Medical management and surveillance in
22q11.2DS
Kathy Angkustsiri, M.D., M.A.S. Developmental Behavioral Pediatrics Medical Director, 22q Healthy Minds Clinic UC Davis MIND InsEtute Center for Excellence in Developmental DisabiliEes Outline •  What is chromosome 22q11.2 deleEon syndrome (22q11.2DS)? •  Clinical features –  Medical issues and surveillance –  Behavioral and educaEonal concerns •  Summary and recommendaEons All the names…. •
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Velo-­‐cardio-­‐facial syndrome (VCSF) Conotruncal anomaly face syndrome (CAFS) DiGeorge syndrome (DGS) Autosomal dominant Opitz G/BBB syndrome Cayler Cardiofacial syndrome 22q11.2DS 22q11.2 deleEon 22q11.2 deleEon •  EsEmated incidence 1:2000-­‐4000 live births •  Most are “de novo” (new) deleEon –  Affected individuals have a 50% chance of passing the deleEon to offspring (autosomal dominant) •  Large spectrum of involvement –  Heart –  Face/Palate –  Immune –  Developmental –  Others hap://pharyngula.org/index/weblog/comments/
deep_homologies_in_the_pharyngeal_arches/ hap://www.ucdmc.ucdavis.edu/mindinsEtute/research/cabil/cabil_video.html Heart / Cardiac Problems (75%) •
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Tetralogy of Fallot Ventricular Septal Defect Pulmonary Stenosis Vessel anomalies –  Interrupted aorEc arch –  Vascular ring –  Aberrant caroEd vessels •  Echocardiogram, EKG hap://en.wikipedia.org/wiki/Image:Gray506.svg#file Ear, Nose, Throat hap://homepage.mac.com/changcy/endo.htm •  Cleh Palate or Velopharyngeal Incompetence (VPI) (75%) –  Feeding difficulEes –  Nasal regurgitaEon –  Cleh Palate (full, submucous) –  Hypernasal Speech, ArEculaEon disorders •  Chronic ear infecEons, may need PE tubes –  SNHL (10%), CHL (45%) •  Vocal cord paralysis •  Laryngeal web •  Nasendoscopy •  RouEne hearing screens •  Neck MRI if surgical procedures Bifid uvula www.minor9th.com Immunologic Problems (25-­‐30%) •  Low T cells (usually mild with normal funcEon) due to thymus involvement •  AnEbody producEon usually intact •  Usually improves with age •  Recurrent infecEons: ear infecEons, sinusiEs, bronchiEs, pneumonia hap://www.myasthenia.org.au/html/treatments.htm •  Flow cytometry (T and B cell counts), anEbody levels, other immune funcEon tests •  Important to know immune status before giving live vaccines or blood transfusions •  May want to check for adequate vaccine response Endocrine •  Hypoparathyroidism (25%) •  Low calcium levels (hypocalcemia) –  Seizures •  Hypothyroid •  Short stature •  Ionized calcium levels, thyroid levels •  Endocrinology referral if abnormal labs or <3rd percenEle on growth curves GastrointesEnal •
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Feeding/Failure to Thrive ConsEpaEon GERD (gastroesophageal reflux disease) Hernia MalrotaEon Musculoskeletal •
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Cervical spine anomalies Flat feet Chronic leg pain (hypotonia and flat feet) Hypotonia Polydactyly Craniosynostosis •  5 view c-­‐spine x-­‐rays aher age 4 Eye •
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Strabismus (lazy eye) Ptosis ReEnal vessels Hooded eyelids •  Yearly eye exams, including dilaEon Other Systems •  Autoimmune disorders (10%) –
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Blood: platelets (ITP, vWD, Bernard-­‐Soulier), white blood cells Juvenile Rheumatoid ArthriEs (JRA) IgA deficiency Raynaud’s phenomenon Celiac disease ? cancer •  Kidney abnormaliEes (33%) –  Small kidneys –  Duplicated kidneys or renal system •  Renal ultrasound Developmental-­‐Behavioral Concerns •  Developmental Delays –  Motor delays –  Speech and language delays –  Learning disabiliEes •  FSIQ low-­‐average to borderline range •  SomeEmes misleading b/c usually verbal IQ beaer than performance IQ •  DifficulEes with planning, math, and visuospaEal tasks –  Social immaturity Developmental-­‐Behavioral Concerns •  AaenEon Deficit/HyperacEvity Disorder (ADHD) 30-­‐50% –  Impulsivity –  InaaenEve, easily distracted •  Anxiety Disorders: 40-­‐60% –  Specific phobias –  Obsessive Compulsive Disorder –  General Anxiety –  SeparaEon Anxiety Disorder •  Mood disorders Treatments/RecommendaEons •  Varies based on individual needs •  Behavioral •  EducaEonal •  Medical –  Labs/procedures •  Thyroid, calcium, complete blood count, etc. –  MedicaEons ADHD treatment •
