INTRODUCTION
Genomic disorders are increasingly being recognized as etiologic factors in a variety of neurodevelopmental disorders,1 2
One such genomic disorder, known as 16p11.2 deletion syndrome, includes loss of genetic material on a segment of chromosome 16.3 4 3 4–11 3 , 5 , 7–9 5 , 7–9 7 8 , 10 7–9 , 11 4 , 8 , 11 , 12 6 , 11 , 13 8 , 14 4 , 12 4 5 , 7 15 16 7–9
Current research in neuroscience and child development supports the critical role of early intervention services for children with neurodevelopmental concerns.17 18
Although 16p11.2 deletion syndrome is relatively new to the literature, it is becoming recognized as 1 of the most prevalent genetic disorders affecting children with developmental delays and/or autism.8 physical therapy services, through the Birth to Three System, for 1 child with 16p11.2 deletion syndrome.
CASE DESCRIPTION: PATIENT HISTORY AND SYSTEMS REVIEW
The child was referred to the Birth to Three System by his foster mother because of motor concerns at 3 months of age. History included birth at 32 weeks' gestation, birth weight of 3 lb 14 oz, tracheomalacia, laryngomalacia, gastroesophageal reflux disease, apnea spells, and referral for genetic testing. Familial history included unspecified genetic disorders and cognitive impairments in the child's biological mother and half-brother. He was discharged to foster care at 3 weeks of age, and remained with the same foster mother until being adopted by her. During 2¾ years of service, he exhibited numerous medical complications as noted in Table 1 .
TABLE 1: Medical Diagnosis Timeline
An initial systems review at 3 months of age included impairments mainly in the neuromuscular (5C) practice pattern as outlined in the Guide to Physical Therapist Practice,19
At 13 months of age, the initiation and subsequent escalation of maladaptive behaviors affected learning and interventions. The annual assessment by a PT and occupational therapist (OT) at 14 months of age revealed decreased rib cage mobility with sporadic use of accessory muscles for breathing, improvement in cardiopulmonary status during functional activities, normalized muscle tone with decreased torticollis pattern, feeding and regulation concerns, motor function and skill improvements, and overall developmental delay. Seizure disorder was diagnosed at 15 months of age. The child suffered a significant setback at 21 months of age after adrenal shock and hypoglycemic coma with resultant multiorgan failure, generalized brain edema, aspiration, and subsequent G-tube placement. Feeding and motor skills were greatly affected; the child demonstrated limited ability for oral feedings, overall hypertonicity, considerably increased left torticollis, lateral trunk flexion posture and active movement pattern, slightly decreased range of motion in the left sternocleidomastoid muscle, posturing with disuse of the right hand, decreased coordination, and balance. Eventually, motor recovery was achieved with return to previous motor baseline.
Fluctuating blood glucose levels persisted until growth hormone deficiency was diagnosed at age 25 months. During this period, concurrent with overall motor progression was deterioration in behavioral and communication areas, necessitating assessment by a speech pathologist. Autism evaluation at 24 months of age determined that he did not meet criteria for autism spectrum disorder. Annual assessment at 26 months of age revealed significant communication delays with good improvements in motor skills and functional activities. Assessment results at 33 months of age continued to show significant developmental delay most notably in the communication area. Feeding, mobility, and functional motor skills were greatly improved, as was respiratory capacity for activities. Improvements in balance and symmetry were attained, although concerns were still present.
TESTS AND OUTCOME MEASURES
Table 2 provides a summary of tests and outcome measures used in assessments for this child. Body structures/function of the International Classification of Functioning, Disability and Health (ICF) were measured through anthropometric reports of height and weight; cardiopulmonary assessment, including heart/respiratory rate and oxygen saturation through pulse oximetry; and clinical evaluation of tone, range of motion, reflexes, and movement patterns.
