low functioning autism spectrum...
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Low Functioning
Autism Spectrum Disorder
Walter E. Kaufmann Center for Translational Research
Greenwood Genetic Center Department of Neurology, Boston Children’s Hospital
MIT Simons Center for the Social Brain
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Disclosures
Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest
to disclose
• Consultant to Neuren, Edison, Newron, EryDel, Marinus, Echo Pharmaceuticals and
GW Pharmaceuticals.
• Research support from Ipsen and Eloxx.
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Low Functioning Autism Spectrum Disorder
DSM-5’s Impact on:
Intellectual Disability
&
Autism Spectrum Disorder
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Low Functioning Autism Spectrum Disorder
DSM-5 & Intellectual Disability:
Potential Decrease in Prevalence
9% decrease
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Low Functioning Autism Spectrum Disorder
DSM-5 & Autism Spectrum Disorder:
Selective Disorder, Not Explained by Cognitive Impairment
Autism Spectrum Disorder 51
E. These disturbances are not better explained by intellectual disability (intellectual devel-
opmental disorder) or global developmental delay. Intellectual disability and autism
spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spec-
trum disorder and intellectual disability, social communication should be below that ex-
pected for general developmental level.
Note: Individuals with a well-established DSM-IV diagnosis of autistic disorder, Asperger’s
disorder, or pervasive developmental disorder not otherwise specified should be given the
diagnosis of autism spectrum disorder. Individuals who have marked deficits in social
communication, but whose symptoms do not otherwise meet criteria for autism spectrum
disorder, should be evaluated for social (pragmatic) communication disorder.
Specify if:
With or without accompanying intellectual impairment
With or without accompanying language impairment
Associated with a known medical or genetic condition or environmental factor
(Coding note: Use additional code to identify the associated medical or genetic condition.)
Associated with another neurodevelopmental, mental, or behavioral disorder
(Coding note: Use additional code[s] to identify the associated neurodevelopmental,
mental, or behavioral disorder[s].)
With catatonia (refer to the criteria for catatonia associated with another mental dis-
order, pp. 119–120, for definition) (Coding note: Use additional code 293.89 [F06.1]
catatonia associated with autism spectrum disorder to indicate the presence of the co-
morbid catatonia.)
Recording ProceduresFor autism spectrum disorder that is associated with a known medical or genetic condition
or environmental factor, or with another neurodevelopmental, mental, or behavioral dis-
order, record autism spectrum disorder associated with (name of condition, disorder, or
factor) (e.g., autism spectrum disorder associated with Rett syndrome). Severity should be
recorded as level of support needed for each of the two psychopathological domains in
Table 2 (e.g., “ requiring very substantial support for deficits in social communication and
requiring substantial support for restricted, repetitive behaviors” ). Specification of “ with
accompanying intellectual impairment” or “ without accompanying intellectual impair-
ment” should be recorded next. Language impairment specification should be recorded
thereafter. If there is accompanying language impairment, the current level of verbal func-
tioning should be recorded (e.g., “ with accompanying language impairment—no intell igi-
ble speech” or “ w ith accompanying language impairment—phrase speech” ). If catatonia is
present, record separately “ catatonia associated with autism spectrum disorder .”
Specif iersThe severity specifiers (see Table 2) may be used to describe succinctly the current symp-
tomatology (which might fall below level 1), with the recognition that severity may vary by
context and fluctuate over time. Severity of social communication diff icul ties and re-
stricted, repetitive behaviors should be separately rated. The descriptive severity categories
should not be used to determine eligibility for and provision of services; these can only be
developed at an individual level and through discussion of personal priorities and targets.
Regarding the specifier “ with or without accompanying intellectual impairment,” un-
derstanding the (often uneven) intellectual profile of a child or adult with autism spectrum
disorder is necessary for interpreting diagnostic features. Separate estimates of verbal and
nonverbal ski l l are necessary (e.g., using untimed nonverbal tests to assess potential
strengths in individuals with limited language).
Autism Spectrum Disorder 51
E. These disturbances are not better explained by intellectual disability (intellectual devel-
opmental disorder) or global developmental delay. Intellectual disability and autism
spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spec-
trum disorder and intellectual disability, social communication should be below that ex-
pected for general developmental level.
