TABLE 1.

Health considerations by age for individuals with Angelman syndrome

Age	Medical eval	Anticipatory guidance	Medical referrals	Labs	Diagnostic	Medication/supplement considerations
Age of diagnosis	Feeding Vision ‐CVI ‐strabismus GERD Growth & Development Tone Seizures	Genetic counseling Hold upright during feeding and for 30 minutes after feeding (GERD precautions) Discuss low‐carbohydrate, higher protein and fat foods towards implementation of LGIT diet Early intervention services Assess sleep Seizures precautions/management Monitor constipation Sufficient environmental stimulation Support groups Clinical research a	Genetics/Genetic Counseling Neurology Ophthalmology GI/Nutrition OT ‐Address sensory needs PT ‐Orthotics ‐Aqua therapy SLP ‐AAC	Genetic confirmation (See Figure 1) If failure to thrive is present: CMP, CBC, thyroid studies, vitamin D, magnesium, phosphorus Assess patient produces ketones as expected if initiating diet: acylcarnitine profile, urine organic acids, free and total carnitine Additional labs before initiating/monitoring diet: selenium, zinc, ionized calcium, BHB, lipid panel, carnitine, urine calcium Ferritin with ESR	Hip x‐ray (especially if not ambulatory) Spine x‐ray EEG, especially if suspect seizures Feeding evaluation ‐VFSS if needed	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet
1–3 years old	Growth & development Vision ‐CVI ‐strabismus Feeding Seizures Sleep Behavior	Early intervention services LGIT/ketogenic diets Routines ‐Bedtime ‐Toileting (see Figure S1) ‐Daily activities ‐Behavioral modification Limit‐setting Seizures Support groups Clinical research a	Neurology Medical Home/AS specialist Ophthalmology Developmental Pediatrician GI/Nutrition Sleep (if not addressed by another specialist) OT ‐Address sensory needs PT ‐Orthotics ‐Aqua therapy ‐hippotherapy SLP ‐AAC Vision therapy Equipment referral (specialized stroller, car seat, Safe sleep bed) Applied behavioral analysis/behavioral therapy Dental care	Ferritin and ESR CBC Vitamin D Diet Monitoring ‐CBC ‐Vitamin D ‐CMP ‐Selenium ‐Magnesium ‐Phosphorus ‐Zinc ‐Carnitine ‐BHB ‐Lipid panel ‐Urine calcium ‐Ionized calcium	Hip x‐ray (especially if not ambulatory) Spine x‐ray Consider EEG Feeding evaluation	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet Sleep Management (see Figure 3) Consider transition to Safe Sleep bed Behavior Management (see Figure 4) Treat constipation with stool softener +mild stimulant (e.g. senna, magnesium)
1–5 years old	Growth & development Seizures Vision ‐CVI ‐strabismus Feeding Scoliosis Sleep Behavior Mobility	Early intervention services/IEP preparation Seizures LGIT/ketogenic diets Routines ‐Bedtime ‐Toileting (see Figure S1) ‐Daily activities ‐Behavioral modification strategy Limit‐setting Constipation (can be linked to sleep disturbance, seizures, behavior changes) Activity ‐Adaptive sports ‐Exercise 30–90 minutes per day Monitor gait over time Sleep ‐Consider role of seizures at night Support groups Clinical research a	Neurology Medical Home/AS specialist Developmental Pediatrician (if not addressed by another specialist) Sleep (if not addressed by another specialist) Ophthalmology GI/Nutrition SLP ‐AAC focus OT PT ‐Orthotics ‐strengthening ‐Aqua therapy ‐Hippotherapy ‐SPIDER therapy Vision therapy Applied behavioral analysis/behavioral therapy Dental care	Ferritin and ESR Vitamin D Diet Monitoring ‐CBC ‐Vitamin D ‐CMP ‐Selenium ‐Magnesium ‐Phosphorus ‐Zinc ‐Carnitine ‐BHB ‐Lipid panel ‐Urine calcium ‐Ionized calcium	Hip x‐ray (especially if not ambulatory) Spine x‐ray Consider EEG Feeding evaluation Consider sleep study (best if in home environment) DEXA scan every 2 years if on low carbohydrate diet	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet Sleep Management (see Figure 3) Consider transition to Safe Sleep bed Behavior Management (see Figure 4) Treat constipation daily with stool softener +mild stimulant (e.g. senna)
