Autism Spectrum Disorder & Phelan McDermid Syndrome Q&A
(Prepared under the direction of the Research Support Committee)
In the course of raising your child and learning more about his or her disorder, you may have developed an awareness of autism spectrum disorder (ASD) and its connection to Phelan McDermid Syndrome (PMS).
- What are autism spectrum disorders?
- What does that definition mean for our families?
- What causes autism spectrum disorder?
- If my child has PMS, does that mean he or she has ASD?
- Is ASD common in individuals with PMS?
- What is the science behind the relationship between PMS and ASD?
- Does the ASD diagnosis replace my child’s diagnosis of PMS?
- What does it mean if my child does not have the characteristics of ASD?
- Why does autism matter to our Foundation?
- What does the Research Support Committee (RSC) think about the connection between PMS and ASD?
- Does a diagnosis of ASD help my child in any way?
- Does the ASD diagnosis help my child medically?
- How is ASD diagnosed?
- Should my child be evaluated for ASD?
- How can I learn more about PMS and its connection to ASD?
1) What are autism spectrum disorders? Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication and restricted or repetitive behavior. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association includes five conditions as ASDs. These are (1) autistic disorder, or classic autism; (2) Asperger’s Disorder; (3) Childhood Disintegrative Disorder; (4) Pervasive Developmental Disorder – Not Otherwise Specified (PDD-NOS); and (5) Rett syndrome.
2) What does that definition mean for our families? There are five recognized forms of “Autism”. All of them produce at least these two adverse effects: (1) social interaction and social communications are impaired, and (2) behavior is either restricted (fewer than normal behaviors) or is highly repetitive (too focused on one behavior or topic of interest). Because these critical features of autism frequently occur in children who have been diagnosed with PMS (and for other scientific reasons), it has become apparent that PMS and ASDs are closely related. Further research is needed to determine whether or not PMS will eventually be classified as another form of ASD.
3) What causes autism spectrum disorder? ASD is a disorder of prenatal or postnatal brain development. Although ASD can result from genetic or non-genetic causes, it is primarily a genetic disorder involving multiple genes. Most causes of ASD have not yet been identified. Many chromosome abnormalities and single gene mutations can result in ASD. PMS is one of the genetic disorders that is strongly associated with ASD.
4) If my child has PMS, does that mean he or she has ASD? It is quite possible. At present, ASD is a clinical diagnosis made by the observation and identification of key neurodevelopmental features listed in the DSM IV (see criteria below). Not all of the children with PMS have been diagnosed with ASD. There has been a reluctance by some clinicians to diagnose ASD when there is already another prior genetic diagnosis (like PMS), but the DSM-IV specifically permits dual diagnosis.
5) Is ASD common in individuals with PMS? Yes, many individuals with PMS have a diagnosis of ASD.
6) What is the science behind the relationship between PMS and ASD? PMS is highly associated (99%) with the loss of SHANK3 (a gene crucial for learning and memory). The exact same gene is affected in certain groups of people with ASD, including some individuals with Asperger’s Disorder and others with PDD-NOS. Further, SHANK3 is highly associated with a large group of neuronal adhesion and structure proteins also implicated in ASD.
7) Does the ASD diagnosis replace my child’s diagnosis of PMS? No. About 10% of individuals with ASD have a known cause (such as a chromosome deletion) for their diagnosis of ASD. The genetic diagnosis of 22q13 deletion, or PMS, describes your child’s genetic condition which may include neurodevelopmental features of ASD. The ASD diagnosis describes the behavioral, social, and communication characteristics of your child and is not excluded by a diagnosis of PMS.
8) What does it mean if my child does not have the characteristics of ASD? There is still a lot of debate when to diagnose ASD. Your child may have characteristics of ASD, but not be diagnosed as being on the autism spectrum. Diagnosis by behaviors is often difficult and inexact; clinicians unfamiliar with PMS may be reluctant to make the ASD diagnosis. There is an amazing range of behavioral differences among individuals with PMS, and some do not show significant signs of ASD. Scientists are still trying to determine how people with such similar genetics can be so different. The phenotype of PMS is very heterogeneous (variable from person to person), but what unites our families is a shared genetic diagnosis.
9) Why does autism matter to our Foundation? ASD has become important to our foundation because of the overlap in many of the associated neurological symptoms it shares with PMS. ASD has been diagnosed in many children with PMS, and understanding PMS is now widely recognized as a potential step toward understanding more about ASD. Most of our families are struggling with daily challenges which are commonly seen in ASD, such as limited communication skills, problem behaviors, restricted interests, toilet training difficulty, sleep problems, and other challenges. The Foundation encourages exchange of information among families and strives to keep families informed of medical, genetic, and behavioral advances that could help families address the challenges of ASD.
