Opportunities for ABA intervention in Phelan–McDermid syndrome

Abstract

Phelan–McDermid syndrome (PMS), also called 22q13.3 deletion syndrome, is a rare genetic disorder affecting at least 2,000 people worldwide (Phelan–McDermid Syndrome Foundation, 2019, How rare is Phelan–McDermid?). PMS has many distinguishing characteristics and many medical specialties have been recommended to treat the clinical features. While many therapies, including behavioral therapy, have been speculated to be beneficial in treating PMS, there is little known regarding their effectiveness [Costales, J. L. and Kolevzon, A. 2015. Phelan–McDermid syndrome and SHANK3: Implications for treatment. Neurotherapeutics: The Journal of the American Society for Experimental Neurotherapeutics, 12, 620–630.]. Behavior analysis has the capability to help in many areas of treatment for PMS either directly through, for example, behavior treatment to address aggressive behavior, or through collaborating with other specialties treating PMS by combining, for example, behavioral principles in the alleviation of medical issues such as constipation. Currently, there is a role for the behavior analyst to expand our field and identify effective treatments for those with PMS while we wait for a cure. In this paper, we discuss how medical considerations may affect behavior interventions and make recommendations for the behavior analyst working with PMS.

Phelan–McDermid Syndrome (PMS) is a genetic disorder impairing the ability of neurons to transmit signals effectively (Phelan and McDermid 2012, Kolevzon et al. 2014a, Costales and Kolevzon 2015). The genetic specificities have only as of relatively recently been identified, and several genetic methods of confirming the diagnosis are now available (Kolevzon et al. 2014a). Evaluation and treatment of the various clinical features of PMS is typically conducted by professionals in the fields of clinical genetics, molecular genetics, psychiatry, psychology, neurology, endocrinology, nephrology, cardiology, gastroenterology, and developmental pediatrics/primary care (Kolevzon et al. 2014a). Along with assessments, several treatments are recommended including occupational, physical, feeding, speech, and behavioral therapies (Phelan and McDermid 2012). Though these therapies have been recommended to treat PMS, there is little known about their effectiveness when working with these clients (Costales and Kolevzon 2015). Medical concerns related to PMS can influence behavioral interventions, both in terms of behavioral issues and effects on treatment gains and is thus the focus of this paper.

Considerations in behavioral interventions

While applied behavior analysis (ABA) has primarily been used with the autism spectrum disorder (ASD) client, clients with other genetic syndromes that present with intellectual disabilities and coexisting medical conditions, such as Down syndrome (Athens et al. 2008), Prader–Willi syndrome (Maglieri et al. 2000), Angelman syndrome (Fichtner and Tiger 2015), and Lesch–Nyhan syndrome (Obi 1997) have also benefitted. Behavioral principles do not change across clients; however, practitioners who are new to working with the PMS client might not recognize specific features of the disorder that differ from those in ASD, leading them to misinterpret treatment results. Those with PMS commonly experience comorbid medical issues that might require medication, and practitioners will need to know how side effects might impact treatment. Practitioners will also need to consider idiosyncrasies when planning and providing treatment.

PMS can present with several accompanying medical complications (see Kolevzon et al. 2014a, Phelan and McDermid, 2012 for a thorough review). Dental problems—including tooth grinding and tongue thrusting—and poor muscle tone in the face and throat can lead to feeding issues. Other contributors to feeding problems can include restrictive diets, pica, gastroesophageal reflux, constipation and/or diarrhea, and urinary reflux. Toileting issues might arise due to these conditions, along with urinary tract infections and low muscle tone. Motor issues can also develop due to poor muscle tone, which can result in reduced reflexive responding, delayed motor milestones, speech impairments, and unstable or delayed gait. The individual’s abilities to complete daily living skills can also be impacted by motor delays. Intellectual disabilities such as delayed or absent speech might contribute to reduced social interaction and poor eye contact. In combination, motor issues and intellectual disabilities can reduce the individual’s ability to function independently in their community (e.g. public transportation skills). Delays or difficulties in verbal behavior could impair the individual’s ability to make illness known to others (e.g. upper respiratory tract infections, pain from ear infections, vision or hearing problems, instances of seizures, or overheating due to a decreased ability to sweat). Additional medical conditions to monitor are congenital heart defects, swelling of lymph nodes, and undeveloped or underdeveloped kidneys. Finally, these conditions might contribute to the development of anxious behavior (e.g. rapid breathing) and sleep disturbances, which can increase abnormal behavior such as repetitive self-stimulatory actions or aggressive behavior (see Table 1 for a reference list of documented behavioral issues in the literature). The behavior analyst can help directly alleviate some of these issues or indirectly assist medical teams by introducing behavior–analytic interventions to increase tolerance of medical treatments.