5–13 years‐old	Growth & development Seizures Sleep Behavior Vision Scoliosis Mobility Weight management	Seizures Non‐epileptic myoclonus may emerge around the time of puberty Sleep LGIT/ketogenic diets Hyperphagia Constipation Mobility (change in gait pattern, consider pain) Constipation (can be linked to sleep disturbance, seizures, behavior changes) Anxiety Puberty ‐Monitor seizures ‐Behavior changes ‐Plan for suppression of menses (in females) Routines/consistency in all environments ‐Bedtime ‐Toileting (see Figure S1) ‐Daily activities ‐Behavioral modification strategy ‐Safety plan (tracking if elopement is a concern) IEP intervention ‐PT b ‐SLP: AAC integration ‐OT: focus on independence, activities of daily living ‐Para pro ‐Inclusion where appropriate ‐Functional behavioral assessment and ABA/behavioral therapy services ‐Seizure plan (prophylactic medications) •Clinical Research a	Neurology Medical Home/AS specialist Ophthalmology GI/Nutrition Sleep (if not addressed by another specialist) Orthopedics (as needed for mobility, scoliosis, DDH) Obstetrics & gynecology SLP ‐AAC focus OT PT ‐Orthotics ‐strengthening ‐Aqua therapy ‐Hippotherapy ‐SPIDER therapy Vision therapy Applied behavioral analysis/behavioral therapy Dental care IEP advocate	Ferritin and ESR Vitamin D CMP CBC Lipid panel Diet Monitoring ‐CBC ‐Vitamin D ‐CMP ‐Selenium ‐Magnesium ‐Phosphorus ‐Zinc ‐Carnitine ‐BHB ‐Lipid panel ‐Urine calcium ‐Ionized calcium	Hip x‐ray (especially if not ambulatory) Spine x‐ray NEM: rule out underlying causes – constipation, worsening sleep, decreased appetite and poor nutrition, changes in mobility related to decreased ROM and pain) DEXA every 2 years if on low carbohydrate diet long‐term, non‐ambulatory, delayed puberty or history of >2 fractures	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet Sleep Management (see Figure 3) Consider transition to Safe Sleep bed Behavior Management (see Figure 4) Treat constipation daily with stool softener +mild stimulant (e.g. senna)
13–21 years‐old	Independence with ADLs Transition Seizures Sleep Behavior Scoliosis Mobility AAC use and integration Weight management	Seizures Non‐epileptic myoclonus may emerge around the time of puberty Sleep LGIT/ketogenic diets Hyperphagia Constipation Mobility (change in gait pattern, consider pain) Constipation (can be linked to sleep disturbance, seizures, behavior changes) Anxiety Puberty ‐Monitor seizures ‐Behavior changes ‐Plan for suppression of menses (in females) Routines/consistency in all environments Bedtime Toileting (see Figure S1) Daily activities Behavioral modification strategy Safety plan (tracking if elopement is a concern) IEP intervention PT b SLP: AAC integration OT: focus on independence, ADL Para pro Inclusion where appropriate Functional behavioral assessment and behavioral therapy services Seizure plan (prophylactic medications) Clinical Trials Socialization Vocational opportunities Guardianship Transition of care Support groups DDA services Clinical Research a	Neurology Medical Home/AS specialist Ophthalmology Sleep (if not addressed by other specialist) GI/Nutrition Orthopedics (as needed for mobility, scoliosis) Obstetrics & gynecology SLP ‐AAC focus OT ‐Focus on function and ADLs PT ‐Orthotics ‐strengthening ‐Aqua therapy ‐Hippotherapy ‐SPIDER therapy Applied behavioral analysis/behavioral therapy Dental care IEP advocate	Ferritin and ESR Vitamin D Diet Monitoring ‐CBC ‐Vitamin D ‐CMP ‐Selenium ‐Magnesium ‐Phosphorus ‐Zinc ‐Carnitine ‐BHB ‐Lipid panel ‐Urine calcium Ionized calcium	Spine x‐ray NEM: rule out underlying causes – constipation, worsening sleep, decreased appetite and poor nutrition, changes in mobility related to decreased ROM and pain) DEXA every 2 years if on low carbohydrate diet long‐term, non‐ambulatory, delayed puberty or history of >2 fractures	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet Sleep Management (see Figure 3) Consider transition to Safe Sleep bed Behavior Management (see Figure 4) Treat constipation daily with stool softener +mild stimulant (e.g. senna)