10) What does the Research Support Committee (RSC) think about the connection between PMS and ASD? There is definitive scientific evidence that loss or mutation of the SHANK3 gene is a genetic cause of ASD. SHANK3 resides on chromosome 22 within the region that is almost always deleted in PMS. In other words, the missing gene that causes the features of PMS is also a recognized cause of ASD. Understanding SHANK3 in the context of its molecular pathway and its relationship to related conditions, including other causes of ASD, could someday lead to treatments for PMS and other forms of ASD. The RSC also wants to see that professionals better understand the standards for diagnosing ASD in individuals with PMS.
11) Does a diagnosis of ASD help my child in any way? Such a diagnosis could help your child in two ways. First, there may be easier or greater access to educational and community services and programs with a diagnosis of ASD. In some cases certain programs are unavailable without the ASD diagnosis. Second, choosing appropriate therapies for a child are best done with the most complete diagnosis.
12) Does the ASD diagnosis help my child medically? The American Academy of Pediatrics (AAP) has published guidelines for the management of children with autism spectrum disorders. The full text article can be found at: http://www.aap.org/pressroom/issuekitfiles/ManagementofChildrenwithASD.pdf. Based on the medical histories and common experiences among our families, the following are some of the AAP guidelines directly applicable to PMS.
- Behavior and Education: The AAP guidelines include recommendations for early, intensive educational and behavioral interventions, with a low student-to-teacher ratio and a high degree of structure. The guidelines recommend Applied Behavior Analysis as a specific strategy, as well as Structured Teaching (TEACCH method). Speech therapy and social skills training are also recommended.
- Seizures: Because of the high prevalence of epilepsy in individuals with autism spectrum disorder, the AAP recommends that “a high index of clinical suspicion should be maintained and EEG [electroencephalography, a type of test to look at brain activity] should be considered when there are clinical spells that might represent seizures.”
- Gastrointestinal Problems: There are some reports that individuals with ASD might have more gastrointestinal problems, but “the existing literature does not support routine specialized gastroenterological testing for asymptomatic children with ASDs. However, if a child with an ASD presents with symptoms such as chronic or recurrent abdominal pain, vomiting, diarrhea, or constipation, it is reasonable [for a physician] to evaluate the gastrointestinal tract.”
- Sleep Disturbance: Sleep disturbance is a common problem in individuals with ASD. The AAP recommends that assessment and treatment of sleep problems should be guided by history and physical examination. Treatments might be targeted at identifiable medical causes of sleep disturbance (such as apnea or gastroesophageal reflux). In some cases behavioral interventions might be recommended. There is some evidence that melatonin is effective. Other medications are sometimes used to treat insomnia.
- Family Support: The AAP states “[s]upporting the family and ensuring its emotional and physical health is an extremely important aspect of overall management of ASDs.” Physicians are encouraged to support families by educating them about ASDs, assisting them in obtaining access to resources, and making referrals for other services.
13) How is ASD diagnosed? Diagnosis of ASD is made through observation of certain characteristics. The diagnostic criteria for ASD from the Diagnostic and Statistical Manual of Mental Disorders: DSM IV are included below. The criteria are very specific, but applying the criteria is subjective. The diagnosis must be made by a qualified professional (often a psychologist). Also, there is a misconception among some professionals that PMS somehow preempts a diagnosis of ASD.
There are two ways of being evaluated for ASD: through the educational system or through the medical system. The educational evaluation will likely include a parent interview as well as an assessment of your child. The evaluation will help the educational team determine if your child is eligible to receive special education services as a student with ASD. An evaluation through the medical system (or a clinical evaluation) will also likely include a parent interview and an assessment of your child. The clinical evaluation might be useful in cases where the school district is reluctant to do an ASD assessment and/or if you live in a state where Applied Behavior Analysis (ABA) is covered by insurance
There are several commonly-used tests which help diagnosticians objectively evaluate the characteristics outlined in the DSM-IV. The ADOS-R (Autism Diagnostic Observation Schedule), the ADI-R (Autism Diagnostic Interview-Revised), the CARS (Childhood Autism Rating Scale), and the GARS (Gilliam Autism Rating Scale) are commonly-used diagnostic tools.
14) Should my child be evaluated for ASD? Yes. The association between PMS and ASD is strong enough that a child with PMS should be evaluated for ASD.
