Research in Autism Spectrum Disorders 3 (2009) 829–839

Contents lists available at ScienceDirect

Research in Autism Spectrum

Disorders
Journal homepage: http://ees.elsevier.com/RASD/default.asp

Review

Autism spectrum disorders in Down syndrome: A review

Colin Reilly a,b,*,1
a
Psychology Department, St. Michael’s House Service for Children and Adults with Intellectual Disability, Ballymun Road,
Dublin 9, Ireland
b
School of Education, University College Dublin, Belfield, Dublin 4, Ireland

A R T I C L E I N F O A B S T R A C T

Article history: While it had been claimed that the association of autism spectrum
Received 27 December 2008 disorders (ASDs) and Down syndrome was uncommon there are
Accepted 2 January 2009 now a substantial number of studies demonstrating that a subgroup
of those with Down syndrome will also reach the diagnostic criteria
Keywords: for an ASD. This review examines published research on the
Autism spectrum disorders prevalence of ASDs in Down syndrome. The manifestation of ASDs
Down syndrome in the Down syndrome population is also examined with regard to
Prevalence
published case studies and profiles on ASD screening and diagnostic
Manifestation of symptoms
instruments. Possible correlates of ASDs in Down syndrome
Medical factors
Cognitive functioning including level of cognitive functioning, medical factors, gender,
Gender and family history are also reviewed. Issues regarding the
Family history diagnostic assessment of ASDs in Down syndrome and suggestions
Diagnostic issues for future research are discussed.
ß 2009 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 830
2. Why diagnose ASDs in those with Down syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 830
3. Prevalence of ASDs in the Down syndrome population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
4. Manifestation of ASDs in Down syndrome: standardised instruments . . . . . . . . . . . . . . . . . . . . . . . 832
5. Manifestation of ASDs in Down syndrome: case reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833
6. Medical factors associated with a diagnosis of an ASD in an individual with Down syndrome . . . . . 835
7. Cognitive functioning in individuals with Down syndrome and ASDs . . . . . . . . . . . . . . . . . . . . . . . 835
8. Gender ratio of individuals with Down syndrome and an ASD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 835

* Corresponding author. Tel.: +353 876220119.

E-mail address: colinreilly@ireland.com (C. Reilly).
1
Tel.: +353 1 8840294.

1750-9467/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rasd.2009.01.012
830 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839

9. Family history of individuals with Down syndrome and ASDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 836

10. Diagnosing ASDs in children/adults with Down syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 836
11. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838

1. Introduction

While some disorders have a well established association with autism spectrum disorders (ASDs),
such as fragile X syndrome (Bailey et al., 1999) and tuberous sclerosis (Gillberg, Gillberg, & Ahlsen,
1994; Hunt & Shepard, 1993), it has been claimed that the association of ASDs and Down syndrome is
uncommon (Rutter & Schopler, 1988). The typical personality profile of Down syndrome (i.e., that of an
individual who is affectionate and outgoing) goes against the behavioral phenotype of ASDs
(Ghaziuddin, Tsai, & Ghaziuddin, 1992; Howlin, Wing, & Gould, 1995). While people with Down
syndrome have been traditionally described as friendly, affectionate, and extroverted (Gibbs & Thorpe,
1983), there is evidence that not all individuals with Down syndrome possess these personality
characteristics. Some 10–20% of persons with Down syndrome display significant behavioral
problems (Flynt & Yule, 1994; Gibson, 1978). It is possible that the 10–20% of persons with Down
syndrome manifesting behavioral difficulties contain a substantial number of individuals with co-
morbid ASDs, although the exact prevalence rate of ASDs in individuals with Down syndrome has been
difficult to ascertain (Ghaziuddin et al., 1992; Howlin et al., 1995). However, it is apparent that
individuals with Down syndrome and an ASD, have been under-reported and inadequately studied
with regard to their neurobehavioral phenotype, and how it compares to either ‘typical’ Down
syndrome individuals or individuals with ASDs without Down syndrome (Capone, Grados, Kaufmann,
Bernad-Ripoll, & Jewell, 2005).