Note: Individuals with a well-established DSM-IV diagnosis of autistic disorder, Asperger’s
disorder, or pervasive developmental disorder not otherwise specified should be given the
diagnosis of autism spectrum disorder. Individuals who have marked deficits in social
communication, but whose symptoms do not otherwise meet criteria for autism spectrum
disorder, should be evaluated for social (pragmatic) communication disorder.
Specify if:
With or without accompanying intellectual impairment
With or without accompanying language impairment
Associated with a known medical or genetic condition or environmental factor
(Coding note: Use additional code to identify the associated medical or genetic condition.)
Associated with another neurodevelopmental, mental, or behavioral disorder
(Coding note: Use additional code[s] to identify the associated neurodevelopmental,
mental, or behavioral disorder[s].)
With catatonia (refer to the criteria for catatonia associated with another mental dis-
order, pp. 119–120, for definition) (Coding note: Use additional code 293.89 [F06.1]
catatonia associated with autism spectrum disorder to indicate the presence of the co-
morbid catatonia.)
Recording ProceduresFor autism spectrum disorder that is associated with a known medical or genetic condition
or environmental factor, or with another neurodevelopmental, mental, or behavioral dis-
order, record autism spectrum disorder associated with (name of condition, disorder, or
factor) (e.g., autism spectrum disorder associated with Rett syndrome). Severity should be
recorded as level of support needed for each of the two psychopathological domains in
Table 2 (e.g., “ requiring very substantial support for deficits in social communication and
requiring substantial support for restricted, repetitive behaviors” ). Specification of “ with
accompanying intellectual impairment” or “ without accompanying intellectual impair-
ment” should be recorded next. Language impairment specification should be recorded
thereafter. If there is accompanying language impairment, the current level of verbal func-
tioning should be recorded (e.g., “ with accompanying language impairment—no intell igi-
ble speech” or “ w ith accompanying language impairment—phrase speech” ). If catatonia is
present, record separately “ catatonia associated with autism spectrum disorder .”
Specif iersThe severity specifiers (see Table 2) may be used to describe succinctly the current symp-
tomatology (which might fall below level 1), with the recognition that severity may vary by
context and fluctuate over time. Severity of social communication diff iculties and re-
stricted, repetitive behaviors should be separately rated. The descriptive severity categories
should not be used to determine eligibility for and provision of services; these can only be
developed at an individual level and through discussion of personal priorities and targets.
Regarding the specifier “ with or without accompanying intellectual impairment,” un-
derstanding the (often uneven) intellectual profile of a child or adult with autism spectrum
disorder is necessary for interpreting diagnostic features. Separate estimates of verbal and
nonverbal ski l l are necessary (e.g., using untimed nonverbal tests to assess potential
strengths in individuals with limited language).
CONFID
ENTIA
LIf Cognitive Impairment is Present, it Should Be Specified
Also problematic features leading mainly to false positive diagnosis: behavioral phenotypical features & psychiatric co-morbidities
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Low Functioning Autism Spectrum Disorder
ASD in DSM-5
The Challenge of Demonstrating Selectivity
Is there a problem with diagnosing ASD in ID?
Too Early to Be Definitive but
It Seems to Be the Case
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID (using DSM-5)?
