A case study of autism spectrum disorder (ASD) symptomatology in a child with 15q13.3 deletion and Williams syndrome Faye van der Fluit & Bonita P. KleinTasman
Journal of Developmental and Physical Disabilities ISSN 1056-263X J Dev Phys Disabil DOI 10.1007/s10882-014-9404-2
1 23
Your article is protected by copyright and all rights are held exclusively by Springer Science +Business Media New York. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com”.
1 23
Author's personal copy J Dev Phys Disabil DOI 10.1007/s10882-014-9404-2 O R I G I N A L A RT I C L E
A case study of autism spectrum disorder (ASD) symptomatology in a child with 15q13.3 deletion and Williams syndrome Faye van der Fluit & Bonita P. Klein-Tasman # Springer Science+Business Media New York 2014
Abstract A variety of genetic disorders of known etiology present with behavioral profiles similar to that described in autism spectrum disorders (ASDs). Although some of these disorders are more likely to be associated with a comorbid ASD diagnosis, there exist cases in which there is a lack of empirical evidence to support a dual diagnosis. Two disorders, Williams syndrome (WS) and 15q13.3 deletion syndrome, have both been reported in the literature as examples of this phenotypic overlap. We present a case study of a young child with both WS and 15q13.3 deletion syndrome and significant ASD-related symptomatology. The results of a developmental evaluation, specifically the rationale for ruling out a comorbid ASD, are the focus of the present report. Implications for careful diagnostic consideration in cases of patients with known genetic conditions are also discussed. Keywords Autism spectrum disorders . Behavioral phenotype . Chromosome 15q13.3 Microdeletion Syndrome . Williams Syndrome
Introduction Within the behavioral genetics literature, many syndromes have been described as having significant behavioral overlap with autism spectrum disorders (ASDs). Examples of such disorders include (but are not limited to) Down, Fragile X, Angelman, and Smith-Magenis syndrome, as well as Tuberous Sclerosis complex (see Cohen et al. 2005 for a review). However, many of these reports are limited by the typical issues in genetics research, as well as the lack of the use of empirically supported diagnostic instruments. The use of “gold standard” measures is essential when discussing the symptomatology of ASDs. We present a case study of a child with both 15q13.3 deletion syndrome and Williams syndrome (WS), both of which have been described in the literature as showing behavioral similarities to ASDs, although to different degrees and in different ways. F. van der Fluit (*) Oregon Health and Science University, Portland, OR, USA e-mail:
[email protected] B. P. Klein-Tasman University of Wisconsin, Milwaukee, WI, USA
Author's personal copy J Dev Phys Disabil
Sharp and colleagues (2008) were the first group to report on the behavioral phenotype of a group of individuals with 15q13.3 deletion syndrome. The nine subjects identified presented with mild to moderate intellectual disability and facial dysmorphologies; one patient was also described to have “mild autism.” Further investigations of phenotypic expression have confirmed the presence of developmental delay or cognitive impairment in the majority, but not all, of affected individuals, as well as receptive and expressive language delays and symptoms of ASDs, particularly repetitive behavior and restricted interests (Ben-Shachar et al. 2009; Pagnamenta et al. 2009). Given reports of behavior similarities with ASDs in other disorders stemming from deletions (e.g., Prader-Willi and Angelman syndromes) or duplications in this region (Kwasnicka-Crawford et al. 2007; Hogart et al. 2010; Bolton et al. 2001; Boyar et al. 2001; Browne et al. 1997), disruption of genes within this region appears to confer risk for ASD. WS is a neurodevelopmental disorder resulting from the deletion of approximately 25 genes on chromosome 7q11.23 and is an additional condition of known genetic etiology with behavioral overlap with the autism spectrum. Although individuals with WS are often described as socially outgoing and overly friendly (Dilts et al. 1990; Gosch and Pankau 1997; Klein-Tasman and Mervis 2003), a pattern of deficits in individual social skills and functioning is also present. Young children with WS have difficulty with joint attention and social referencing (Laing et al. 2002); older children are reported to have difficulties with conversation (Stojanovik 2006) and social reciprocity (Klein-Tasman and Mervis 2003, 2011). On a diagnostic measure specifically designed to capture behaviors indicative of an ASD, children with WS demonstrate difficulties in various behaviors that overlap with the autism spectrum (Lincoln et al. 2007; Klein-Tasman et al. 2007; Klein-Tasman et al. 2009). Klein-Tasman and colleagues (2007) reported that young children with WS and limited language commonly demonstrate atypical eye contact and difficulty in the use of pointing and other gestures to communicate. A follow-up study (Klein-Tasman et al. 2009) using control groups of children with PDD-NOS and autism found that children with WS who were classified “ASD” or “autism” on this measure demonstrated similar difficulties to children with PDD-NOS. More recently, there have been other investigators who have also reported ASD symptoms in individuals with WS, such as repetitive behavior (Rodgers et al. 2012; see Asada and Itakura 2012 for a review). We present a case of a young child diagnosed with both 15q13.3 deletion syndrome and WS with significant behavioral overlap with the autism spectrum. Results of a comprehensive diagnostic evaluation are presented, with specific focus on differential diagnosis of an ASD in light of the known behavioral phenotype of both 15q13.3 deletion syndrome and WS. Additional data from two subsequent evaluations are also included.