Adults	Independence with ADLs Seizures Sleep Behavior Scoliosis Mobility AAC use and integration Weight management	Non‐epileptic myoclonus Sleep LGIT/ketogenic diets Hyperphagia Constipation Mobility (change in gait pattern, consider pain) Introduction and/or use of AAC Constipation (can be linked to sleep disturbance, seizures, behavior changes) Anxiety Puberty ‐Monitor seizures ‐Behavior changes ‐Plan for suppression of menses (in females) Routines/consistency in all environments ‐Bedtime ‐Toileting (see Figure S1) ‐Daily activities ‐Behavioral modification strategy ‐Safety plan (tracking if elopement is a concern) Seizures Socialization Vocational training Guardianship Transition of care Support groups DDA Preventive Medicine for adults ‐Breast examination/ mammograms ‐Prostate examination ‐Colonoscopy Clinical research a	Medical Home/AS specialist Neurology Ophthalmology Sleep (if not addressed by other specialist) GI/Nutrition Orthopedics (as needed for mobility, scoliosis) Obstetrics & gynecology SLP ‐AAC focus OT ‐Focus on function and ADLs PT ‐Orthotics ‐strengthening ‐Aqua therapy ‐Hippotherapy ‐SPIDER therapy Applied behavioral analysis/behavioral therapy Dental care	Ferritin and ESR Vitamin D Diet Monitoring ‐CBC ‐Vitamin D ‐CMP ‐Selenium ‐Magnesium ‐Phosphorus ‐Zinc ‐Carnitine ‐BHB ‐Lipid panel ‐Urine calcium ‐Ionized calcium	Spine x‐ray Consider EEG Consider sleep study (best if in home environment) NEM: rule out underlying causes – constipation, worsening sleep, decreased appetite and poor nutrition, changes in mobility related to decreased ROM and pain) DEXA every 2 years if on low carbohydrate diet long‐term, non‐ambulatory, delayed puberty or history of >2 fractures DEXA scan for females >65 years old to screen for osteoporosis	Diet: LGIT or ketogenic diet Seizure management (see Figure 2) MCT oil to support diet/constipation Levocarnitine if level borderline or low in patient on low carbohydrate diet Sleep Management (see Figure 3) Consider transition to Safe Sleep bed Behavior Management (see Figure 4) Treat constipation daily with stool softener +mild stimulant (e.g. senna) Preventive healthcare as guidelines recommend for adults (e.g. Pap smear, prostate screening, breast exam, mammogram, colonoscopy); however, anesthesia is required

Abbreviations: AAC, augmentative and assistive communication device; ABA, applied behavioral analysis; ADL, activity of daily living; AS, Angelman Syndrome; BHB, beta‐hydroxybutyrate; CBC, complete blood counts; CMP, comprehensive metabolic panel; CVI, cortical visual impairment; DDA, Developmental Disabilities Administration; DEXA, dual‐energy x‐ray absorptiometry; ESR, erythrocyte sedimentation rate; GERD, gastroesophageal reflux disease; GI, gastroenterology; IEP, individualized education plan; LGIT, low glycemic index therapy; MCT, medium chain triglycerides; NEM, non‐epileptic myoclonus; OT, occupational therapy; PT, physical therapy; SLP, speech & language pathology; SPIDER, Strengthening Program of Intensive Developmental Exercises and Activities for Reaching Maximal Potential; VFSS, video fluoroscopic swallow study.

^a Clinical research opportunities include participation in the Global Angelman Registry, Natural History Study, and currently recruiting clinical trials.

^b PT involvement providing support as needed in collaboration with IEP team to maximize participation within classroom and access of school environment.