995)
    Autistic behaviors in offspring
    of mothers abusing alcohol
    and other drugs: a series of
    case reports.
  3. Aronson M et al. (1997)
    Attention deficits and autistic
    spectrum problems in
    children exposed to alcohol
    during gestation: a follow-up
    study.
  4. Hauser SL et al. (1975)
    Pneumographic findings in
    the infantile autism
    syndrome. A correlation with
    temporal lobe disease.
  5. Rodier PM et al. (1996)
    Embryological origin for
    autism: developmental
    anomalies of the cranial
    nerve motor nuclei.
  6. Guerin P et al. (1996)
    Neuropathological study of a
    case of autistic syndrome
    with severe mental
    retardation.
  7. Davis E et al. (1992) Autism
    and developmental
    abnormalities in children
    with perinatal cocaine
    exposure.
  8. Church MW et al. (1997)
    Hearing, language, speech,
    vestibular, and dentofacial
    disorders in fetal alcohol
    syndrome.
  9. Roebuck TM et al. (1998) A
    review of the
    neuroanatomical findings in
    children with fetal alcohol
    syndrome or prenatal
    exposure to alcohol.
  10. Rodier PM et al. (1997b)
    Linking etiologies in humans
    and animal models:  Studies
    of autism.
Full References
top
References
  1. Nanson JL (1992) Autism in fetal alcohol syndrome: a report of six cases. Alcoholism,
    Clinical and Experimental Research 16:558-565.
  2. Harris SR, MacKay LL, Osborn JA (1995) Autistic behaviors in offspring of mothers
    abusing alcohol and other drugs: a series of case reports. Alcoholism, Clinical and
    Experimental Research 19:660-5
  3. Aronson M, Hagberg B, Gillberg C (1997) Attention deficits and autistic spectrum
    problems in children exposed to alcohol during gestation: a follow-up study.
    Developmental Medicine and Child Neurology 39:583-7
  4. Hauser SL, DeLong GR, Rosman NP (1975) Pneumographic findings in the infantile
    autism syndrome. A correlation with temporal lobe disease. Brain 98:667-88
  5. Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J (1996) Embryological origin for
    autism: developmental anomalies of the cranial nerve motor nuclei. Journal of
    Comparative Neurology 370:247-261.
  6. Guerin P, Lyon G, Barthelemy C, Sostak E, Chevrollier V, Garreau B, Lelord G (1996)
    Neuropathological study of a case of autistic syndrome with severe mental retardation.
    Developmental Medicine and Child Neurology 38:203-211.
  7. Davis E, Fennoy I, Laraque D, Kanem N, Brown G, Mitchell J (1992) Autism and
    developmental abnormalities in children with perinatal cocaine exposure. Journal of the
    National Medical Association 84: 315-319.
  8. Church MW, Eldis F, Blakley BW, Bawle EV (1997) Hearing, language, speech,
    vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcoholism, Clinical and
    Experimental Research 21:227-237.
  9. Roebuck TM, Mattson SN, Riley EP (1998) A review of the neuroanatomical findings in
    children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcoholism,
    Clinical and Experimental Research 22:339-44.
  10. Rodier PM, Ingram JL, Tisdale B, Croog, V.J. (1997b) Linking etiologies in humans and
    animal models:  Studies of autism.  Reproductive Toxicology 11:417-422.