Decreased prevalence of ASD affects less ID
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insights from Down syndrome, fragile X syndrome & Phelan-
McDermid syndrome
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insight from fragile X syndrome & Down syndrome
Level of Intellectual Disability is Associated with ASD Dx
Intellectual ability and adaptive behavior profiling: DQ/IQ
0
10
20
30
40
50
60
70
80
% o
f su
bje
cts
<25 25-39 40-54 55-70
Cognitive Level (IQ)
DS+ASD DS+SMD DS Typical
0
10
20
30
40
50
60
70
80
% o
f su
bje
cts
<25 25-39 40-54 55-70 70+
Cognitive Level (IQ)
FXS+ASD FXS Typical
Down Syndrome Fragile X Syndrome
Capone et al. Am J Med Genet 134A:373-380, 2005 Carter et al. Am J Med Genet 144B:87-94, 2007
Kaufmann et al. Am J Med Genet 129A:225-234, 2004 Budimirovic et al. Am J Med Genet 140A:1814-1826, 2006
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insight from fragile X syndrome
Variable prevalence of ASD in FXS
EMBARGOED – DO NOT COPY – DO NOT DISTRIBUTE CDC Cleared Paper – to be submitted to Pediatrics as part of FXS Supplement
6
relationship between FXS and ASD is complex and evolving, influenced in part by
revised definitions of ASD12
and by a better understanding of behavioral phenotypes
associated with FXS.6 Although variable in degree, a large proportion of individuals with
FXS exhibit poor eye contact, difficulties with peer relationships, social withdrawal,
repetitive behaviors, and need for sameness (i.e., distress at apparently small changes in
daily activities)6,13,14
. Depending on the gold standard research criteria used for the
diagnosis of autism or ASD, studies on males with FXS have reported that 30-54% met
diagnostic criteria for autism by direct assessment15-17
and 46% by parent report18
. In
addition, 30-43% of males met diagnostic criteria for ASD19
or Pervasive Developmental
Disorder-Not Otherwise Specified (PDD-NOS)17
. For females, 16-20% met diagnostic
criteria for autism16
or were assigned by parent report18
18-21
. Several studies have
attempted to delineate unique features of ASD in FXS; their findings show relatively
more prominent social withdrawal, higher levels of anxiety, and less intense simple and
complex repetitive and restricted behaviors as measured by ASD diagnostic
instruments6,22
.
ASD in FXS is associated with greater cognitive and behavioral impairment
ASD is a lifelong disorder, which impacts multiple aspects of the individual’s
functioning. Comparisons between subjects with ASD in FXS (FXS+ASD) and subjects
without ASD in FXS (FXS only) reveal that the former group is more affected in many
cognitive9,19,23
24
and behavioral areas6,7,13,14,22,25
. Examples of areas more problematic in
those with FXS+ASD than with FXS only include less developed language skills,
particularly receptive skills20,23,26,27
; lower non-verbal cognition and IQ scores28,29
; lower
Kaufmann et al. Pediatrics: in press
Even controversial diagnosis Journal of the American Academy of Child &
Adolescent Psychiatry
Volume 49, Issue 9, September 2010, Pages 921–933
New research
Autism in Fragile X Syndrome: A Category Mistake?
Scott S. Hall, Ph.D. , , Amy A. Lightbody, Ph.D., Melissa Hirt, M.A., Ava Rezvani, H.S., Allan L. Reiss,
M.D.
Show more
Autism in Fragile X Syndrome: A Category Mistake? http://www.sciencedirect.com/science/article/pii/S0890856710005265
1 of 4 12/24/16, 1:30 PM
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insight from fragile X syndrome Psychiatric co-morbidities may influence diagnosis
Hagerman et al. Pediatrics 123:378-390, 2009
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insight from fragile X syndrome
Decreased prevalence of ASD using DSM-5 (males: 29% SCI, 86% RRB)
Wheeler et al. J Autism Dev Disord 45:816-829, 2015
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID (using DSM-5)?
Insight from Phelan-McDermid syndrome
Over-diagnosis of ASD in PMS (90% SCI, 55% RRB)
Oberman et al. Orphanet J Rare Dis 10:105, 2015 Also Soorya et al. Mol Autism 4:18, 2013
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Insight from Down syndrome
Is the diagnosis of ASD in DS (7-15%) Valid? Cluster Analysis of ABC-C: Likely
Ji et al. J Intellect Disabil Res 55:1064-1077, 2011
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Data from FXS, PMS & DS: several factors may contribute
• Intellectual impairment • Unique behavioral phenotype features
• Psychiatric co-morbidities
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions
Intellectual impairment
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID? Potential Solutions
Intellectual ability and adaptive behavior profiling: DQ/IQ & AB
Kaufmann et al. Am J Med Genet 129A:225-234, 2004 Hernandez et al. Am J Med Genet 149A:1125-1137, 2009
ID is Inherent to ASD but Social rather than Communication skills predict Dx (& severity)
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions Intellectual ability and adaptive behavior profiling: AB
Oberman et al. Orphanet J Rare Dis 10:105, 2015
Relatively Preserved Social Domain: Lower Concern for ASD
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions
Behavioral Phenotype Features
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions Analysis of Behavioral Phenotype Features
• ASD in DS: Impairment in Nonverbal Social Communication (e.g., gestures)
• Non-ASD in DS: Stereotypic Behavior • ASD in FXS: Impairment in (Peer) Relationships • Non-ASD in FXS: Eye Gaze Avoidance, Social Anxiety • ASD in PMS: Abnormal Sensory Reactivity & Nonverbal
Social Communication Impairment • Non-ASD in PMS: Impairment in Social Communication
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions
Psychiatric Co-morbidities
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions Analysis of Psychiatric Co-Morbidities
• ASD in DS: Stereotypic Behavior (SMD) & ADHD-like behaviors
• ASD in FXS: Anxiety- & ADHD-like behaviors • ASD in PMS: Stereotypic Behavior (SMD) & ADHD-like
behaviors
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Low Functioning Autism Spectrum Disorder
Is there a problem with ASD Dx in ID?