TABLE 2-a: Tests and Outcome Measurements
TABLE 2-b: Tests and Outcome Measurements
Initially and annually, the child received a standardized assessment using the Battelle Developmental Inventory-2 (BDI-2),20 20 21 22 23 24
After brain insult at 21 months of age, a detailed motor reassessment included evaluation of tone, range, reflexes, movement patterns, cardiopulmonary status, and functional activities. Standardized motor skill assessment was performed using the Peabody Developmental Motor Scales 2 (PDMS-2)25 26
The Hawaii Early Learning Profile,27 18 28
INTERVENTIONS AND OUTCOMES
The IFSP outcomes and measurable steps are reported in Table 3 . Provision of services in the Birth to Three System follows a coaching model in which caregiver education and collaboration are the primary foci of interventions.18 29 30 , 31 32 , 33
Table 3: IFSP Outcomes and Measureable Steps
Initial weekly physical therapy interventions were focused on the mother's priorities and functional, participation-based outcomes such as “Decrease stiffness when held so body is relaxed during feedings” and “Reach/grasp toy to play when on belly.” Focus was on instruction of the mother in strategies to promote the reduction of tone especially in the rib cage and trunk, head in midline, and lengthening of the left side during everyday activities such as carrying, diaper changing, bathing, and feeding. Environmental modifications such as towel rolls in infant seats, toy placement, and room arrangements facilitated carry-through of these postures and movements. The first 6 months of intervention included improving the child's cardiopulmonary status and skills in prone to facilitate motor progression.34 2 saturation and response to activity, necessitated frequent physician contact, which led to reflux medication changes and referral for cardiac, pulmonary, and gastrointestinal follow-up.
During the next period (age 9–15 months), interventions continued to be influenced by medical complexities. Physical therapy continued on a weekly basis with monthly consultations by the OT. Interventions addressing body function/structures focused on improved breathing and endurance through direct handling, as well as parental instruction in rib cage mobility activities, lengthening of pectoral and neck regions, and movement with rotation to reduce stiffness. Therapist concerns regarding decreased rib cage mobility, respiratory rate, rib retraction, and accessory muscle breathing necessitated ongoing physician contact and facilitation of a consultation with a respiratory PT to ensure that these issues were being thoroughly addressed. At 13 months of age, the child began maladaptive behaviors including throwing his head backward and banging it when upset. Ongoing reassessments by the therapist and the family were necessary to problem-solve potential causes of these behaviors as influenced by 16p11.2 deletion syndrome, medical conditions, medication side effects, communication frustrations, or pain. Fleeting dyskinesias and subtle changes in alertness, documented by the PT, led to further neurological testing. At 15 months of age, a seizure disorder was diagnosed with subsequent behavior deterioration. Close observation and documentation (including video) of symptoms by the PT, careful review of literature on the seizure medication (Keppra) noting migraines as an infrequent side effect, and collaboration with the neurologist resulted in medication change and behavioral improvement.
Interventions addressing activity/participation limitations involved family instruction in behavioral/regulation strategies such as using preferred activities (music) during nonpreferred tasks (diaper change), identifying sensory activities such as bouncing and compression to improve regulation, and providing safety during outbursts without excessive attention to undesired behaviors. Motor interventions included the facilitation of functional activities such as belly crawling with proper weight shifting; lengthening of posterior neck musculature during bottle and diaper change; sitting or side-lying activities during play with weight shift/elongation on left and facilitation of shortening on right; and strengthening activities through weight bearing during play. Environmental modifications to facilitate carryover included procuring a therapeutic chair with slight recline and trunk supports for optimum positioning during eating and breathing treatments, which occurred up to 6 times per day; furniture rearrangement so that the child looked at the television with head in midline during breathing treatments; toy/food placement to encourage increased use of the left hand; and ordering a soft helmet to protect the child, yet encourage independent mobility.
During the second year (age 16–27 months), issues that affected service delivery included continued pulmonary difficulties with frequent steroid use, medication side effects, maladaptive behaviors, hypoglycemic coma and adrenal shock with fluctuating blood glucose levels, and eventual diagnosis of growth hormone deficiency. Behavioral issues escalated after the initiation of cortisol and growth hormones in attempt to regulate blood glucose. Again, close observation and documentation by the PT facilitated medication adjustments. In addition, the PT supported the family during this period by attending several medical visits to discuss concerns and solve problems, providing written observations that the mom used during a specialist visits, suggesting additional consultations that might be beneficial (for instance, pediatric ophthalmology to determine whether vision was contributing to head tilt), and sharing information on the various conditions affecting the child.
During this period, although the focus was still on coaching the family, services expanded to include increased intensity of OT and speech therapy to meet the child's complex medical, behavioral, and developmental needs. The PT continued weekly visits as the “primary provider”35 Table 3 ).
