Family Impact of 1P36 Deletion Syndrome

Home , 1p36 deletion syndrome

Family Impact of 1p36 Deletion Syndrome

A thesis submitted to the

Graduate School

of the University of Cincinnati

in partial fulfillment of the

requirements for the degree of

Master of Science

In the Genetic Counseling Program

of the College of Medicine

April 2016

Rania Sheikh

B.S. James Madison University 2014

Committee Chair: Robert Hopkin, MD

Research Advisory Committee: Ashley Brazil, M.S., L.G.C.

Valentina Pilipenko, Ph.D

ABSTRACT

Background: 1p36 deletion syndrome is the most common microdeletion syndrome affecting approximately 1 in 5,000-10,000 newborns. However, little is known about the impact felt by caregivers of individuals with 1p36 deletion syndrome and related caregiver needs. This study assessed the family impact and provides a resource for individuals both within and outside the healthcare field. Methods: A questionnaire consisting of the Pediatric Quality of LifeTM

(PedsQL) family impact module, demographics, and phenotype assessment was distributed to caregivers at the annual 1p36 Deletion Support and Awareness conference. The PedsQLTM family impact module was scored out of 100, with lower scores indicating higher impact.

Results: Of 56 participants that completed a survey, the mean total impact score of the

PedsQLTM family impact module was 51.8. The individual caregiver dimension scores for parent functioning were 56.4 (physical functioning), 54.3 (emotional functioning), 47.4 (social functioning), 57.2 (cognitive functioning), 54.2 (problems with communication), and 43.3

(worry). Scores for family functioning were 33.9 (daily activities) and 59.5 (family relationships). Caregivers who reported that their child had behavioral challenges such as excessive friendliness and/or aggressive tendencies were found to experience significantly higher impact in several of the PedsQLTM family impact module domains. Conclusions: Our results suggest that behavioral problems were the biggest challenge for many caregivers. Healthcare providers, including genetic counselors and geneticists, should consider addressing the family impact of having a child with 1p36 deletion syndrome and related behavioral challenges.

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ACKNOWLEDGMENTS

I would like to acknowledge the hard work, guidance, and continued support I received from my research committee, Ashley Brazil, MS, LCG, Robert Hopkin, MD, and Valentina Pilipenko,

Ph.D. I would also like to thanks the 1p36 Deletion Support and Awareness (1p36 DSA) organization and Cincinnati Children’s Hospital Division of Human Genetics for funding my travels to the annual 1p36 DSA conference. I would like to thank Tod Oliver for providing his unpublished data titled “1p36 Quality of Life Survey” and Kellizabeth Warsinske for her contribution to this project in the preparations of the final manuscript. Finally, I would like to extend a special thank you to the caregivers that participated in our study for their time, effort, and willingness to contribute to research on 1p36 deletion syndrome.

TABLE OF CONTENTS

Introduction ...... 1

Methods ...... 1

Results ...... 3

Discussion...... 5

Limitations and Conclusions ...... 7

Tables ...... 9

References ...... 15

LIST OF TABLES

Table I: Demographic Characteristics Caregivers

Table II: Demographic Characteristics of Individuals with 1p36 Deletion Syndrome

Table III: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules in Caregivers of Individuals with 1p36 Deletion Syndrome

Table IV: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules: Comparisons across 1p36 deletion syndrome Caregivers and REACH Sample

Table V: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules in Caregivers of Individuals with 1p36 Deletion Syndrome Correlating to Specific Phenotypic Characteristics

Table VI: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules comparisons between maternal, paternal, and other Caregivers of Individuals with 1p36 Deletion Syndrome

INTRODUCTION

One of the most common terminal deletion syndromes, 1p36 deletion syndrome, otherwise known as monosomy 1p36, has an estimated incidence of 1 in 5000 births [Heilstedt et al., 2003; Shaffer & Lupiski, 2000]. Individuals with 1p36 deletion syndrome have multiple congenital anomalies and cognitive delays [Shapira et al. 1997]. Some of the characteristics patients with 1p36 deletion syndrome have are distinct craniofacial features, behavioral, vision and hearing problems, varying levels of intellectual disability and developmental delay, and other health concerns involving the cardiovascular, gastrointestinal, neurological, and muscular systems [Battaglia, 2005; Brazil et al., 2014 Gajecka et al., 2007; Heilstedt et al. 2003; Vieira et al. 2011].