2. Why diagnose ASDs in those with Down syndrome?

The early identification of ASDs may increase the success rate of interventions (Greenspan,
1992; Lovaas, 1987), and may also allow time for genetic counselling and to initiate parental
support (Baird et al., 2001). Over the last decade, it has been increasingly demonstrated that the
diagnosis of Autistic Disorder can be made accurately in children as young as 2 years (Cox et al.,
1999; Lord, 1995; Stone et al., 1999), though there is more variability with children with early
diagnoses of Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) (Charman &
Baird, 2002). However, children with Down syndrome and ASDs are not likely to be recognised as
early as children with ASDs alone, and as children with Down syndrome and an ASD tend to be
diagnosed later than children with an ASD alone, opportunities for intensive early intervention
may be lost. The early identification of ASDs is not without challenges and these challenges may be
accentuated in relation to identification in the Down syndrome population. Some of the behaviors
specified by the DSM-IV-TR (American Psychiatric Association (APA), 2000) for the diagnosis of
ASDs in older children, may not be present in young children with ASDs or children with
developmental delays, such as those with Down syndrome, because they have not developed the
prerequisite skills to exhibit the behaviors (Stone et al., 1999), and this has lead to calls for more
developmentally sensitive criteria (Chawarska & Volkmar, 2005). Young children with Down
syndrome and ASDs will share features with children with Down syndrome alone, and
differentiating children with Down syndrome and ASDs, from Down syndrome alone, may be
difficult especially in younger children. Professionals may believe that the behaviors and language
delays in children with Down syndrome and ASDs are related to the cognitive delays they associate
with Down syndrome, as opposed to the presence of an ASD.
The clinical and educational implications of missing a diagnosis of an ASD are significant (Kent,
Perry, & Evans, 1998). Late diagnosis, or indeed the failure to diagnose at all, may have detrimental
effects on the lives of the affected children and their families. A failure to recognise or diagnose ASDs in
children with Down syndrome may result in inappropriate educational placement for these children
 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839 831

and unnecessary emotional hardship for their parents (Ghaziuddin et al., 1992; Howlin et al., 1995),
and prevent parents from accessing supports and interventions available to families with children
who have a diagnosed ASD (Filipek, 2005). Appropriate provision for children with a dual diagnosis is
likely to be different from that for individuals with Down syndrome who do not have an ASD, and this
may have implications for educational and residential services (Kent et al., 1998). Earlier identification
of ASDs in those with Down syndrome may ensure provision of appropriate advice and education
(Kent, Evans, Moli, & Sharp, 1999). Having access to services for those with ASDs, and to professionals
experienced in the management of ASDs, is likely to be of significant benefit to those affected by both
Down syndrome and an ASD.

3. Prevalence of ASDs in the Down syndrome population

While a number of studies have attempted to ascertain the prevalence of ASDs in children with
Down syndrome, prevalence figures have been influenced by the sample size, age range of sample, and
the instruments, informants, and diagnostic criteria employed (Kent et al., 1998). Many of the studies
have not employed ‘gold standard’ diagnostic instruments and are based on outdated diagnostic
criteria. Wing and Gould (1979) carried out an epidemiological study of 35,000 children under the age
of 15 years, using the Medical Research Council’s Handicaps, Behavior, and Skills interview schedule
(HBS; Wing & Gould, 1978). They reported one child from a total of 30 fully ambulant children with
Down syndrome who met two essential criteria for ‘Kanner’s autism’ (Kanner & Eisenberg, 1956).
Another two children were classified as on the autism spectrum but were not classified as having
Kanner’s autism. In a study of psychiatric disorders in children with mild and severe mental
retardation by Gillberg, Persson, Grufmann, and Themner (1986) one child with Down syndrome met
DSM-III (APA, 1980) criteria for autism. Lund (1988) used the revised Medical Research Council’s
Schedule of Handicaps, Behavior, and Skills (HBS; Wing, 1980) and reported that five out of 44 (11%)
individuals with Down Syndrome had the symptoms of ‘infantile autism’ described as comprising
autistic contact, severe language impairment, and stereotyped behavior. Turk (1992) also using the
HBS schedule, reported that 9% of his series of children with Down syndrome met the full ICD-10
criteria for autism (World Health Organization (WHO), 1992). Ghaziuddin et al. (1992) found two
children who fulfilled DSM-III-R criteria for ‘Autism’ (APA, 1987) from an estimated total of 40
children with Down syndrome.
One of the most comprehensive studies carried out into the prevalence of ASDs in the Down
syndrome population was that of Kent et al. (1998) who identified four children with both Down
syndrome and an ASD, out of 33 children with Down syndrome within a geographical area of the West
Midlands in the UK. It was estimated that there were 58 children with Down syndrome in the region,
but only 33 children went through the full research protocol. The children studied were aged between
two and 16 years. The parents of the 33 children completed the Asperger’s Syndrome Screening
Questionnaire (ASSQ) (Ehlers & Gillberg, 1993), which is a 27-item screening questionnaire designed
for use by parents and teachers to screen for social deficits associated with ASDs among high
functioning children on the autism spectrum and is not ideal for screening children with mental
retardation. Each parent was interviewed at home and the Childhood Autism Rating Scale (CARS)
(Schopler, Reichler, & Renner, 1986) was completed at interview. Each child was diagnosed according
to the ICD-10 (WHO, 1992) criteria for ASDs and level of mental retardation. Of the 33 children
assessed, four (12%) had difficulties which placed them on the autism spectrum according to the ICD-
10 criteria, and of these four children, one child met criteria for ‘childhood autism’.
A Brazilian study involved screening 180 individuals with Down syndrome using the Autism
Screening Questionnaire (ASQ; Berument, Rutter, Lord, Pickles, & Bayley, 1999) (Lowenthal, Paula,
Schwartzman, Brunioni, & Mercadante, 2007). Of the 180 screened, 10 individuals (5.5%) met the cut-
off for Autistic Disorder and 18 individuals (10%) met the criteria for Pervasive Developmental
Disorder-Not Otherwise Specified (PDD-NOS). In total, 28 individuals (15.6%) met the cut-off for an
ASD on the ASQ. Hepburn, Philofsky, Fidler, and Rogers (2008) undertook comprehensive evaluations
of 20 two-year old children with Down syndrome using the Autism Diagnostic Observation Schedule-
Generic (ADOS-G; Lord, Rutter, DiLavore, & Risi, 1999) and the Autism Diagnostic Interview-Revised
(ADI-R; Lord, Rutter, & LeCouteur, 1994). For each participant, an experienced clinical psychologist
832 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839