During the third year of service (28–36 months), motor quality and skills continued to be addressed; however, child/family priorities emphasized behavioral and communication needs. Supports used by the family and all interventionists included pictures for transitions and during daily routines; Picture Exchange Communication System36 Physical therapy interventions included carryover of these strategies, and continued to address overall motor needs and the fluctuating pattern of active shortening on the left side of trunk/neck, which was more apparent when the child was under medical stress. This pattern was frequently reinforced during play when reaching with the right hand (Figure 1 ). It was felt that he would benefit from constraint-induced movement therapy (CIMT),37
Fig. 1: Left lateral trunk flexion and torticollis pattern reinforced when reaching with the right hand. This figure is available in color in the article on the journal website (
www.pedpt.com ) and iPad.
The medical and behavioral complexities of this child affected the attainment of all outcomes. Achievements related to body functions/structures included decreased hypertonicity, cardiopulmonary improvements in endurance and respiratory capacity for activities, normalized range in rib cage and neck, improved use of left arm, and increased trunk/neck symmetry, although he continued to be influenced by intermittent active shortening on the left side during some activities. Outcomes achieved in the activities component of the ICF included the progression of motor skills and improved function in prone/supine up through walking, running, and jumping. Improvements in the participation component of the ICF were noted by attainment of IFSP outcomes such as increased independence, skill, and safety moving around home/community; active participation in daily routines such as bottle feeding, diaper change, bathing, sitting at the table for family meals, and dancing with siblings.
Contextual/environment factors of the ICF were addressed through modifications of the home environment, provision of multiple opportunities for practice of skills through naturally occurring daily activities/routines, as well as facilitation of the mother's ability to further her son's development. Instruction of the mother/siblings was accomplished through demonstration, active practice with feedback, and strategies written on weekly home visit notes. The mother also obtained therapist feedback by forwarding video clips of behaviors/activities that were concerning or celebratory. His mother reported the development of knowledge, skill, and comfort in integrating strategies throughout normally occurring daily activities. Early referral, at 26 months of age, was made to Special Education Services to facilitate transition from the Birth to Three System and encourage a school environment that would meet his needs at age 3 years. The therapist supported the family by scheduling and attending the transition meeting and school visits, arranging joint visits in the child's home with the school and Birth to Three team members, and supporting community visits that allowed interaction with same-aged children in preparation for school. Further details are found in Table 3 .
DISCUSSION
The purpose of this case report was to review the presentation, complicating factors, and delivery of services through the Birth to Three System, for a child with 16p11.2 deletion syndrome. This syndrome is a relatively new diagnosis with which PTs may not be familiar. Although direct causation from the effects of 16p11.2 deletion cannot be determined, it is theorized that this deletion played a significant role in this child's clinical presentation and progression. The varied manifestations of 16p11.2 deletion reported in literature included many of his presenting problems: developmental delay, components of autism, significant communication delay, maladaptive behaviors, feeding difficulties, seizure disorder, and hormone and insulin dysregulation.
Complicating factors included complex, unstable medical conditions, side effects from multiple medications, and significant maladaptive behaviors. Physical improvements over time were noted in cardiopulmonary status and endurance for activities, functional motor skills, and quality of movement. Additional improvements were noted in feeding abilities, interaction and responsiveness, increased communicative intent through pointing, sporadic eye contact, gestures, use of pictures, and beginning word use. Behaviors continued to fluctuate, potentially affected by the genetic condition, medical conditions, medication side effects, pain, sensory regulation, communication frustrations, and age.
The PTs' role included detailed observation and documentation of symptoms; the development of systems for collecting data on behavior, medication, and feeding issues; frequent collaboration with medical professionals; formal and informal written updates that the mother shared with other specialists; and development of a close relationship with the pediatrician's medical home office to facilitate information sharing, problem solving, referrals, and equipment ordering. In addition, literature searches on 16p11.2 deletion syndrome and the child's medical conditions, use of drug reference resources, email contact with the lead investigator of a large study on the deletion syndrome, and investigation of support groups, current research trials, and 16p11.2 deletion syndrome resources supported decision making and parent education. Continual problem solving was necessary to determine ways to embed activities into family routines and allow for frequent repetition of activities for learning to occur. It was also critical to have consistent opportunities for joint visits and collaboration among all team members, including the child's mother, to review information collected, problem-solve, prioritize immediate needs, discuss possible interventions, and ensure consistent transdisciplinary carry-through of strategies. Frequent review and reassessment of IFSP functional outcomes, as driven by the child's needs and family's priorities, dictated the services and frequencies necessary to address those outcomes.
