1. MICHAEL Mcnamara, DO Kristen de Berg, ms, cgc
Mother to Baby: Hereditary causes for congenital heart defects in the newborn
MICHAEL Mcnamara, DO
Kristen de Berg, ms, cgc

2. OBjectives Review early heart development
Overview of congenital heart disease (CHD)
Genetic causes for congenital heart disease
Case presentations

3. Fetal Heart First major organ system to function
Nutritional and oxygen requirements not being met by diffusion alone
More than 500 genes involved with developing the fetal heart
Progenitor cells for the heart come from several sources
Heart first begins to beat at day 22-23
Blood flow at four weeks and heart beat visualized by ultrasound

7. Congenital heart defects
How did this happen?
Why did this happen?
Is it familial/genetic?
Will other family members need screening?
Can it happen again?

8. Risk Factors Influencing heart development
Fetal
Maternal
Familial
Most cases without risk factor

9. Risk Factors - Fetal Abnormal visceral / cardiac situs
Abnormal 4 chamber view, outflow tracts, three vessel
Arrhythmia
Aneuploidy
Two vessel umbilical cord, other fetal malformation
IUGR / polyhydramnios
Hydrops
Twins
Increased nuchal translucency

10. Fetal abnormalities Central Nervous System Thoracic Skeletal
Gastrointestinal
Urogenital

11. Risk factors - maternal
Systemic lupus, Sjogrens syndrome
Diabetes
Phenylketonuria
Viral syndromes
Maternal congenital heart disease
Teratogen exposure
In vitro fertilization

12. Teratogens Anticonvulsants Warfarin Aspirin / NSAIDs
Valproic acid, carbamazepine, phenytoin, phenobarbital
Warfarin
Aspirin / NSAIDs
Tricyclic antidepressants
Lithium
Alcohol
Recreational drugs (cocaine)
Isoretinoin

13. Risk factors - familial
First degree relative with CHD
DiGeorge syndrome
Long QT syndrome
Noonan syndrome
Marfan syndrome
Tuberous sclerosis
Williams syndrome
Tetrology of Fallot repair

14. CHD overview
Congenital heart disease: Structural malformation of the heart present at birth
0.5-1% of all births
25-40% of cases are syndromic
~2% have a first degree relative with CHD
Oyen et al. 2009

15. Septal
LVOT
Conotruncal
Other

17. Condition
Cardiac finding
% with CHD
Trisomy 21
ASD, VSD, AVSD, TOF
40-50%
Trisomy 18
ASD, VSD, PAD, TOF, DORV, CoA, BAV
90-100%
Trisomy 13
ASD, VSD, PDA, HLHS
80%
Monosomy X
CoA, BAV, AS, HLHS
25-35%
22q11.2 deletion
Aortic arch, TOF, truncus
75%
Williams
Supravalvar AS, PPS
50-85%
Holt-Oram
ASD, VSD, AVSD, AV conduction
Noonan
PS, AVSD, HCM, CoA
50-80%
CHARGE
conotruncal defects, VSD, ASD
74%
Kabuki
CoA, other left-sided obstruction, VSD
90%:
Sotos
ASD, VSD
25%

19. Case #1
31 year old G2P0 at 12+3 weeks gestation referred for enlarged nuchal translucency vs cystic hygroma seen on 1st trimester U/S.
Both parents are known carriers for cystic fibrosis

20. Case #1
31 year old G2P0 at 12+3 weeks gestation referred for enlarged nuchal translucency vs cystic hygroma seen on 1st trimester U/S.
Turner syndrome?
Cardiac defect?
Trisomy 21?
Patient offered diagnostic testing or NIPS (non invasive prenatal screening) for chromosome abnormalities (trisomies 13, 18, 21 and XY).
Elected to proceed with NIPS.

22. Case #1 Patient presents at 19+5 days for detailed anatomy scan
Suspected fetal heart defect: VSD vs AV canal, possible coarctation of aorta.
Dilated fetal kidneys

23. Case #1
Upon closer examination, the mother had some subtle physical traits suspicious of an underlying genetic condition.

24. Noonan syndrome

25. Case #1
The mother had been evaluated as a child by genetics for these “phenotypic” changes
At that time, her genetic testing was normal for Noonan syndrome.
Fast forward 20+ years, we discussed discussed changes in testing
She RE-tested for Noonans syndrome

26. Case #1 results

27. Noonan syndrome

28. Case #1 Amniocentesis for diagnosis
Autosomal dominant for Noonan’s (50% chance)
Cystic fibrosis (25% chance, 50% chance for carrier)
Results
SOS1 - postitive
Cystic fibrosis - negative

29. Case #1 management
Now that we know why there’s a fetal heart defect, how do we take care of baby AND mom?
Prenatal/postnatal care:
Edema?
Cardiac consults? (mom and baby?)
Peds Cardiology consult
Maternal echocardiogram negative previously

30. Management for noonan syndrome
Multi-system evaluations
Cardiac evaluations (echo & EKG)
Ophthalmologic evaluation
Hearing evaluation
Renal ultrasound
Clinical and x-rays assessment of spine and rib cage
Brain and spine MRI if neuro symptoms present
Developmental evaluation
Consult with genetics

31. Case #1 management Spontaneous labor at term
Vaginal delivery with forceps
Baby to the NICU
Transferred to University of Michigan Ann Arbor for repair
Maternal condition diagnosed with fetal findings!

32. Case #2 23-year-old gravida 3, para 1 at 20 weeks +1 day
Maternal history of Holt-Oram syndrome with a previously affected child

33. Holt Oram syndrome aka “heart-hand syndrome” Autosomal dominant
Abnormalities associated with:
Bone of the hand and arm
Cardiac defects
TBX5 pathogenic variants

34. Management for Holt-oram
System/Concern
Evaluation
Comment
Musculoskeletal
Physical exam for limb involvement
Hand & upper-limb radiographs
Cardiac
Chest radiograph
Identify enlarged pulmonary arteries caused by pulmonary HTN or cardiomegaly
Echo
Identify septal defects or other CHD
EKG
Identify cardiac conduction disease
Other
Consult w/ genetics regarding recurrence
Refer family members for examination

35. Case #2 Management Ultrasound findings at 20 weeks Triphalangeal thumb
Congenital heart defect, AV canal defect
Peds Cardiology consult
Delivery at tertiary care center
Maternal condition helped with fetal diagnosis and management!

36. Case #3
27yr-old female presents at 20w6d due to previous IUFD and family history of heart defects
Previous 16 week loss of unknown etiology, normal aCGH.
Spouse with heart surgery as baby
Family history of trisomy 21 (patient’s sibling)

38. Case #3
Double-outlet right ventricle with d-transposition of the great arteries and large muscular ventricular septal defect
Patient’s partner: d-transposition of great arteries, ventricular septal defect, atrial septal defect, and straddling mitral valve

39. Case #3
Patient elected to proceed with amniocentesis

40. Case #3 Peds Cardiology consult Term delivery
Transferred to University of Michigan Ann Arbor for repair

41. So why does CHD occur more in some families?+
Genetic variants
Epigenetic factors
Environmental factors
Hemodynamic factors

42. Counseling for Congenital heart defects
How did this happen?
Why did this happen?
Is it familial/genetic?
Will other family members need screening?
Can it happen again?

43. Conclusion - CHD
Most common birth defect 3-4/1000 needing surgical repair in first year of life
Many different risk factors though most without a risk factor
Diagnosis and post delivery counseling
Genetic counseling for recurrence in future pregnancies and possibly with other family members

44. This Presentation has the ultrasound images removed
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