4/18/2018 HPI- February 2012 Genetic Testing in Pediatric 22 - - PDF document

4/18/2018

Genetic Testing in Pediatric Pulmonary Hypertension: A Case Review

Anna Brown, DNP CPNP Division of Pulmonary Medicine Monroe Carell Jr. Children’s Hospital at Vanderbilt April 19, 2018

HPI- February 2012

• 22 month old white male
• Episodes that resemble seizures lasting about 5-20 minutes
• Pale
• Unresponsive
• Blue discoloration around mouth
• Apnea
• Loss of muscle tone
• Seen by local cardiologist

– Normal ECHO and EKG

• Seen by neurology

– EEG and MRI- negative – Started on Lamictal for suspected seizure disorder

History

• Full term
• Uneventful antenatal course
• There was no h/o any neonatal seizures, hyperbilirubinemia,

intraventricular hemorrhage or ventilation requirements.

• Family History was positive for

– Father’s side with multiple cases of epilepsy – Father also had two siblings die at ages 4 and 5 of unknown cardiopulmonary causes

Social History

• Lives with mother and father in rural TN east of Chattanooga
• He is the only biological child of mother and father, but jointly

there are 7 other kids in the house ranging from ages 2-19

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HPI- May 2013 (note- 15 months later)

• Continued episodes, becoming more frequent
• Followed by Erlanger Children’s Hospital Cardiology every 6-12

months – Repeat ECHO showed RVH, normal structure, normal function – CBC normal – Chest CT showed enlarged main PA and vascular congestion

Right Heart Catheterization (RHC)

• June 7, 2013 Erlanger Children’s Hospital performed a RHC due to

concern for pulmonary hypertension in the setting of syncope and cardiomegaly

• Diagnoses confirmed on RHC and he was referred to Vanderbilt

Children’s Hospital Pediatric Pulmonary Group for management of PH

Systemic Pressure PA Pressure Baseline 73/37 (51) 73/34 (53) 100% FiO2 75/38 (52) 68/29 (48) 100% FiO2 + 40 ppm NO 82/41 (58) 73/31 (62)

Consult with Pediatric Pulmonary Hypertension Team at VCH

• June 14, 2013
• Reviewed clinical course and RHC
• Repeated ECHO
• Ordered sleep study- normal
• Started on ERA therapy- Ambrisentan
• Added MVI with iron
• Discussed activity restriction

Consult with Pediatric Pulmonary Hypertension Team at VCH

• Confirmed the diagnosis of Pulmonary Hypertension, likely iPAH, but

needed further investigation.

• Due to location of family, concerned he might be heritable PH

Nashville Grundy County- home of “Family 14” Largest known family with HPAH

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Vanderbilt and Familial PAH

(Loyd, Primm, & Newman, 1984) Gender disparity 2-3 Females : 1 male

(Updated Dec 2011 (Pulm Circ)—initial pub by Loyd, Primm, Newman , 1984)

Reduced Penetrance: 27% carriers get PAH Females: 42% Males: 14%

Larkin AJRCCM 2012

The Initial Loyd/Newman Family: 39 Confirmed PAH

Nashville Grundy County Hometown of DW

BMPR2 mutations in PAH

Type of PAH Reported mutation prevalence

Familial PAH > 75% Idiopathic PAH 20% Congenital heart disease 6% Scleroderma Not detected HIV Not detected Hemolytic disease Not reported

• Population prevalence: unknown but very rare

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Ordering Genetic Testing in PH

• www.concertgenetics.com

References

Ivy, D. D., Abman, S. H., Barst, R. J., Berger, R. M., Bonnet, D., Fleming, T. R… & Beghetti, M. (2013). Pediatric pulmonary

• hypertension. Journal of the American College of Cardiology,

62(25). doi: doi:10.1016/j.jacc.2013.10.028 Loyd, Primm, & Newman. (1984). Am Rev Respir Disease, 129(1):194-7. Humbert, M., Sitbon, O., & Simonneau, G. (2004). Treatment of pulmonary arterial hypertension. New England Journal of Medicine, 351. doi: 10.1056/NEJMra040291 Zaiman, A., Fijalkowska, I., Hassoun, P. M., & Tuder, R. M. (2005). One hundred years of research in the pathogenesis of pulmonary

• hypertension. American Journal of Respiratory Cell Molecular

Biology, 33(5). 425-31.