The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension

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The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension.

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Haarman MG, Kerstjens-Frederikse WS, Vissia-Kazemier TR, Breeman KTN, Timens W, Vos YJ, Roofthooft MTR, Hillege HL, Berger RMF.
J Pediatr. 2020 Jun 2:S0022-3476(20)30689-2. doi: 10.1016/j.jpeds.2020.05.051. Online ahead of print.
PMID: 32502478

Take Home Points:

  • Prevalence of pulmonary arterial hypertension (PAH)-associated gene disorders and other genetic disorder was high in pediatric patients with PAH.
  • In this study, 27% had a PAH-associated gene mutation/variant, 17% had a genetic disorder with an established association with PAH and in 23% genetic disorders without an established association with PAH were identified.
  • Underlying genetic mutation impact survival and can be useful in risk stratification.

Dr Shaji Menon

Comment from Dr. Shaji Menon (Salt Lake City, Utah), section editor of Pediatric Cardiology Journal Watch:   This study describes the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry. The study also explores genotype-phenotype associations and outcomes. Of the 70 subjects in the study 19 (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beal’s syndrome, and various copy number variations). Of the 70 children tested, 40 children were diagnosed with isolated PAH. Transplant-free survival, unadjusted for clinical variables, varied significantly between groups of children with different genetic disorders. Children with CbIC deficiency and children with PVOD had the worst unadjusted outcome with a median transplant-free survival of <1 year, whereas pediatric TBX4 variant carriers showed the most favorable outcome.

distribution of PAH

genetic architecture

trasplant free survival of children with PAH

Atarim

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