with expertise in ASDs observed and interacted with the child and reviewed the child’s records,
including a review of all the data collected within a research battery. Based upon this comprehensive
assessment, the psychologist made a clinical diagnosis using DSM-IV-TR criteria (APA, 2000). On the
ADOS-G one child exceeded ‘autism’ cut-off on both the social and communication domains of this
instrument. Two children exceeded ‘autism spectrum’ cut-off on both the social and communication
domains. On the ADI-R none of the toddlers with Down syndrome met the ADI-R cut-off for ‘autism’.
However, the three children who had met either ‘autism’ or ‘autistic spectrum’ criteria on the social or
communication domains of the ADOS-G met the criteria for ‘autism’ on the communication scale of
the ADI-R. The psychologists on the team who undertook the comprehensive evaluations determined
that two children (10%) presented with co-morbid Autistic Disorder. The third child, who had met
‘autism spectrum’ criteria on the ADOS-G and ‘autism’ criteria on the communication domain of the
ADI-R, was not classified as having a clinical diagnosis of Autistic Disorder but was on the autism
spectrum. Two years later the same three children who met criteria for an ASD on the ADOS-G and met
criteria for ‘autism’ on the communication domain of the ADI-R at age two also met criteria at age four.
A number of studies of large Down syndrome populations have been conducted which resulted in low
prevalence rates of ASDs. However, most of these studies were done by researchers looking for
occurrences of psychiatric disorders in children and adults with mental retardation and these
researchers were not specifically screening for ASDs. Gath and Gumley (1986) found that 1% of 193
individuals with Down syndrome had autism. In an epidemiological study of autism, Ritvo et al. (1989)
found that of 241 individuals identified with autism, 3 also had Down syndrome. Myers and Pueschel
(1991) found that 1% of 497 individuals with Down syndrome had autism. Collacott, Cooper, and
McGrother (1992) found that 2% of 371 individuals with Down syndrome had autism. Li, Chen, Lai, Hsu,
and Wang (1993) identified Down syndrome in 2 out of 12 children with autism who also had
chromosomal abnormalities from a total of 104 who had an ASD. In a population study in Finland
involving 152,732 children aged under 16 years, 187 children with DSM-IV Autistic Disorder were
identified (Kielinen, Rantala, Timonen, Linna, & Moilanen, 2004), and of these, seven or 3.7% had Down
syndrome. The lower ASD prevalence rates in these studies is unlikely to reflect the true rate of ASDs in
the Down syndrome population. The main issue in these studies was to determine susceptibility of
persons with Down syndrome to psychiatric disorders and not to identify the prevalence of ASDs per se.