Materials and Methods “Sam” was a male with WS and 15q13.3 deletion who was evaluated at age 3 years 11 months due to concerns about a possible comorbid ASD diagnosis. He was the product of an uncomplicated twin gestation, delivered via planned cesarean section at 36 weeks gestation. Perinatal complications included jaundice, high respiration rate,
Author's personal copy J Dev Phys Disabil
and heart murmur. Both WS (del(7)(q11.23) and 15q13.3 deletion syndrome were diagnosed at 17 months using fluorescence in situ hybridization (FISH) as well as chromosomal microarray analysis. Medical records indicated that cardiac complications, which are common in WS, included minimal pulmonary stenosis and stable supravalvular aortic stenosis. Motor milestones were reported to be somewhat delayed (sat at 10 months, stood at 20 months, walked at 34 months), while language milestones were considerably delayed (first words at 3 years 6 months, no use of phrases at time of evaluation at 3 years 11 months). At the time of this evaluation, Sam had been attending a special education preschool for approximately 1 year, where he received occupational, physical, and speech therapy. Additional physical and speech therapy were provided in a private setting and, in the case of speech therapy, at a university based clinic using an applied behavior analysis (ABA) approach. A comprehensive developmental assessment was conducted under a study approved by the institutional review board of the University of Wisconsin, Milwaukee. Informed consent was obtained from the child’s parents. The following instruments were included. Mullen Scales of Early Learning (MSEL) The MSEL (Mullen 1995) is a measure of developmental level, meant for use with children from 0 months to 5 years of age. Domain scores are reported as T-scores (M=50, SD=10). Overall performance is measured by the Early Learning Composite (ELC), which is reported as a standard score (M=100, SD=15). Differential Ability Scales, 2nd Edition (DAS-II) The DAS-2 (Elliot 2007) is a measure of cognitive abilities, meant for use with children from 2 years, 6 months of age through 17 years, 11 months. Overall performance is measured by the General Conceptual Ability (GCA), which is reported as a standard score (M=100, SD=15). Autism Diagnostic Interview-Revised (ADI-R) The ADI-R (Rutter et al. 2003) is a semi-structured caregiver interview administered by a trained clinician designed to gain information related to communication skills, reciprocal social interactions, and repetitive and restricted patterns of behavior. A subset of the items, which were previously determined to be most likely to distinguish between individuals with ASDs and those without, are then included in the total scoring algorithm. A cutoff for an “autism” classification is provided in each of the three domains, with “autism” classification when the cutoff is exceeded in all domains and the age of onset is prior to age 3. Autism Diagnostic Observation Schedule-Generic (ADOS-G) The ADOS-G (Lord et al. 1999) is a structured play observation administered by a trained examiner designed to elicit communication and reciprocal social interactions. Module 1 is administered to individuals with no speech or use of single words. Communicative overtures, reciprocal social interactions, and restricted and repetitive behaviors are coded according to descriptions provided. A subset of the items, empirically determined to be most likely to distinguish between individuals with ASDs and those without, are then included in the total scoring algorithm. Two cutoff totals are provided in communication (COM) and reciprocal social interaction (RSI) domains, as well as for the total score (TOT), consistent with an “ASD” classification or an “autism”
Author's personal copy J Dev Phys Disabil
classification. Recently reported revised algorithms (Gotham et al. 2007; Gotham et al. 2008) include a social affect domain (SA) and a social affect plus restricted interests and repetitive behaviors domain (SA + RRB), with both “ASD” and “autism” classifications. In addition, recently published ratings (Gotham et al. 2009) are available to compute the severity of autism spectrum symptomatology.
Results Raw scores and corresponding standard scores, when applicable, as well as autism diagnostic measure classifications, are summarized in Table 1. Cognitive Functioning Results of the developmental assessment revealed moderate delays in cognitive abilities across all areas. Mullen T-scores were at floor, such that age equivalents were examined for a sense of developmental level, ranging from 16 months (Visual Reception and Expressive Language domains) to 22 months (Receptive Language domain). Autism Diagnostic Instruments Sam’s parents reported a significant number of symptoms in the communication and repetitive behaviors domains such that his classification in these domains was “autism.” However, in the reciprocal social interactions domain, Sam’s behavior was classified “non-spectrum.” They reported that his use of spoken language was minimal and that he had only recently begun using gestures that were typically well rehearsed. His play skills were described as limited and quite repetitive, consisting mainly of stereotypical play with objects. Sensory interests, such as mouthing and smelling objects, hand and finger mannerisms, and whole body stereotypic movements were also described. Sam’s parents reported a number of reciprocal social strengths, such as consistent eye contact across settings and individuals, as well as social smiling and response to the smiles of others. He regularly sought out others in order to share his enjoyment in activities and used vocalizations and eye contact in Table 1 Summary of scores from initial evaluation MSEL Visual Reception Fine Motor Receptive Language Expressive Language Early Learning Composite ADI Reciprocal Social Interactions Communication Restricted & Repetitive Behavior Abnormality Evident Before 36 Months ADOS Original Algorithm Communication Reciprocal Social Interactions Total Revised Algorithm Social Affect Social Affect + Restricted & Repetitive Behavior
Raw Score 21 18 22 16 Score 7 14 4 5 Score
T-score/Standard Score