Several studies have delineated the genotype and phenotype of 1p36 deletion syndrome in individuals from infancy to adulthood; however, data on the family impact of a diagnosis of this syndrome is currently unavailable. Research indicates that caregivers are prone to psychological and emotional distress if a child in their family has congenital health complications [Hodapp et al., 1997; Murphey et al., 2007] This study will serve to describe the impact 1p36 deletion syndrome has on families as reported by different caregivers, in the hopes that acknowledging, addressing, and discussing these impacts can lead to a healthier mental and physical status in the caregiver. A healthier caregiver could thereby provide an overall better quality care for the patient.

METHODS

This was a cross-sectional descriptive study of a cohort of caregivers of individuals with

1p36 deletion syndrome designed to assess the family impact of having a child with 1p36.

Participants were recruited through the 2015 1p36 Deletion Support & Awareness annual conference, held in Orlando, FL. Caregivers completed the surveys in person at the conference

1 and returned it to a member of the research team. Participants must be related to or the legal guardian of the person with 1p36 deletion syndrome and the person with 1p36 deletion syndrome must have had a diagnosis confirmed by genetic testing. Paid caregivers were excluded. Prior to data collection, this study was reviewed and approved by the Institutional Review Board for

Human Subject Research at Cincinnati Children’s Hospital Medical Center (IRB#2015-2532:).

The questionnaire consisted of three components: The Pediatric Quality of LifeTM

(PedsQL TM) Family Impact Module, a demographics sheet, and a phenotype assessment sheet.

The PedsQLTM family Impact Module is a tool that measures caregivers’ self-reported overall well-being in different dimensions of everyday life. It has 36 items separated into eight sections.

The first six measure an individual caregiver’s functioning, and the last two measure family functioning. Together, the eight dimensions examine problems with the caregiver’s physical functioning, emotional functioning, social functioning, cognitive functioning, communication, worry, and the family’s daily activities and family relationships. PedsQLTM has a measurement scale that generates a certain score dependent on the participants’ responses to the 5-point Likert scale questions. Preliminary reliability and validity was established for the PedsQLTM Family

Impact Module’s in a study by Varni et al comparing the family impact of children with complex health care needs who resided with their families vs. residing in long term care facilities. [Varni et al., 2004]. The total score is the sum of all 36 items in the tool, divided by the number of items answered. Scores from all the participants are transformed linearly to a 0-100 scale, with a higher score indicating better functioning.

All survey responses were collected in person. A grandparent and parent of a deceased patient with 1p36 deletion syndrome completed separate questionnaires; these completed responses were included in the final analysis. Summary statistics were produced using JMP

12.0.1 (SAS, Cary, NC). Means and standard deviations were included for continuous variables, and frequencies were included for categorical variables. Appropriate statistical methods

(ANOVA, Fisher’s exact test, or t-test) were used to examine for statistically significant differences between groups. Results were judged statistically significant at the nominal level

(p<0.05).

RESULTS

A total of 56 caregivers of individuals with 1p36 deletion syndrome were included in the study. Of those, 55 participants completed all three components (PedsQL TM, demographics, and phenotype assessment) and 1 completed only the PedsQL TM section. The majority of the respondents were biological mothers (69.6%) and self-identified as white (91.1%). Distribution of demographics is shown in Table I. Table II demonstrates medical co-morbidities of patients with 1p36 as reported by their caregivers. Over 80% of patients were reported to have fine motor delay, gross motor delay and/or hypotonia at birth.