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Behavioral intervenEon Classroom modificaEons Parent training MedicaEons –  SEmulants –  Alpha agonists (use with cauEon if cardiac hx) –  AtomoxeEne (Straaera) –  Others SEmulants for ADHD •  Why the concern? –  Cardiac side-­‐effects –  Growth –  PsychoEc symptoms? –  Altered dopamine levels in 22q11.2DS due to COMT? SEmulants in 22q11.2DS •  Gothelf 2004 (4 weeks) –  12 children with ADHD –  Low dose methylphenidate (0.3 mg/kg) •  Gothelf 2011 (6 months) – 0.5 mg/kg –  22 children treated –  No psychoEc/manic symptoms –  Mild elevaEons in blood pressure •  Conclusion: –  methylphenidate is effecEve and usually well-­‐tolerated –  be aware of side effects and potenEal risks –  must weigh risks/benefits with your provider Anxiety treatment •  CogniEve behavioral therapy •  Social skills group •  MedicaEons –  SSRI •  Side effects –  Sleep, headaches, appeEte –  Suicidal thinking Resources •  Early intervenEon –  Speech therapy –  OccupaEonal therapy –  Physical therapy –  Social skills •  School –  IEP classificaEons •  Other Health Impaired (OHI) •  Specific Learning Disability (SLD) •  Speech/Language impairment (SLI) –  504 plan •  Computer assisted learning •  Classroom accommodaEons RecommendaEons •  At diagnosis or at least once –
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Echocardiogram Immune funcEon ENT-­‐nasendoscopy Cervical spine films Renal ultrasound GeneEc counseling •  Yearly –
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Eye exam Hearing exam CBC, calcium, thyroid Dental •  As needed –  Craniofacial/cleh palate team –  Chest MRI to assess vasculature if surgical procedure in neck area –  Endocrinology –  Immunology –  Hematology –  Rheumatology –  Orthopedics –  Gastroenterology –  Neurology –  Developmental pediatrician or child psychiatry –  School involvement Websites •  MIND InsEtute CogniEve Analysis and Brain Imaging Laboratory (CABIL) hap://cabil.mindinsEtute.org •  InternaEonal 22q11.2 FoundaEon hap://www.22q.org/ •  VCSF EducaEonal FoundaEon, Inc. hap://www.vcfsef.org/ •  CHOP The 22q and You Center hap://www.chop.edu/consumer/jsp/division/generic.jsp?
id=74654 •  Chromosome 22 Central www.c22c.org •  Books: •  EducaEng Children with Velo-­‐Cardio-­‐Facial Syndrome by Donna Cutler-­‐Landsman •  Missing GeneEc Pieces. Strategies for Living With VCSF by Sherry Baker-­‐Gomez References •  Bassea, AS, et al. "PracEcal guidelines for managing paEents with 22q11. 2 deleEon syndrome." J Pediatrics 2011; 159.2:332. •  Kobrynski LJ and Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deleEon syndromes. Lancet 2007; 370:1443-­‐52. •  McDonald-­‐McGinn, Emmanuael BS, Zackai EH. 22q11.2 DeleEon Syndrome. GeneReviews; 2005. www.genetests.org •  Shprintzen RJ. 2004 .Velocardiofacial syndrome. In Cassidy SB and Allanson JE, Management of GeneEc Syndromes, p 615-­‐631. New York: Wiley-­‐Liss, Inc. •  Tarquinio, DC, et al. "Growth charts for 22q11 deleEon syndrome.“AJMG part A 2012; 158.11: 2672-­‐2681. Thank you! –  To all of the families who have parEcipated in research –  CogniEve Analysis and Brain Imaging Laboratory (CABIL) Funded by: •  NaEonal InsEtutes of Health –  2R01HD42974, 1R01HD46159, 1RL1NS62412 (Simon) •  Center for Excellence in Developmental DisabiliEes (CEDD) –  AdministraEon on Developmental DisabiliEes 90DD0596 (Hansen) •  UC Davis –  M.I.N.D. InsEtute –  Clinical and TranslaEonal Science Center UL1 RR024146