4. Manifestation of ASDs in Down syndrome: standardised instruments

Much of the published research on ASDs in Down syndrome has not utilised comprehensive
assessments or ‘gold standard’ diagnostic tools. However, the published research that has utilised
standardised instruments gives an insight into the manifestation of ASDs in Down syndrome. The
study of Kent et al. (1999) found that the ASSQ items which correlated significantly with an eventual
ICD-10 diagnosis of an ASD in their Down syndrome population were; ‘Clumsy, ill-coordinated
movements and gestures’, ‘Compulsory repetitive activities’, and ‘Lives in world of own with restricted
idiosyncratic interests’. In a study by Starr, Berument, Tomlins, Papanikolaou, and Rutter (2005) 13
individuals with Down syndrome with IQs ranging between 24 and 48 were administered the Autism
Diagnostic Interview-Revised (ADI-R; Lord et al., 1994) and the A-PL-ADOS (Berument et al., 2005).
The researchers concluded that five individuals with Down syndrome had an ASD. They noted that the
individuals with Down syndrome who met the diagnostic criteria for an ASD on either instrument, or
both, tended to show more social-emotional responsivity and reciprocity, and a greater range of
emotional facial expression than would be usual in ASDs.
The study of Capone et al. (2005) involved 471 individuals with Down syndrome. Of these, 61 had
an ASD (including 12 with Childhood Disintegrative Disorder (CDD)), 26 had Stereotypic Movement
Disorder (SMD), and the other 384 had Down syndrome alone. Information was gathered on all
participants using the Aberrant Behavior Checklist (ABC; Aman, Singh, Stewart, & Field, 1995). Each of
the ABC subscales was increased in the ASD group compared to the SMD and the Down syndrome
alone groups. The ‘Inappropriate speech’ subscale was the only subscale not significantly lower in the
Down syndrome alone group, when compared to the Down syndrome plus ASD group. The ‘Lethargy’
and ‘Stereotypy’ subscales were significantly higher in the ASD group compared to the SMD group but
neither the ‘Hyperactivity’ nor the ‘Inappropriate speech’ subscale was helpful in distinguishing
 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839 833

between the ASD and SMD groups. Using DSM-IV criteria, children with ASD satisfied an average of
3.5/4 of social impairment criteria, compare to only 1.4/4 for the SMD group. Communication items
were less helpful for distinguishing differences between the ASD and the SMD groups, and the
researchers suggest that this may be because of the poor expressive language skills common in Down
syndrome. Stereotypies were frequent and intense in both the ASD and SMD groups. Children
classified as having an ASD satisfied an average of 3.1/4 of stereotypy behaviour criteria on DSM-IV
compared to 2.5/4 for the SMD group.
In a study involving 127 individuals with Down syndrome, 64 had a co-morbid ASD according to
DSM-IV criteria, 19 had co-existing Stereotypic Movement Disorder (SMD), 18 exhibited co-existing
disruptive behavior disorders, and 26 had no major co-existing psychiatric condition (Carter, Capone,
Gray, Cox, & Kaufmann, 2007). Those with Down syndrome and ASDs included those with Autistic
Disorder, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), and Childhood
Disintegrative Disorder (CDD). When comparing the Down syndrome plus ASD group with the other
groups, the Down syndrome plus ASD group had higher total scores than any other group on both the
Aberrant Behavior Checklist (Aman et al., 1995) and Autism Behavior Checklist (Krug, Arick, & Almond,
1980). The Stereotypy scale of the Aberrant Behavior Checklist was the strongest differentiating factor
between the typical Down syndrome group and the Down syndrome plus ASD group. With respect to
the Autism Behavior Checklist, similar analyses showed that the most discriminating subscale
between the typical Down syndrome and Down syndrome plus ASD groups was the Relating subscale.
Ordered logistic models of Aberrant Behavior Checklist items revealed that item 17 (Odd, bizarre
behavior) of the ABC ‘Stereotypy’ subscale contributed most significantly to the occurrence of ASDs
compared to the typical Down syndrome group. Items 11 (Stereotyped repetitive movements), and 27
(Moves or rolls head back and forth) also differentiated Down syndrome plus ASD from Down
syndrome alone. Item 30 (Isolates self from others) differentiated the Down syndrome plus ASD group
from the Down syndrome with SMD group, with the Down syndrome plus ASD group displaying more
pronounced social withdrawal behavior. The authors of this study concluded that ASDs manifest as a
distinct behavioral phenomenon in Down syndrome and can be differentiated from typical Down
syndrome by anxious behavior, complex and unusual stereotypy, and self-isolation or social
withdrawal (Carter et al., 2007).