Table III demonstrates mean scores of the PedsQL TM 2.0 Family Impact Module, and includes the total impact score (51.8) and the individual dimension scores the total impact score consists of. The eight sections separately measured problems with physical (56.4), emotional

(54.3), social (47.4), and cognitive functioning (57.2), and problems with communication (54.2), worry (43.3), daily activities (33.9), and family relationships (59.5) as reported by the caregivers on a 0-4 Likert scale. The total score is the sum of all 36 questions in the tool, divided by the number of items answered. The scores from each participant are transformed linearly to a 0-100 scale, with a higher score indicating better functioning [Varni et al., 2004]. For individual sections, original scores were out of the specific number of questions for each section. For simplicity and consistency with the final overall score, individual total scores were converted

3 into means out of a 100. Table IV compares our results to Varni et al.’s (2004) aggregate

PedsQLTM Family Impact Module data. When compared to the cohort from Varni et al., our cohort of caregivers had lower functioning in all dimensions except communication and physical functioning.

Table V compares the caregivers’ total impact scores and individual dimension scores to phenotypic characteristics of children with 1p36 deletion. Specific phenotypic characteristics and medical comorbidities were included in the survey based on published literature delineating 1p36 deletion syndrome [Battaglia, 2005; Brazil et al., 2014 Gajecka et al., 2007; Heilstedt et al.,

2003; Vieira et al. 201]. Caregivers selected medical co-morbidities their children had out of the list supplied in the survey at the conference. The calculated individual dimension and total impact scores were then compared to each of the medical and neuro-behavioral co-morbidities that were self-reported by the caregiver as a phenotype of the individual with 1p36 deletion syndrome. Table V demonstrates potential correlations between specific health complication in children with 1p36 deletion syndrome, and the resulting impact on the caregivers and family dynamics. Of note, caregivers reported significantly worse cognitive and emotional functioning, family relations and daily activities scores as well as worse total impact scores if they reported their child as being excessively friendly. Additionally, caregivers who reported that their children had altered behavior (temper outburst, self-injuring behavior, violent physical activity etc…) also had significantly worse scores in social and emotional functioning, communication, family relationships, and daily activities scores, as well as lower total impact scores.

Table VI compares individual dimension scores and total impact score among different types of caregiver. Types of caregivers compared include maternal, paternal and other (non- paternal/maternal caregiver). Maternal caregivers show lower scores in all dimensions except

4 communication, and in total impact score in comparison to paternal caregivers. Other caregivers had lower totals than both paternal and maternal caregivers in four dimensions (physical, social, emotional and cognitive functioning), and in total impact score. In the remaining four dimensions, other caregivers scored lower than paternal caregivers but not maternal caregivers in two dimensions (daily activities and worry totals), and higher than both paternal and maternal caregivers in the other two dimensions (family relationships and communication totals).

DISCUSSION

The aim of this study was to describe the impact 1p36 deletion syndrome has on families.

Families of children with chronic health conditions are known to be significantly impacted psychologically and emotionally by the complex needs of their special needs family member

[Hodapp et al., 1997; Murphey et al., 2004; Varni et al., 2004]. Family-centered care has often been suggested to address the impact on the whole family unit. Evidence shows that family- centered care leads to greater satisfaction with overall services and is thought to be a recognized method of caring for children with chronic conditions such as 1p36 deletion syndrome [Law et al., 2003; Ygge et al., 2005]. By describing the family impact, we identify aspects of caregivers’ lives that may need additional support to incorporate into family-centered care, and provide anticipatory guidance to future or new caregiver.

Varni et al. (2004) studied the family impact of having medically fragile children with complex chronic health conditions using the PedsQL TM and found higher total impact scores and higher individual scores in nearly every dimension than in our study population. The dimensions of cognitive functioning and family relationships specifically were significantly lower in our caregiver population. This difference in impact may be due to behavioral challenges present in the 1p36 deletion syndrome population that may be absent in chronically ill children.