Essential for the family and the child was ongoing support by the PT to facilitate the transition process to school. This included support during community activities; early completion of the transition meeting with the mother and multiple members of the Birth to Three and preschool teams; completion of several joint home visits with members of both teams for school evaluation and preschool staff education purposes; and ongoing verbal and written communication with preschool staff. Recommended practices crucial to supporting the child and the family during this transition encourage communication and relationship building between programs. It has been shown that PTs who implement practices that encourage communication, collaboration, and relationship building between Birth to Three and preschool programs have greater involvement in the transition process,38
A limitation of this case report is that the child was born at 32 weeks' gestation and prematurity is known to contribute to certain difficulties experienced by this child.39 40
When working with a child with 16p11.2 deletion syndrome, it is critical for PTs to be aware of the varied manifestations of this genetic disorder and the potential effect on the health and development of the child. Close attention to presenting signs and symptoms, including medical and behavioral issues, as well as concerns in areas outside the scope of physical therapy practice may necessitate referral to and involvement of additional practitioners. Focus on caregiver instruction and education to accomplish family-driven, functional outcomes, as well as implementation of environmental modifications will increase carryover and allow the greatest potential for success. Advanced problem solving and clinical decision making, ongoing assessment, and collaboration are required when working with a child with 16p11.2 deletion syndrome to comprehensively support the family in meeting the child's medical, behavioral, and developmental needs.
ACKNOWLEDGMENTS
The author thanks this child's mother who graciously agreed to have her son and family participate in this case report.
REFERENCES
1. Schaefer GB. Clinical genetics in pediatric
physical therapy practice? The future. Pediatr Phys Ther. 2001;13:182–184.
2. Sanger WG, Dave B, Stuberg W. Overview of genetics and role of the pediatric physical therapist in the diagnostic process. Pediatr Phys Ther. 2001;13:164–168.
3. Weiss LA, Shen Y, Korn JM, et al. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008;357(7):667–675.
4. Ballif BC, Hornor SA, Jenkins E, et al. Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2. Nat Genet. 2007;39(9):1071–1073.
5. Fernandez BA, Roberts W, Chung B, et al. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet. 2010;47:195–203.
6. Bachmann-Gagescu R, Mefford HC, Cowan C, et al. Recurrent 200-kb deletions of 16p11.2 that include the sh2b1 gene are associated with developmental delay and obesity. Genet Med. 2010;12(10):641–647.
7. Hanson E, Nasir RH, Fong A, et al. Cognitive and behavioral characterization of 16p11.2 deletion syndrome. J Dev Behav Pediatr. 2010;31(8):649–657.
8. Shinawi M, Liu P, Kang S-H, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioral problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010;47:232–241.
9. Rosenfeld JA, Coppinger J, Bejjani BA, et al. Speech delays and behavioral problems are predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications. J Neurodevelop Discord. 2010;2:26–38.
10. Bassuk AG, Geraghty E, Wu S, et al. Deletions of 16p11.2 and 19p13.2 in a family with intellectual disability and generalized epilepsy. Am J Med Genet Part A. 2012;161A:1722–1725.
11. Barge-Schaapveld DQ, Maas SM, Polstra A, Knegt LC, Hennekam RC. The atypical 16p11.2 deletion: a not so atypical microdeletion syndrome? Am J Genet Part A. 2010;155:1066–1072.
12. Hempel M, Brugues NR, Wagenstaller J, et al. Microdeletions syndrome 16p11.2-p12.2: clinical and molecular characterization. Am J Med Genet Part A. 2009;149A:2106–2112.
13. Bochukova EG, Huang N, Keogh J, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463(7281):666–670.
14. Bardakjian TM, Kwok S, Slavotinek AM, Schneider AS. Clinical report of microphthalmia and optic nerve colonoma associated with a de novo microdeletion of chromosome 16p11.2. Am J Med Genet. 2010;152A(12):3120–3.
15. Kino T, Pavlatou MG, Moraitis AG, Nemery RL, Raygada M, Stratakis CA. ZNF764 haploinsufficiency may explain partial glucocorticoid, androgen, and thyroid hormone resistance associated with 16p11.2 microdeletion. J Clin Endocrinol Metab. 2012;97(8):E1557–E1566.
16. Shiow LR, Paris K, Akana MC, Cyster JG, Sorensen RU, Puck JM. Severe combined immunodefiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a coronin-1a mutation and a chromosome 16p11.2 deletion. Clin Immunol. 2009;131(1):24–30.