5. Manifestation of ASDs in Down syndrome: case reports

Much of the early reports of ASDs in individuals with Down syndrome consisted of case reports.
One of the earliest reports was that by Wakabayashi (1979) who reported a 7-year-old boy with Down
syndrome who also met criteria for autism. The boy showed evidence of physical and motor regression
in the third year of life and appeared to be functioning at a very low level, being dependent on adults
for all his needs. Bregman and Volkmar (1988) described a 12-year-old girl with Down syndrome and
non-verbal abilities in the severely retarded range. She met DSM-III-R (APA, 1987) criteria for Autistic
Disorder and scored within the autistic range on the CARS (Schopler et al., 1986). Although she did not
speak, she had a number of signs and gestures but failed to use these communicatively. Social
interactions were markedly impaired and she exhibited many repetitive behaviors and preoccupa-
tions with the parts and details of objects. She also tended to smell toys and other objects and to feel
them in her mouth.
Ghaziuddin et al. (1992) described three cases with Down syndrome who met DSM-III-R (APA,
1987) criteria for Autistic Disorder and who scored well above the cut-off scores for autism on the
Autism Behavior Checklist (Krug et al., 1980). Two had severe mental retardation and the third had
moderate mental retardation. All three had some speech, although this was repetitive or non-
communicative. Impairments in non-verbal skills, imaginative play, peer relationships, and social
interactions generally, were also noted. The stereotyped and repetitive behaviors they exhibited were
not simply those typically associated with moderate or severe mental retardation as there was also
evidence of the more complex rituals and routines characteristic of ASDs. These included insistence on
repeating the same activities (playing the same records over and over, watching the same television
programme, and lining up and dusting objects), a strong resistance to environmental change, marked
attachment to objects, and a tendency to touch or smell people and objects.
834 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839

Howlin et al. (1995) described four boys aged between 8 and 11 years with Down syndrome and
an ASD. All four had left their initial educational placements due to parental concerns that the schools
were not meeting their children’s needs. It was evident that the four children differed in many ways
from most other children with Down syndrome. Their social relationships were much less well
developed, attachments to adults were delayed, there was little evidence of shared attention, and
empathy, and they failed to use adults for comfort in the usual way. Relationships with other children
were particularly impaired and often characterised by aggression or resistance. Although three of the
children had some speech, their language was abnormal, being echolalic or repetitive, and rarely
used communicatively. For all children their main mode of communication was to take adults by the
hand to indicate their needs. Nonverbal skills such as eye contact and gesture were uniformly poor,
and gesture were uniformly poor, and none of the four showed any spontaneous imaginative play. All
four showed stereotyped motor behaviors and a striking resistance to change and insistence on
routines.
Ghaziuddin (1997) described three cases of Down syndrome with autism who were rated on the
Autism Behavior Checklist. One individual was a 27-year-old with an IQ of 35 who was referred for
evaluation of symptoms of hand-rubbing and facial grimacing. On the Autism Behavior Checklist, he
was given a score of 69 by his mother. Based on the DSM-III-R (APA, 1987), he met criteria consistent
with a diagnosis of Autistic Disorder as shown by the presence of a variety of social and
communicative deficits along with a restricted range of interests dating back from early childhood.
Another individual was a 20-year-old woman with a full-scale IQ of 35. She never pointed her finger to
show interest in her surroundings, nor did she smile socially at others. On the Autism Behavior
Checklist, she scored a total of 61. A diagnosis of Autistic Disorder was made (DSM-III-R; APA, 1987).
The third individual was a 17-year-old male with severe mental retardation. He was referred for
advice about ongoing behavioral problems. His mother had a tendency to engage in excessive routines
and rituals. He scored 89 on the Autism Behavior Checklist. He was given a diagnosis of Autistic
Disorder based on DSM-III-R criteria (APA, 1987).
Kent et al. (1998) described three individuals with Down syndrome and autism. One individual was
a 19-year-old male who was nonverbal. He indicated his needs by taking someone by the hand to what
he wanted. From infancy he avoided eye contact and physical contact with others. He was noted to
prefer his own company, and showed little affection or interest in others. He had always demonstrated
a lack of empathy, did not demonstrate imitative or symbolic play, or differentiate familiar people
from strangers in terms of social interaction. He had a history of pica, unusual attachment to objects,
marked resistance to change, and stereotyped movements. For a number of years previously, he had
demonstrated a repetitive behavior of snatching people’s spectacles from their faces, although this has
largely resolved as a result of a structured behavioral programme. He fulfilled ICD-10 criteria for
Childhood Autism (WHO, 1992). His overall level of functioning was consistent with moderate mental
retardation. The second individual described by Kent et al. (1998) was a 21-year-old male. He did not
babble and only said his first single words at the age of 12. His use of facial expression was limited, and
his only spoken language was a two word phrase. He also showed evidence of depressive disorder
including tearfulness and disturbed sleep patterns. He displayed some delayed echolalia when he was
younger. On examination he displayed impaired eye contact and displayed body rocking. His level of
cognitive ability was assessed a being in the severe range. He was very disturbed by changes in his
routine or by strangers in close proximity, all of which precipitated aggressive outbursts directed
against a person or object. He fulfilled ICD-10 criteria for Childhood Autism. The third individual
described by Kent et al. (1998) was a 35-year-old male who had delayed developmental milestones,
only beginning to sit between the ages of two and three and commencing walking at four years. He did
not babble as a baby although he said single words inappropriately at six years of age. He did not make
eye contact, rarely smiled, and had little interest in his surroundings other than a fondness for a
specific record which he played repetitively. From the age of four he had little tolerance of other
people, apart from immediate family members, and frequently threw objects. He had limited
expressive language and although he had a few single words and short phrases, he did not use these
appropriately, and generally tended to point or take people to things if he required them. He also had
infrequent seizures. He fulfilled ICD-10 criteria for Childhood Autism. His overall level of functioning
was consistent with severe mental retardation.
 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839 835