Many studies have shown that behavioral concerns in a child with developmental disabilities are a challenge [Reilly et al. 2015; Varni et al., 2004]. Reilly et al. found that parents of individuals with Fragile X syndrome reported aggressive behavior as a significant challenge and parents of children with William’s syndrome most often reported their child’s excessive sociability as a significant challenge. Almost 39% of caregivers of children with 1p36 deletion syndrome reported either not having sufficient skills to manage the behavior of their child, or were unsure if they do have those skills in previously unpublished data [Tod Oliver; Unpublished

Data, 2015]. Among our caregivers, 44% reported that their child had excessively friendly behavior and 42% reported their child had altered behavior described as episodes of temper outburst, self-injuring behavior or violent physical activity. 25% of our caregivers reported that their child had both. In this study, we found that caregivers who reported that their 1p36 child had behavioral concerns (excessive friendliness and/or altered behavior) correlated with lower scores in several dimensions and lower total impact scores (lower scores indicate higher family impact). Our findings illustrate behavioral problems are one of the most challenging aspects and sources of stress for parents/caregivers of a child with a developmental disability.

Previous literature indicated that mothers are at a higher risk for facing difficulties regarding psychosocial adjustment when their children have a chronic physical disorder

[Wallander & Varni, 1998]. This could be due to common coping strategies used by mothers including focusing more on a child than on other life tasks which may be more emotionally taxing [Alam et al., 2012]. Such strategies may vary between mothers and fathers partly due to predetermined social norms. Mothers of children with autism were found to express more emotionally-focused mechanisms for coping with stress, and to have an overall higher level of stress in comparison to fathers [Dabrowska & Pisula et al., 2010]. Although not statistically

6 significant, mothers in our study reported lower average functioning in all dimensions, except communication, when compared to fathers; this further supports how differences in coping styles can affect the overall wellbeing between parents.

Family relationships and communication among family members are well known areas of stress for families with children with chronic medical problems. For example, siblings of children with Rhett and Down syndrome experienced some advantages among family relationships, tolerance, and communication. However, a majority of non-affected siblings were also noted to have disadvantages including less time to spend with their parents, exposure to financial and emotional stress, and feeling burdened to help with their sibling with Rhett or

Down syndrome [Mulroy et al., 2008]. Similarly, a separate study found that families of children with Prader Willi syndrome face issues in communication and family functioning, an increase in number of conflicts, and have poorer perceived quality of life, with over 90% of the siblings in the study showing variable signs of post-traumatic stress disorder [Mazaheri et al. 2013]. Finally,

McStay et al. found that behavioral aspects of a diagnosis such as hyperactivity and lack of social skills cause more stress in families with children with autism spectrum disorder than severity of a diagnosis or quality of life [McStay et al., 2013]. Caregivers whose child with 1p36 deletion syndrome had either excessive friendliness, altered behavior, or both reported significantly lower family relationships scores. Previous data indicated that over 50% of caregivers of children with 1p36 deletion syndrome report not enjoying social outings as much as they did before having a child with 1p36 deletion syndrome [Tod Oliver; Unpublished Data,

2015]. Therefore, having a child with special needs may pose restrictions to overall family dynamics.

LIMITATIONS AND CONCLUSION

Certain limitations should be taken into consideration when interpreting the results of this study. All study subjects were recruited at the Annual 1p36 Deletion Support and Awareness

(1p36 DSA) conference. This may lead to certain biases when completing the surveys and limit the generalizability of the study to families who have the resources to attend conferences.

Additionally, medical data and diagnoses are self-reported; patients’ medical records and genetic testing results were not obtained.

The findings of our study highlight the involvement of behavioral challenges as a major cause of distress in families of children with 1p36 deletion syndrome. In a similar study to ours,

Reilly et al. suggests replacing parental reports of a child’s behavioral challenges with professional assessments using standardized measures [Reilly et al., 2015]. This may be useful in both further delineating the behavioral challenges seen in children with 1p36 deletion syndrome, and in providing more targeted support to caregivers and other family members. Additional services such as family counseling for caregivers/siblings, targeted psycho-educational and emotional supports can also be recommended [Reilly et al., 2015]. Lastly, based on out data, healthcare professionals such as genetic counselors and geneticists can provide psychosocial support and anticipatory guidance for families on potential stressors in their family.

