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Genetics and Heart Syndromes

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Genetics and Heart Syndromes

  1. 1. Pediatric Genetics Cases Leah W. Burke, MD May 10, 2021
  2. 2. Goals • Use cases to inform the decision making needed for a genetics referral • Understand the components of a genetic evaluation • Become familiar with three syndromes in which the presenting symptom can be a heart murmur
  3. 3. Congenital Heart Defects and Syndromes
  4. 4. Case 1: Coralie • You are seeing a 7 month old in clinic to address her growth issues and colic issues • You hear a heart murmur that you have not heard before • You also notice that her development is slower than her brother’s • She is sent for a genetic and cardiac evaluation
  5. 5. REMEMBER THE RULE OF “TWO/TOO” (when asking questions) • TOO tall • TOO short • TOO early • TOO many • TOO young • TOO different • TWO tumors • TWO generations • TWO in the family • TWO birth defects
  6. 6. Williams Syndrome • Heart defect –Supravalvular aortic stenosis –Stenosis of other arteries –Thought to be due to a defect in the elastin gene
  7. 7. Williams Syndrome • Facial features – Periorbital puffiness – Wide mouth & thick lips – Stellate irides
  8. 8. Williams Syndrome • Neurosensory –Hyperacusis –Musical abilities –Intellectual disability –Relative sparing of language –Cocktail party personality
  9. 9. www.gemssforschools.org
  10. 10. Williams Syndrome • Heart defect – Supravalvular aortic stenosis – Stenosis of other arteries • Facial features – Periorbital puffiness – Wide mouth & thick lips – Stellate irides • Neurosensory – Hyperacusis – Musical abilities – Intellectual disability – Relative sparing of language – Cocktail party personality • Short stature • Kidney abnormalities • Hoarse voice • Hypercalcemia • Continuous gene deletion of 7q11.2, including the elastin gene (ELN)
  11. 11. Case 2: Olivia • You are seeing a newborn for the first time in the nursery • You hear a heart murmur • You have her evaluated by the cardiologist
  12. 12. Noonan Syndrome • Cardiac defects – Pulmonary valve stenosis – Dysplastic (abnormal) pulmonary valve – Hypertrophic cardiomyopathy may be present in early infancy or even develop prenatally
  13. 13. Noonan syndrome Facial features • Eyes –Ptosis –Downslanting palpebral fissures • Ears –Low-set –Posteriorly rotated
  14. 14. Facial landmarks
  15. 15. Innercanthal/Innerpupillary Measurement Hypotelorism Normal Hypertelorism
  16. 16. Innercanthal/Innerpupillary Measurement Hypotelorism Normal Hypertelorism
  17. 17. Ear
  18. 18. Noonan syndrome • Congenital heart defect • Characteristic facies – ptosis, downslanting palpebral fissures, low-set and rotated ears • Short stature • Broad or webbed neck • Unusual chest shape with superior pectus carinatum, inferior pectus excavatum • Apparently low-set nipples • Developmental delay of variable degree • Cryptorchidism • Coagulation defects
  19. 19. Genetics in Noonan Syndrome
  20. 20. Case 3: Kirsten • You are seeing a 3 year old in your office for her well child check-up • You hear a heart murmur on examination • She has some speech delays and has very nasal sounding speech
  21. 21. 22q Deletion Syndrome • Other names – Velocardiofacial syndrome – DiGeorge Syndrome – Shprintzen Syndrome – CATCH 22 – not used by most physicians because of the negative reaction by families • Estimated prevalence is 1 in 2000 to 1 in 4000
  22. 22. 22q Deletion Syndrome • Congenital heart defects are found in 74% • Major cause of mortality (>90% of all deaths) • Conotruncal (area of the outflow tracts) cardiac defects are the most common – Some like interrupted aortic arch are rarely seen other than in 22q deletion – 20% of individuals with Tetraology of Fallot (TOF) have 22q deletion
  23. 23. Craniofacial Features • Short palpebral fissures • Wide nasal bridge with narrow alae nasae • Small mouth • Cleft palate or cleft lip and palate or dysfunctional palate • Structurally and/or functionally asymmetric face • Asymmetric crying facies
  24. 24. Facial landmarks
  25. 25. 22q Deletion syndrome • Cardiac defects • Endocrine – Thymic hypoplasia leading to T-cell abnormalities – Parathyroid hypoplasia • Neurologic/psychologic – Learning problems – ADHD – Autism spectrum disorder – Psychiatric illness as adolescents/adults • Speech – Cleft palate – Velopharyngeal insufficiency (VPI) – Hypernasal Speech problems • Characteristic facial features
  26. 26. Early Cognitive and Behavioral Phenotype • Delayed early motor development • Delayed language • Autism/autism spectrum disorders – 20% • Decreased cognitive scores in toddlers
  27. 27. General Cognitive Ability • In general individuals with 22q Deletion have IQ scores that are lower than their unaffected siblings or other family members • 66% have a non-verbal learning disability (Verbal IQ > performance IQ) – VerbaI IQ averages 75-80 – Performance (non-verbal) IQ averages 70-75 • IQ appears to be lower in familial cases than in de novo cases • Some evidence that IQ scores are lower in boys than in girls
  28. 28. Attention Deficit Disorders • The most frequent behavioral observation • 30-50% meet criteria for ADHD • Reductions in volumes of the frontal lobe and dorsolateral prefrontal cortex in 22q deletion may explain part of the prevalence • Medications such as methylphenidate have been proven useful
  29. 29. Psychiatric Issues • 20% will have a psychiatric diagnosis • Schizophrenia and bipolar disease are the most common • Anxiety disorders are very common
  30. 30. Motor Abilities • Hypotonia in infancy is common and may be significant • Impact on both fine and gross motor • In school may present with difficulties in writing, using scissors, etc • Fine motor skills may be impacted by both the hypotonia and the visual-spatial difficulties
  31. 31. Genes in 22q Deletion • TBX-1 was the first gene to be implicated • Other genes have followed
  32. 32. 22q Deletion Syndrome and Newborn Screening

Editor's Notes

  • One quick way of remembering what are the right questions to ask is “The Rule of Two/Too.”
    Take note of any family member who is…. And who has …..

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