6. Medical factors associated with a diagnosis of an ASD in an individual with Down syndrome

A number of case reports make reference to medical factors likely to be of importance in

contributing to the development of ASDs in individuals with Down syndrome. Although there does not
appear to be a single medical factor that contributed to presence of ASDs in Down syndrome, an
increased prevalence of medical difficulties may be associated with an increased risk of ASDs in this
population (Rasmussen, Börjesson, Wentz, & Gillberg, 2001). Eleven of the 25 participants in
Rasmussen et al.’s (2001) study of ASDs in Down syndrome had medical difficulties that may have
contributed to the development of ASDs. These included medical complications during pregnancy in
the form of vaginal bleeding, infantile spasms, early hypothyroidism, and evidence of brain injury after
complicated heart surgery.

7. Cognitive functioning in individuals with Down syndrome and ASDs

Most individuals with Down syndrome tend to function in the moderate range of mental
retardation (Connolly, 1978), with declines occurring as the children get older, and reach adulthood
(Hodapp, Evans, & Gray, 1999). The reported levels of cognitive functioning of children with Down
syndrome and co-morbid ASDs have varied, although there appears to be more children operating in
the severe and profound range than in the typical Down syndrome population. Two of four individuals
reported to have Down syndrome and an ASD in the Kent et al. (1999) study had moderate mental
retardation, one had mild-moderate mental retardation, and one had moderate-severe mental
retardation. A study by Ghaziuddin (2000) included 11 case reports of children with Down syndrome
and an ASD and of the 11, eight had a moderate level of mental retardation and three had a severe level
of mental retardation and three had a severe level of mental retardation. In a study of 25 individuals
with Down syndrome and an ASD (Rasmussen et al., 2001) one individual had a score in the borderline
range of functioning, three had mild mental retardation, four had a moderate mental retardation, 16
had severe mental retardation range, and one had mental retardation in the profound range. It must be
noted that three of the 25 individuals diagnosed with an ASD in this study had mosaicism, which is
associated with enhanced cognition in Down syndrome (Fishler & Koch, 1991).
In Capone et al.’s (2005) study, 87% of those with Down syndrome and an ASD were functioning in
the severe or profound range (IQ 0–39) of cognitive/developmental functioning. In comparison, most
of the typical Down syndrome comparison group were functioning in the moderate or severe range (IQ
25–54). Carter et al. (2007) reported that the individuals in their sample with Down syndrome and an
ASD were found to have a significantly lower IQ or IQ-equivalent scores than those with Down
syndrome without an ASD. The three children diagnosed with an ASD in the Hepburn et al. (2008)
study fell within the lower 20% of the IQ distribution of this sample of children with Down syndrome.
It is must be noted that a number of the children with Down syndrome and an ASD reported in the
literature were reported to be difficult to test or uncooperative during the assessment process and
therefore, were not assigned a level of cognitive functioning.