TABLES

Table I: Demographic Characteristics Caregivers Characteristic N (%)

Gender Male 11 (19.6) Female 44 (78.6) Not Reported 1 (1.8)

Type of Caregiver Mother 39 (69.6) Father 9 (16.1) Other 7 (12.5) Not Reported 1 (1.8)

Race White 51 (91.1) Other 4 (7.1) Not Reported 1 (1.8)

Family Income < $40 K 13 (23.2) ≥ $40 K but < $80 K 14 (25) ≥ $80 K but < $120 K 15 (26.8) > $120 K 13 (23.2) Not Reported 1 (1.8)

Highest Education Level High School Graduate or less 7 (12.5) Some College or Certification Course 14 (25) College Graduate 24 (42.8) Graduate or Professional Degree 10 (17.9) Not Reported 1 (1.8)

Marital Status Married 39 (69.6) Living with Someone 6 (10.7) Other 10 (17.9) Not Reported 1 (1.8)

Table II: Demographic Characteristics of Individuals with 1p36 Deletion Syndrome Characteristic N (%)

Age 0-5 22 (39.3) >5 31 (55.3) Not Reported 3 (5.4)

Gender Female 30 (53.6) Male 25 (44.6) Not Reported 1 (1.8)

Weight Normal 21 (37.5) Overweight 11 (19.6) Underweight 21 (37.5) Not Reported 3 (5.4)

Medical Co-morbidities Cleft Lip/Palate 6 (11) Born With Cardiomyopathy 9 (16) Congenital Heart Defects 17 (31) Born with Hypotonia 44( 80) Brain Malformations 19 (35) Constipation 36 (65) Diarrhea 23 (42) Seizures 23 (44) Hearing Impairment 18 (33) Vision Problems 27 (49) Hypothyroidism 6 (11) Cardiomyopathy in the last month 7 (13) Hypotonia in the last month 24 (44) Fine Motor Delay 48 (87) Gross Motor Delay 47 (85) Poor Coordination 40 (73) Unable to sit independently 19 (35) Unable to Walk Independently 23 (42) Unable to Verbally Communicate 37 (67) Unable to Feed physically 25 (45) G/NG-tube 10 (18) Needs Assistance Going to the 35 (64) Bathroom

Neuro-Behavioral Co-morbidities Excessive Friendliness 24 (44) Altered/Aggressive Behavior 23 (42) Unable to Communicate Using 27 (49) Assisted Tech/Sign Language Delayed Speech 43 (78) Cognitive Delay 42 (76)

Table III: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules in Caregivers of Individuals with 1p36 Deletion Syndrome Scale N Mean (SD)

Total Impact Score 56 51.8 (15.7)

Parent Functioning

Physical Functioning 56 56.4 (20.44) Emotional Functioning 56 54.3 (20) Social Functioning 56 47.4 (22.7) Cognitive Functioning 56 57.2 (24) Communication 56 54.2 (22) Worry 56 43.3 (20.9)

Family Functioning

Daily Activities 56 33.9 (25.3) Family Relationships 56 59.5 (24.4) Note: Higher values denote better functioning

Table IV: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules: Comparisons across 1p36 deletion syndrome Caregivers and REACH* Sample REACH SAMPLE 1P36 DELETION SYNDROME CAREGIVERS

Scale N Mean SD N Mean SD Difference P-value Total Impact Score 11 62.49 17.26 56 51.8 15.7 10.69 0.072 Physical 11 53.03 22.83 56 56.4 20.4 -3.37 0.65 Functioning Emotional 11 64.48 26.59 56 54.3 20 10.18 0.26 Functioning Social Functioning 11 61.93 25.99 56 47.4 22.7 14.53 0.11 Cognitive 11 74.09 18.95 56 57.2 24 16.89 0.02 Functioning Communication 11 52.15 24.67 56 54.2 22 -2.05 0.8 Worry 11 56.82 25.52 56 43.3 20.9 13.52 0.14 Daily Activities 11 51.89 31.48 56 33.9 25.3 17.99 0.11 Family 11 78.95 27.62 56 59.5 24.4 19.45 0.042 Relationships *REACH = Aggregate PedsQL TM Family Impact Module Data collected by Varni et al. (2004) on families of “medically fragile children with complex chronic health conditions” who lived at home with familial caregivers