17. Adams RC, Tapia C. Early intervention, IDEA Part C Services, and the medical home: collaboration for best practice and best outcomes. Pediatrics. 2013;132:e1073–e1088.
18. IDEA Part C Regulations. Federal Register.
http://www.birth23.org/files/AboutB23/FederalRegs.pdf . Accessed September 12, 2013.
19. American
Physical Therapy Association. Guide to Physical Therapist Practice: 2nd Edition Revised. Philadelphia, PA: WB Saunders Co.; 2003.
20. Newborg J. Battelle Developmental Inventory 2nd Edition: Examiner's Manual. Itasca, IL: Riverside Publishing; 2005.
21. International Classification of Functioning, Disability and Health (ICF). Geneva, Switzerland: World Health Organization; 2001.
http://www.who.int/classifications/icf/en/ . Accessed September 12, 2013.
22. Dumont-Mathieu T, Fein D. Screening for autism in young children: the Modified Checklist for Autism in Toddlers (M-CHAT) and other measures. Ment Retard Dev Disabil Res Rev. 2005;11:253–262.
23. Chlebowski C, Robins DL, Barton ML, Fein D. Large-scale use of the Modified Checklist for Autism in low-risk toddlers. Pediatrics. 2013;131(4):e1121–e1127.
24. Brown T, Subel C. Known-group validity of the Infant Toddler Sensory Profile and the Sensory Processing Measure-Preschool. J Occup Ther Schools Early Inter. 2013;6(1):54–72.
25. Folio MR, Fewell RR. Peabody Developmental Motor Scales 2nd Edition: Examiner's Manual. Austin, TX: PRO-ED, Inc; 2000.
26. Connolly BH, McClune NO, Gatlin R. Concurrent validity of the Bayley-III and the Peabody Developmental Motor Scale-2. Pediatr Phys Ther. 2012;24(4):345–352.
27. Parks S, Celeste M. Inside HELP: Administrative and Reference Manual for HELP (The Hawaii Early Learning Profile) Birth-3 Years. Menlo Park, CA: VORT Corporation; 1992.
28. Squires J, Bricker D. An Activity-Based Approach to Developing Young Children's Social Emotional Competence. Baltimore, MD: Paul H. Brookes Publishing; 2007.
29. Dunst CJ, Bruder MB. Valued outcomes of service coordination, early intervention, and natural environments. Except Child. 2002;68:361–375.
30. Rush DD, Sheldon ML, Hanft BE. Coaching families and colleagues: a process for collaboration in natural settings. Infants Young Child. 2003;16:33–47.
31. Dirks T, Hadders-Algra M. The role of the family in intervention of infants at high risk of cerebral palsy: a systematic analysis. Dev Med Child Neurol. 2011;53(suppl 4):62–67.
32. Ulrich BU. Opportunities for early intervention based on theory, basic neuroscience, and clinical science. Phys Ther. 2010;90(12):1868–1880.
33. Levac D, Wishart L, Missiuna C, Wright V. The application of motor learning strategies within functionally based interventions for children with neuromotor conditions. Pediatr Phys Ther. 2009;21:345–355.
34. Monson R, Deitz J, Kartin D. The relationship between awake positioning and motor performance among infants who slept supine. Pediatr Phys Ther. 2003;15:196–203.
35. Shelden ML, Rush DR. A primary coach approach to teaming and supporting families in early childhood education. In: McWilliams RA, ed. Working With Families of Young Children With Special Needs. NY: Guilford Publications; 2010:175–202.
36. Bondy A, Frost L. The picture exchange communication system. Behav Modif. 2001;25(5):725–744.
37. Dong VA, Tung IH, Fong KN. Studies comparing the efficacy of constraint-induced movement therapy and bimanual training in children with unilateral cerebral palsy: a systematic review. Dev Neurorehabil. 2013;16(2):133–143.
38. Myers CT, Effgen SK, Blanchard E, Southall A, Wells S, Miller E. Factors influencing physical therapists' involvement in preschool transitions. Phys Ther. 2011;91:656–664.
39. Boyle JD, Boyle EM. Born just a few weeks early: does it matter? Arch Dis Child Fetal Neonatal Ed. 2013;98:F85–F88.
40. Sutton PS, Darmstadt GL. Preterm birth and neurodevelopment: a review of outcomes and recommendations for early identification and cost-effective interventions. J Trop Pediatr. 2013;59(4):258–265.