8. Gender ratio of individuals with Down syndrome and an ASD

Studies based on both clinical and epidemiological samples have found a higher incidence of ASDs
in males than females, with a reported ratio averaging around 3.5 or 4.0 to 1 for Autistic Disorder
(Fombonne, 2003). In terms of the ratio among Down syndrome population, Capone et al. (2005)
reported that of 73 persons with Down syndrome and co-morbid ASDs in the literature, 50 (73%) were
male, 18 (27%) were female, and the gender of five individuals was not reported. Lund (1988) reported
five individuals with Down syndrome and infantile autism, and of these four were male and one was
female. The three cases of Down syndrome and ASDs reported by Ghaziuddin et al. (1992) were male.
The report of Howlin et al. (1995) included case reports of four boys with Down syndrome and an ASD.
The three case reports described by Kent et al. (1998) were male. Kent et al. (1999) reported that of the
four children with Down syndrome who were diagnosed with an ASD in their sample, two were male
and two were female. The report of Ghaziuddin (2000) on the family history of individuals with Down
syndrome and an ASD included nine males and two females. Rasmussen et al. (2001) reported on 25
836 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839

individuals with Down syndrome and ASDs and of these, 12 were female and 13 were male. Starr et al.
(2005) reported on five individuals with Down syndrome, who could be considered to show an ASD,
and of these, four were male and one was female. Carter et al. (2007) reported a predominance of
males with Down syndrome diagnosed with an ASD in a male female ratio of approximately 4:1. Of the
ten individuals in a Brazilian screening study who the met the cut-off for Autistic Disorder, eight were
males and two were females, and of the 18 individuals who met the criteria for PDD-NOS, nine were
male and nine were female (Lowenthal et al., 2007). The two children who were given a clinical
diagnosis of ‘autism’ in Hepburn et al.’s (2008) study were male. A third child who met the criteria for
‘autism spectrum’ was female. In summary, the majority of individuals with Down syndrome co-
morbid for ASDs reported in the literature have been male, although it is possible this may reflect
under-diagnosing of females where perhaps professionals expect even less to diagnose an ASD (Kent
et al., 1999).

9. Family history of individuals with Down syndrome and ASDs

One of the documented risk factors among children with Down syndrome for ASDs has been family
history of the broader autism phenotype and/or a family history of psychiatric difficulties. Ghaziuddin
(2000) examined 11 subjects with Down syndrome who were diagnosed with Autistic Disorder based
on DSM-III-R criteria (APA, 1987). Family history was obtained from biological parents based on a
shorter version of the Family History Schedule (Bolton et al., 1994), an investigator-based interview
designed to identify the presence of developmental disorders, abnormalities of emotional
development, and psychiatric disorders in first and second degree relatives. Out of the 22 parents
in the Down syndrome plus autism group, seven parents (i.e., six fathers and one mother) met the
broader autism phenotype based on the Family History Schedule compared with one (7%) in the
control group of parents who had a child with Down syndrome without autism. Out of the 11
biological siblings in the Down syndrome plus autism group, two had a history of speech problems
severe enough to require treatment, two were labelled as having mental retardation and were placed
in special education, and one sibling had Down syndrome. There were also 11 biological siblings in the
Down syndrome without autism group, and none of these siblings had a history of communication or
social abnormalities severe enough to require specialised services. These findings suggest that autism-
specific genetic factors may explain why some individuals with Down syndrome, show the presence of
autism while others do not (Ghaziuddin, 2000). Rasmussen et al. (2001) reported that in 25 individuals
with Down syndrome plus autism, five individuals had one or more first or second-degree relatives
who had a diagnosis of autism, severe attention deficits, or learning disorders. In a further eight
participants there were similar problems among relatives but to a less severe degree, or there were
psychiatric disorders in the form of bipolar disorder.

10. Diagnosing ASDs in children/adults with Down syndrome

One of the issues regarding the identification of ASDs in Down syndrome is what instruments/
protocols should be adopted when undertaking a diagnostic evaluation. The presentation of children
with Down syndrome and ASDs may be different from that which professionals expect to find, based
on their previous experience of diagnosing ASDs in children without Down syndrome (Kent et al.,
1999). For example, some of the obsessional traits which may be seen in individuals with Down
syndrome may be related to ASDs if they are seen in combination with the social and language
difficulties associated with ASDs and may be qualitatively different than the Obsessive Compulsive
Disorder (OCD) type behaviors associated with Down syndrome (Kent et al., 1999). Another difficulty
in diagnosis is distinguishing between ASD type behaviors and essentially similar behaviors
associated with the level of mental retardation. A substantial number of people with Down syndrome
may display stereotyped behaviors, especially those functioning in severe or profound level of mental
retardation (Kraijer & De Bildt, 2005,) and disentangling stereotyped behaviors due to level of mental
retardation and that due to the presence of an ASD may be difficult. The influence of moderate to
severe hearing loss and communication impairment in young children with Down syndrome may
affect progress in social relationships and communication, further complicating the diagnostic picture.
 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839 837