Table V: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules in Caregivers of Individuals with 1p36 Deletion Syndrome Correlating to Specific Phenotypic Characteristics

Scale Phenotype Y/N N Mean P-value Cognitive cardiomyopathy N 46 54.57 0.018 Functioning Total Y 9 72.22 Congenital Heart Defects N 38 53.52 0.038 Y 17 66.47 G/NG-tube N 45 54.67 0.036 Y 10 70.00 Excessive Friendliness N 31 66.45 0.002 Y 24 45.83 Communication Anorectal/gastrointestinal N 52 53.05 0.047 Total malformation Y 3 80.56 Altered behavior N 32 59.90 0.033 Y 23 47.10 Worry Total Cognitive Delay N 13 55.38 0.044 Y 42 39.88 Daily Activities Brain Malformations N 36 39.81 0.024 Total Y 19 23.68 Altered behavior N 32 41.15 0.014 Y 23 24.64 Excessive friendliness N 31 41.94 0.010 Y 24 24.31 Family Walk Independently N 32 53.75 0.031 Relationships Y 23 67.39 Total Altered behavior N 32 68.44 0.002 Y 23 46.96 Excessive friendliness N 31 65.65 0.042 Y 24 51.46 Emotional CL/P N 49 52.76 0.005 Functioning Total Y 6 67.50 cardiomyopathy N 46 52.39 0.044 Y 9 64.44 Diarrhea N 32 59.38 0.041 Y 23 47.39 Unable to walk N 32 49.69 0.050 Independently Y 23 60.87 Altered behavior N 32 59.22 0.040 Y 23 47.61 Excessive friendliness N 31 59.35 0.044 Y 24 47.92 Social Functioning Cognitive Delay N 13 57.69 0.029 Total Y 42 44.79 Altered behavior N 32 55.08 0.003 Y 23 37.77 Total Impact Altered behavior N 32 57.38 0.002 Score Y 23 44.41 Excessive friendliness N 31 56.77 0.010 Y 24 45.75 Cognitive Delay N 13 58.07 0.046 Y 42 50.07

Table VI: Scale Descriptives of the PedsQL TM 2.0 Family Impact Modules comparisons between maternal, paternal, and other Caregivers of Individuals with 1p36 Deletion Syndrome Scale Relationship N Mean SD P-Value Physical Functioning Father 9 62.04 9.42 0.6456 Total Mother 39 55.77 20.02 Other 7 52.98 33.31 Emotional Father 9 55.00 16.39 0.9765 Functioning Total Mother 39 54.49 20.19 Other 7 52.86 27.06 Daily Activities Total Father 9 35.19 20.32 0.9916 Mother 39 33.97 26.03 Other 7 34.52 31.34 Communication Total Father 9 49.07 24.81 0.4523 Mother 39 54.27 21.28 Other 7 63.10 23.00 Social Functioning Father 9 50.00 20.01 0.9468 Total Mother 39 47.60 22.97 Other 7 46.43 27.21 Cognitive Functioning Father 9 67.22 25.14 0.2574 Total Mother 39 57.05 22.73 Other 7 47.14 29.84 Worry Total Father 9 47.78 20.78 0.7714 Mother 39 42.31 20.86 Other 7 45.00 24.15 Family Relationships Father 9 60.56 21.57 0.8367 Total Mother 39 58.33 23.49 Other 7 64.29 35.99 Total Impact Score Father 9 54.94 8.25 0.8299