Table 1.

Behavioral issues in PMS¹ and sources for reference.

Behavioral issue	Sources
Adaptive behavior	Darville et al. (2016)
Aggression	Pasini et al. (2010), Serret et al. (2015), Vucurovic et al. (2012)
Agitation/Irritability	Verhoeven et al. (2013), Verhoeven et al. (2012)
Attention issues	Denayer et al. (2012), Egger et al. (2017), Egger et al. (2016), Verhoeven et al. (2012), Vucurovic et al. (2012)
Catatonia	Ballesteros et al. (2017), Denayer et al. (2012), Messias et al. (2013), Serret et al. (2015)
Communication	Denayer et al. (2012), Egger et al. (2017), Egger et al. (2016), Messias et al. (2013), Schmidt et al. (2009), Verhoeven et al. (2012), Vucurovic et al. (2012), Zwanenburg et al. (2016)
Compulsive urination and masturbation in public	Vucurovic et al. (2012)
Daily living skills2	Denayer et al. (2012), Messias et al. (2013), Schmidt et al. (2009)
Developmental functioning	Egger et al. (2016)
Disinhibited behavior	Verhoeven et al. (2012), Vucurovic et al. (2012)
Disruptive behavior	Denayer et al. (2012)
Eloping	Vucurovic et al. (2012)
Emotional issues	Zwanenburg et al. (2016)
Executive functioning	Egger et al. (2016), Verhoeven et al. (2012)
Feeding	Messias et al. (2013), Omansky et al. (2017)
General functioning	Ballesteros et al. (2017), Messias et al. (2013), Schmidt et al. (2009)
Hyperactivity	Vucurovic et al. (2012)
Impulsivity	Serret et al. (2015), Verhoeven et al. (2012), Vucurovic et al. (2012)
Independence	Messias et al. (2013), Schmidt et al. (2009)
Information processing	Egger et al. (2016)
Motor agitation	Verhoeven et al. (2012)
Motor functioning	Egger et al. (2017), Schmidt et al. (2009), Zwanenburg et al. (2016)
Obsessive traits/rituals	Denayer et al. (2012), Verhoeven et al. (2012)
Psychomotor agitation	Denayer et al. (2012), Pasini et al. (2010), Vucurovic et al. (2012)
Rigidity	Denayer et al. (2012)
Self-absorbed behavior	Denayer et al. (2012)
Sleep issues	Denayer et al. (2012), Egger et al. (2017), Messias et al. (2013), Pasini et al. (2010), Serret et al. (2015), Verhoeven et al. (2013), Verhoeven et al. (2012), Vucurovic et al. (2012)
Social issues	Denayer et al. (2012), Kolevzon et al. (2014b), Schmidt et al. (2009), Verhoeven et al. (2012), Vucurovic et al. (2012), Zwanenburg et al. (2016)
Stereotypic behaviors	Denayer et al. (2012), Kolevzon et al. (2014b), Verhoeven et al. (2013), Verhoeven et al. (2012)
Toileting issues	Denayer et al. (2012), Egger et al. (2017), Serret et al. (2015), Vucurovic et al. (2012)
Unpredictable outburst	Denayer et al. (2012)

Note. Table 1 is provided as a tool to reference sources that have described specific behavioral issues. While Table 1 is a frequency count of how often the above issues are mentioned in the literature, it does not depict the frequency of the actual behavioral issues. While disruptive behavior may seem to be less frequent from Table 1, it may only be that other issues are more attractive to write about. Behavioral issues were retained from articles found in a systematic literature review (Schroeder 2018).

¹ Phelan–McDermid syndrome (PMS).

² Daily living skills includes dressing and bathing for the purposes of this table.

Currently, there is no literature of behavior–analytic interventions regarding PMS, though the behavioral challenges facing the PMS community parallels those behavior analysts routinely address. Some of the behavioral research that could benefit the PMS population includes teaching tolerance to needed dental appointments (O'Callaghan et al. 2006) and developing effective feeding regimens (Volkert and Vaz 2010). Behavior analysts could help increase toileting (Kroeger and Sorensen-Burnworth 2009), motor (Miller et al. 2015), daily living (Pierce and Schreibman 1994), communication (Ghaemmaghami et al. 2018), social (Stauch et al. 2018), play (Najdowski et al. 2018), and public transportation (Neef et al. 1978) skills. Furthermore, behavioral strategies can address tolerance to medical appointments (Cox et al. 2017), improve behaviors such as wearing orthotics and hearing aids (Richling et al. 2011), and increase medication acceptance (Schiff et al. 2011). Moreover, there is behavior–analytic literature of developing effective sleep habits (Jin et al. 2013) and reducing problem behaviors (Kunnavatana et al. 2018).