Potential Solutions
Adapting Diagnostic Instruments
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Low Functioning Autism Spectrum Disorder
Is there a problem in ASD with ID?
Potential Solutions
Using ID- & syndrome-adapted instruments: DSM-5’s Novel Features
50 Neurodevelopmental Disorders
Autism Spectrum Disorder
Autism Spectrum Disorder
Diagnostic Criteria 299.00 (F84.0)
A. Persistent deficits in social communication and social interaction across multiple con-
texts, as manifested by the following, currently or by history (examples are illustrative,
not exhaustive; see text):
1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social
approach and failure of normal back-and-forth conversation; to reduced sharing of
interests, emotions, or affect; to failure to initiate or respond to social interactions.
2. Deficits in nonverbal communicative behaviors used for social interaction, ranging,
for example, from poorly integrated verbal and nonverbal communication; to abnor-
malities in eye contact and body language or deficits in understanding and use of
gestures; to a total lack of facial expressions and nonverbal communication.
3. Deficits in developing, maintaining, and understanding relationships, ranging, for ex-
ample, from difficulties adjusting behavior to suit various social contexts; to difficulties
in sharing imaginative play or in making friends; to absence of interest in peers.
Specify current severity:
Severity is based on social communication impairments and restricted, re-
petitive patterns of behavior (seeTable 2).
B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at
least two of the following, currently or by history (examples are illustrative, not exhaus-
tive; see text):
1. Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple
motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic
phrases).
2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns of
verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties
with transitions, rigid thinking patterns, greeting rituals, need to take same route or
eat same food every day).
3. Highly restricted, fixated interests that are abnormal in intensity or focus (e.g.,
strong attachment to or preoccupation with unusual objects, excessively circum-
scribed or perseverative interests).
4. Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of
the environment (e.g., apparent indifference to pain/temperature, adverse re-
sponse to specific sounds or textures, excessive smelling or touching of objects,
visual fascination with lights or movement).
Specify current severity:
Severity is based on social communication impairments and restricted, re-
petitive patterns of behavior (see Table 2).
C. Symptoms must be present in the early developmental period (but may not become
fully manifest until social demands exceed limited capacities, or may be masked by
learned strategies in later life).
D. Symptoms cause clinically significant impairment in social, occupational, or other im-
portant areas of current functioning.
CONFID
ENTIA
L
50 Neurodevelopmental Disorders
Autism Spectrum Disorder
Autism Spectrum Disorder
Diagnostic Criteria 299.00 (F84.0)
A. Persistent deficits in social communication and social interaction across multiple con-
texts, as manifested by the following, currently or by history (examples are illustrative,
not exhaustive; see text):
1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social
approach and failure of normal back-and-forth conversation; to reduced sharing of
interests, emotions, or affect; to failure to initiate or respond to social interactions.
2. Deficits in nonverbal communicative behaviors used for social interaction, ranging,
for example, from poorly integrated verbal and nonverbal communication; to abnor-
malities in eye contact and body language or deficits in understanding and use of
gestures; to a total lack of facial expressions and nonverbal communication.
3. Deficits in developing, maintaining, and understanding relationships, ranging, for ex-
ample, from difficulties adjusting behavior to suit various social contexts; to difficulties
in sharing imaginative play or in making friends; to absence of interest in peers.
Specify current severity:
Severity is based on social communication impairments and restricted, re-
petitive patterns of behavior (seeTable 2).