Many of the commonly used ASD screening questionnaires include items covering language delay,
motor ‘clumsiness’, and friendships, which, if the user is not familiar with the development of children
with Down syndrome, may lead to over identification of children deemed to be ‘at risk’.
Despite the potential difficulties with diagnosing ASDs in individuals with Down syndrome, it is
important that clinicians undertake comprehensive evaluations of those deemed at risk for ASDs. All
individuals with Down syndrome at risk for an ASD should be evaluated using standardised diagnostic
instruments. It is important that standardised observational methods are used as well as diagnostic
interviews. The use of a structured ASD specific observational tool such as the Autism Diagnostic
Observational Schedule (ADOS; Lord et al., 1999) as well extended unstructured observations in
number of settings may be particularly pertinent. The use of a maladaptive behavior checklist, such as
the Aberrant Behavior Checklist (Aman et al., 1995) may also aid differential diagnosis. Special
attention needs to be given to a detailed developmental history because of the already abnormal
development associated with the mental retardation that is characteristic of Down syndrome (Kent
et al., 1998). However, even with the use of standardised instruments, the gold standard in this
population will be clinical diagnosis, based on the diagnostic decision made by a team of multi-
disciplinary clinicians experienced with working with both individuals with Down syndrome and
individuals with ASDs. In terms of diagnostic classification, it has been suggested that a diagnosis of
Childhood Disintegrative Disorder (CDD) should be considered for a proportion of individuals with
Down syndrome who are at risk of ASDs, although the prevalence of CDD in children with Down
syndrome has received little attention in the literature (Capone et al., 2005).

11. Conclusion

The finding of the co-occurrence of ASDs contrasts with the usual view of people with Down
syndrome as being sociable and outgoing. There are now a substantial number of studies to
demonstrate that a subgroup of individuals with Down syndrome meet the diagnostic criteria for an
ASD, and as a result are likely to need qualitatively different approaches in terms of supports and
interventions to maximise their educational potential and quality of life. Whether those with Down
syndrome and ASDs constitute a qualitatively different group of individuals with Down syndrome, or
there is a continuum of ASD behaviors among the Down syndrome population, has still to be
determined. Recent evidence from studies of individuals with fragile X syndrome suggests a spectrum
or continuum of autistic behaviors as opposed to a dichotomous classification into autism and non-
autism (Clifford et al., 2007). It has been suggested that studies of comorbidity of ASDs with genetic
conditions should extend beyond a clear-cut distinction between ‘autistic’ and ‘non-autistic’
categories, and consider the distributions of the full-range of ASD behavior scores on diagnostic
instruments (Loesch et al., 2007), and this approach is likely to be useful in contributing to an
increased understanding of the manifestation and extent of ASD behaviors in the Down syndrome
population. The delineation of specific behavioral profiles is important for the proper design and
implementation of therapeutic interventions for children with Down syndrome (Capone, 2004).
Despite the view, that once a child with Down syndrome is diagnosed with an ASD, treatment and
education strategies for children ASDs should be followed, there is a paucity of evidence in the
literature about response to treatment or educational strategies, which would be an important
contribution to the field (Hepburn et al., 2008). Kroeger and Nelson (2006) describe how a combined
treatment approach incorporating direct instruction, natural environment teaching, and incidental
teaching can be effective in increasing and maintaining responsive and spontaneous speech in a child
with Down syndrome diagnosed with autism, and there is a need for more studies on interventions for
this population. There is need for continued work to examine whether Down syndrome plus an ASD
constitutes ‘classic autism’, or whether an alternative explanation accounts for the social and
communication difficulties recognised as an ASD in this population (Hepburn et al., 2008). The impact
of developmental level on symptoms has not been adequately studied (Howlin et al., 1995) and
developmental level is likely to impact response to treatment. There is still much that is not known
about the manifestation of ASDs in individuals with Down syndrome and a total population
epidemiological sample of individuals with Down syndrome employing well validated diagnostic
tools is essential to further clarify prevalence rates of ASDs among those with Down syndrome.
838 C. Reilly / Research in Autism Spectrum Disorders 3 (2009) 829–839

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