Despite experimental literature addressing behavioral concerns that overlap in individuals with PMS and those diagnosed with ASD, no experimental or review literature exists that bridges these two diagnoses in terms of behavior-analytic treatments. This is concerning, particularly for parents and providers as a literature on behavior management and skill development strategies for PMS is sparse. Perhaps one reason for the dearth of PMS-specific literature in ABA is that individuals with PMS are often also diagnosed with ASD and, as such, additional research on the PMS population might seem redundant. It is possible researchers are assuming that the behavioral features being treated are due to the ASD, not the PMS, but specifying the PMS diagnosis in reporting is necessary as excluding the genetic diagnosis from publication and demographic reporting is problematic and may account for some of the variability in results (i.e. why one client does not respond to an otherwise effective treatment). However, there are behaviors in ASD that can be treated using, for example, differential reinforcement because they are assumed to be motivational deficits, whereas in PMS these same behaviors might be due in part to physical limitations, so withholding a reinforcer is (a) unethical and (b) ineffective. This difference necessitates additional experimental work to demonstrate that ABA-derived treatments in ASD can remain viable, safe, and ethical when applied to PMS. We offer the behavior analyst working with PMS clients the following suggested actions—though the list might not be exhaustive—when navigating treatment options to factor in necessary adjustments to accommodate the disorder.

The Professional and Ethical Compliance Code for Behavior Analysts states in Code 3.02 the behavior analyst’s obligation to recommend a medical consultation if there is a possibility that behavior is affected by biological or medical variables (Behavior Analyst Certification Board 2014). Consequently, behavior analysts should first contact the client’s medical team regarding current medication, diagnoses, and how to plan for mutually beneficial coordination of services. Request and document current medication, their intended effects, and the possible side effects of the medication when planning intervention (see Table 2 as a reference list for documented medication improvements and side effects). Track behavior data with respect to medication changes and consider how long medication can take to be effective and how long it can take to wash out. Document medical issues (e.g. low muscle tone) and understand their expression. Discuss how the medical team can support behavioral intervention (e.g. medical treatments regarding constipation) and find out what would make medical/dental appointments easier for physicians through behavior–analytic work (e.g. increase tolerance of medical equipment during examinations or procedures).

Table 2.

Reference of common medication in PMS and their effects.

Medication	Study	Improvements	Side effects
Hormones
Intranasal insulin	Schmidt et al. (2009)	Fine and gross motor ability, independence in education, cognitive functions, nonverbal communication, and autonomous functioning	General loss of interest, sensitivity to touch, changes in balance, and nosebleed
	Zwanenburg et al. (2016)	Participants who were older than three-years-old displayed significant social and cognitive improvements. Increases in developmental functioning were also observed; however, results were not significant	Irritation of the nasal area and nosebleeds
Insulin-like growth factor-1	Kolevzon et al. (2014b)	Restrictive behaviors and social impairments	No serious side effects; however, while not serious, more side effects were reported during the IGF-1 phase
Antipsychotics
Risperidone1 (aka Risperdal)	Pasini et al. (2010) Case report	Aggressive behavior, insomnia, anxiety, or psychomotor agitation	Psychomotor agitation, insomnia, and anxiety
Quetiapine (aka Seroquel)	Messias et al. (2013) Case report	Sleep/wake cycles, psychotic symptoms, independence, speech, and affect	Continued symptoms of depression
Lithium	Serret et al. (2015) Case report	Reversal of clinical regression, stabilized behavioral symptoms, and recovered pre-regression levels of functioning	No significant side effects
	Darville et al. (2016) Case report	Adaptive behavior improved to near pre-regression states	None discussed
Lithium and Risperidone	Ballesteros et al. (2017) Case report	Socio-functional stability	None discussed2
Lithium and Olanzapine (aka Zyprexa)	Egger et al. (2017) Case report	Affect, mood, and behavior	None discussed
Drug Combinations
Anti-psychotics and Anti-convulsants
Carbamazepine and Aripiprazole	Vucurovic et al. (2012) Case report	Mood	Hyperactivity continued
Pipamperone and Carbamazepine	Verhoeven et al. (2013) Case report	Acceptable behavior and mood	None discussed
Anti-convulsant and Anti-depressants
Valproic Acid and Nortriptyline	Verhoeven et al. (2012) Case report	Behavior and mood	None discussed
Carbamazepine and Paroxetine	Verhoeven et al. (2012) Case report	Full remission of psychiatric symptoms	None discussed
Anti-psychotics, Stimulants, and Benzodiazepines
	Denayer et al. (2012) Case report		Possible overdose and skill regression
Hormones, Anti-psychotics, and Anti-convulsants
Levothyroxine, Pipamperone, and Lamotrigine	Egger et al. (2016) Case report	Behavior and mood	None discussed
Valproic acid and Quetiapine	Egger et al. (2016) Case report	Behavior and mood	None discussed
Quetiapine	Egger et al. (2016) Case report	Functioning	None discussed