B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at
least two of the following, currently or by history (examples are illustrative, not exhaus-
tive; see text):
1. Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple
motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic
phrases).
2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns of
verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties
with transitions, rigid thinking patterns, greeting rituals, need to take same route or
eat same food every day).
3. Highly restricted, fixated interests that are abnormal in intensity or focus (e.g.,
strong attachment to or preoccupation with unusual objects, excessively circum-
scribed or perseverative interests).
4. Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of
the environment (e.g., apparent indifference to pain/temperature, adverse re-
sponse to specific sounds or textures, excessive smelling or touching of objects,
visual fascination with lights or movement).
Specify current severity:
Severity is based on social communication impairments and restricted, re-
petitive patterns of behavior (see Table 2).
C. Symptoms must be present in the early developmental period (but may not become
fully manifest until social demands exceed limited capacities, or may be masked by
learned strategies in later life).
D. Symptoms cause clinically significant impairment in social, occupational, or other im-
portant areas of current functioning.
CONFID
ENTIA
L
SCI
RRB
DSM-5
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Low Functioning Autism Spectrum Disorder
Is there a problem in ASD with ID? Potential Solutions
Using ID- & syndrome-adapted instruments: Selected DSM Items
DSM-IV-TR criteria (Combined AUC 0.923, prediction error rate 13.6%)
Pedersen et al. Child Psychiatry Hum Dev: Aug 24, 2016
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Low Functioning Autism Spectrum Disorder
Is there a problem in ASD with ID? Potential Solutions
Using ID- & syndrome-adapted instruments: SCQ & SRS in FXS
FXS SCQ Sensitivity 61%, Specificity 70% SRS Sensitivity 97%, Specificity 21%
54 0.2
61 0.272
66 0.333
68 0.359
70 0.386
72 0.41373 0.427 D =
75 0.456
77 0.484
78 0.499 C Y80 0.528
82 0.556
84 0.584
C
D
Y
=
0.00 0.25 0.50 0.75 1.00
1 - Specificity
0.00
0.25
0.50
0.75
1.00
Sen
sit
ivit
y
ROC Curve for SRS Total
Points labeled by: srs_t_tot_calc _cutpt_ _optcorr_ _optdist_ _opty_ _optsesp_
Sens - Spec
0.0
0.2
0.4
0.6
0.8
1.0S
en
s -
Sp
ec
Youden
0.00
0.05
0.10
0.15
0.20
0.25
Valu
e
Distance
0.6
0.7
0.8
0.9
1.0
Dis
tan
ce t
o 0
,1
Correct
0.45
0.50
0.55
0.60
0.65
Co
rrect
rate
50 60 70 80 90 100
SRS T score (calculated) - total
50 60 70 80 90 100
SRS T score (calculated) - total
Tentative SRS Cut-off: 73 (norm: 60)
Idiopathic ASD Correct Dx SCQ (+) 97%, SRS (+) 80% ADOS (+) 96%. ADI-R (+) 98% J Autism Dev Disord 42:257-265, 2012
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Low Functioning Autism Spectrum Disorder
Summary
• Too early to be definitive: Slight decrease in ASD Dx with DSM-5 (perhaps also decrease in ID Dx)
• The challenge of demonstrating selectivity: beyond communication and overall intellectual impairment
• Psychiatric co-morbidities & behavioral phenotype can also affect ASD Dx
• Evaluating intellectual ability is essential in ASD Dx • Considering psychiatric co-morbidities & behavioral
phenotype in ASD Dx • Using ID-, syndrome-adapted instruments
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Low Functioning Autism Spectrum Disorder
Acknowledgements
• Down Syndrome Team at the Kennedy Krieger Institute (G. Capone, J. Carter)
• Fragile X Team at the Kennedy Krieger Institute (D. Budimirovic, V. Talisa) & FXCRC (E. Berry-Kravis, S. Sherman, S. Kidd, R. Hagerman, D. Hessl, etc.)
• Phelan-McDermid Team at the Greenwood Genetic Center & Boston Children’s Hospital (L. Boccuto, L. Oberman, K. Phelan, S. Sarasua)
• MIT Simons Center colleagues (M. Sur, R. Jaenisch) • DSM-5 NDD Workgroup colleagues