15) How can I learn more about PMS and its connection to ASD? There have been numerous scientific articles published about PMS and its connection to ASD. Listed below are a few.
- Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F,et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39:25-27. http://www.nature.com/ng/journal/v39/n1/abs/ng1933.html (this is an abstract)
- Moessner R, Marshall CR, Sutcliffe JS, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81:1289-1297. (Here is is the full text article)
- Phelan MC. Deletion 22q13.3 syndrome. Orphanet Journal of Rare Diseases 2008;3:14. http://www.ojrd.com/content/3/1/14 (this is a full text article)
Diagnostic Criteria for Pervasive Developmental Disorders
The Diagnostic and Statistical Manual of Mental Disorders: DSM IV
Copied from http://www.agre.org/
299.00 Autistic Disorder
(A) total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3):
- qualitative impairment in social interaction, as manifested by at least two of the following:
(a) marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction
(b) failure to develop peer relationships appropriate to developmental level
(c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)
(d) lack of social or emotional reciprocity
- qualitative impairments in communication as manifested by at least one of the following:
(a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gestures or mime)
(b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others
(c) stereotyped and repetitive use of language or idiosyncratic language
(d) lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level
- restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:
(a) encompassing preoccupation with one or more stereotyped patterns of interest that is abnormal either in intensity or focus
(b) apparently inflexible adherence to specific, nonfunctional routines or rituals
(c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)
(d) persistent preoccupation with parts of objects
(B) Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play.
(C) The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder.
299.80 Rett's Disorder
(A) All of the following:
- apparently normal prenatal and perinatal development
- apparently normal psychomotor development through the first 5 months after birth
- normal head circumference at birth
(B) Onset of all of the following after the period of normal development:
- deceleration of head growth between ages 5 and 48 months
- loss of previously acquired purposeful hand skills between ages 5 and 30 months with the subsequent development of stereotyped hand movements (e.g., hand-wringing or hand washing)
- loss of social engagement early in the course (although often social interaction develops later)
- appearance of poorly coordinated gait or trunk movements
- severely impaired expressive and receptive language development with severe psychomotor retardation
299.10 Childhood Disintegrative Disorder
(A) Apparently normal development for at least the first 2 years after birth as manifested by the presence of age-appropriate verbal and nonverbal communication, social relationships, play, and adaptive behavior.
(B) Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:
- expressive or receptive language
- social skills or adaptive behavior
- bowel or bladder control
- motor skills
(C) Abnormalities of functioning in at least two of the following areas:
- qualitative impairment in social interaction (e.g., impairment in nonverbal behaviors, failure to develop peer relationships, lack of social or emotional reciprocity)
- qualitative impairments in communication (e.g., delay or lack of spoken language, inability to initiate or sustain a conversation, stereotyped and repetitive use of language, lack of varied make-believe play)
- restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, including motor stereotypies and mannerisms
(D) The disturbance is not better accounted for by another specific Pervasive Developmental Disorder or by Schizophrenia.
299.80 Asperger's Disorder
(A) Qualitative impairment in social interaction, as manifested by at least two of the following:
- marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction
- failure to develop peer relationships appropriate to developmental level
- a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people(e.g., by a lack of showing, bringing, or pointing out objects of interest to other people)
- lack of social or emotional reciprocity.
(B) Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:
- encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus
- apparently inflexible adherence to specific, non-functional routines or rituals
- stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)
- persistent preoccupation with parts of objects
(C) The disturbance causes clinically significant impairment in social, occupational, or other important areas of functioning.
(D) There is no clinically significant general delay in language (e.g., single words used by age 2 years, communicative phrases used by age 3 years)
(E) There is no clinically significant delay in cognitive development or in the development of age-appropriate self-help skills, adaptive behavior (other than in social interaction), and curiosity about the environment in childhood.
(F) Criteria are not met for another specific Pervasive Developmental Disorder or Schizophrenia.
299.80 Pervasive Developmental Disorder Not Otherwise Specified (Including Atypical Autism)
This category should be used when there is a severe and pervasive impairment in the development of reciprocal social interaction or verbal and nonverbal communication skills, or when stereotyped behavior, interests, and activities are present, but the criteria are not met for a specific Pervasive Developmental Disorder, Schizophrenia, Schizotypal Personality Disorder, or Avoidant Personality Disorder. For example, this category includes atypical autism --- presentations that do not meet the criteria for Autistic Disorder because of late age of onset, atypical symptomatology, or subthreshold symptomatology, or all of these.