Note. Table 2 is provided as a reference for those working with clients taking specific medication or combinations. Table 2 is meant to provide practitioners insight into what might occur with medication use. Medications retained from articles found in a systematic literature review displayed in chronological order by type of medication (Schroeder, 2018).

¹ Improvements and side effects were dose dependent.

² Lithium was originally used alone; however, improvements and side effects listed are regarding the combination of Lithium and Risperidone.

Understand that clients with PMS might be absent frequently due to illness, medical complications, or medical appointments. Be sure to indicate days where illness is suspected or confirmed when recording data as progress will be affected. Determine how illness will affect consistency of treatment and whether and how secondary plans may need to be implemented. For example, when healthy, the treatment team should run 100% of programming; however, if ill, modified priority programs should be preplanned to continue (e.g. communication, toileting, eating) as repetition is particularly important for those with PMS to continue progress and avoid regression. Balance and adjust requirements according to difficulty and illness severity.

Similarly, practitioners working primarily with clients diagnosed with ASD may anticipate seeing behavioral improvement within a particular timeframe; clients with PMS may require a longer intervention period to show similar progress, so practitioners should be careful not to discontinue or adjust programming too quickly. Two aspects should be considered: time until progress is seen and size of steps. Those with PMS might require many more sessions, and trials per session, to achieve the same progress as someone diagnosed with ASD. Practitioners might be quick to modify a program as the target could appear ineffective when the program only needed more repetitions. To show progress, break targets into small steps. For example, in a brushing teeth program, create a target for taking the cap off the toothpaste. Then combine response and stimulus prompts for each step (e.g. partial physical prompt, enlarge the toothpaste’s cap with tape, and highlight the cap red) tapering slowly down (e.g. gestural prompt, enlarge the toothpaste’s cap with tape, and highlight the cap red). Due to slow progress, it will be difficult to determine when a program needs to be modified. To help make these determinations, confirm prior to implementation that targets are broken into the smallest steps necessary and thoughtful prompts are arranged. Prior to modifying a program, ensure practitioners are using highly preferred reinforcers and treatment integrity is acceptable.

Finally, buy-in and continual communication with caretakers is imperative. As has been described, repetition is particularly important for those with PMS. It is essential that priority programs (e.g. communication, toileting, eating) be consistently run at home. Discuss the importance of continued work at home. Modify key programs to work for the home environment’s routine in coordination with caretakers to ensure follow through. Daily communication and weekly reports are recommended. Daily communication should include discussion regarding illness, perceived pain, medication changes, dose changes, missed medication, diet, problem behaviors, toileting, and sleep. Weekly reports should include an incident tracker highlighting the preceding that can be shared with the client’s physician. In addition, discussion on changes at home, changes in behavior, progress noticed, and regression observed should also be addressed.

Conclusion

No studies or reviews are available to guide behavior analysts on how to effectively work with individuals in the PMS community. Though behavior analysis has a history of producing change in many of the behavioral excesses and deficit areas identified in PMS, caution is provided in starting with a PMS client prior to seeking proper supervision or ensuring ethical obligations are met. For example, our technology would need to be adjusted through collaboration with medical professionals and families to ensure we continue to individualize treatment to the specifics of each person affected by PMS. Additionally, information on PMS can be found through the Phelan–McDermid Syndrome Foundation at www.pmsf.org regarding conferences and how to gain further knowledge on the population. While the purpose of the current paper was to highlight how medical concerns might affect behavioral issues and treatment gains in PMS, similar analyses for other developmental disabilities should be explored to increase ABA’s effectiveness and expand services.

Disclosure Statement

The authors declare no conflict of interest.

Funding

The authors confirm that there was no funding received regarding any aspect of this investigation.