Mother 39 51.41 16.11 Other 7 51.19 22.07

REFRENCES

Alam, R., Barrera, M., D'agostino, N., Nicholas, D. B., & Schneiderman, G. (2012). Bereavement Experiences of Mothers and Fathers Over Time After the Death of a Child Due to Cancer. Death Studies, 36(1), 1-22. Battaglia, A. (2005). Del 1p36 syndrome: A newly emerging clinical entity. Brain and Development, 27(5), 358-361. Brazil, A., Stanford, K., Smolarek, T., & Hopkin, R. (2014). Delineating the phenotype of 1p36 deletion in adolescents and adults. Am. J. Med. Genet. American Journal of Medical Genetics Part A, 164(10), 2496-2503. Dabrowska, A., & Pisula, E. (2010). Parenting stress and coping styles in mothers and fathers of pre-school children with autism and Down syndrome. Journal of Intellectual Disability Research, 54(3), 266-280. Gajecka, M., Mackay, K. L., & Shaffer, L. G. (2007). Monosomy 1p36 deletion syndrome. Am. J. Med. Genet. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 145C(4), 346-356. Heilstedt, H., Ballif, B., Howard, L., Kashork, C., & Shaffer, L. (2003). Population data suggest that deletions of 1p36 are a relatively common chromosome abnormality. Clinical Genetics, 64(4), 310-316. Heilstedt, H. A., Ballif, B. C., Howard, L. A., Lewis, R. A., Stal, S., Kashork, C. D., . . . Shaffer, L. G. (2003). Physical Map of 1p36, Placement of Breakpoints in Monosomy 1p36, and Clinical Characterization of the Syndrome. The American Journal of Human Genetics, 72(5), 1200-1212. Law, M., Hanna, S., King, G., Hurley, P., King, S., Kertoy, M., & Rosenbaum, P. (2003). Factors affecting family-centred service delivery for children with disabilities. Child: Care, Health and Development, 29(5), 357-366. Mazaheri, M. M., Rae-Seebach, R. D., Preston, H. E., Schmidt, M., Kountz-Edwards, S., Field, N., . . . Packman, W. (2012). The impact of Prader-Willi syndrome on the family's quality of life and caregiving, and the unaffected siblings’ psychosocial adjustment. Journal of Intellectual Disability Research J Intellect Disabil Res, 57(9), 861-873. Mcstay, R. L., Dissanayake, C., Scheeren, A., Koot, H. M., & Begeer, S. (2013). Parenting stress and autism: The role of age, autism severity, quality of life and problem behaviour of children and adolescents with autism. Autism, 18(5), 502-510. Mulroy, S., Robertson, L., Aiberti, K., Leonard, H., & Bower, C. (2008). The impact of having a sibling with an intellectual disability: Parental perspectives in two disorders. Journal of Intellectual Disability Research J Intellect Disabil Res, 52(3), 216-229. Murphy, N. A., Christian, B., Caplin, D. A., & Young, P. C. (2007). The health of caregivers for children with disabilities: Caregiver perspectives. Child: Care, Health and Development Child Care Health Dev, 33(2), 180-187. Reilly, C., Murtagh, L., & Senior, J. (2015). The Impact on the Family of Four Neurogenetic Syndromes: A Comparative Study of Parental Views. Journal of Genetic Counseling J Genet Counsel, 24(5), 851-861. Shaffer, L. G., & Lupski, J. R. (2000). Molecular Mechanisms for Constitutional Chromosomal Rearrangements in Humans. Annu. Rev. Genet. Annual Review of Genetics, 34(1), 297- 329. Shapira, S. K., Mccaskill, C., Northrup, H., Spikes, A. S., Elder, F., Sutton, V. R., . . . Shaffer, L. G. (1997). Chromosome 1p36 Deletions: The Clinical Phenotype and Molecular

Characterization of a Common Newly Delineated Syndrome. The American Journal of Human Genetics, 61(3), 642-650. Varni, J. W., Sherman, S. A., Burwinkle, T. M., Dickinson, P. E., & Dixon, P. (2004). The PedsQLTM Family Impact Module: Preliminary reliability and validity. Health and Quality of Life OUtcomes, 2(55). Vieira, G. H., Rodriguez, J. D., Boy, R., Paiva, I. S., Dupont, B. R., Moretti-Ferreira, D., & Srivastava, A. K. (2011). Differential diagnosis of Smith-Magenis syndrome: 1p36 deletion syndrome. Am. J. Med. Genet. American Journal of Medical Genetics Part A, 155(5), 988-992. Wallander, J. L., & Varni, J. W. (1998). Effects of Pediatric Chronic Physical Disorders on Child and Family Adjustment. J Child Psychol & Psychiat Journal of Child Psychology and Psychiatry, 39(1), 29-46.