Factors influencing pulmonary arterial pressure in three related patients with Cantú syndrome: glyburide may provide precision care

Abstract

A range of pulmonary arterial pressures was observed in three related patients with Cantú syndrome. The incident patient developed a moderately high pulmonary vascular resistance. Several factors influenced the severity of his pulmonary vascular disease and the events, which ultimately resulted in his death. However, he had an acute improvement in blood pressure and respiratory support after a single dose of glyburide when he was critically ill. The father and sister of the incident patient have evidence of mildly increased pulmonary arterial pressure with normal pulmonary vascular resistance. They are being treated with glyburide to potentially decrease the high cardiac output associated with a gain in K_ATP channel function. Additional experience with glyburide or other K_ATP channel inhibitors is needed to determine the most appropriate agent, dose, time, and duration of treatment for patients with Cantú syndrome.

Keywords

Adenosine triphosphate-sensitive potassium channel / Cantú syndrome / glyburide / high cardiac output / pulmonary hypertension

References

[1] Cantú JM,Sánchez-Corona J,Nazará Z.A distinct osteochondrodysplasia with hypertrichosis- Individualization of a probable autosomal recessive entity.Hum Genet1982;60:36-41

[2] van Bon BW,Grange DK.Cantú syndrome is caused by mutations in ABCC9.Am J Hum Genet2012;90:1094-101 PMCID:PMC3370286

[3] Harakalova M,Terhal PA.Dominant missense mutations in ABCC9 cause Cantú syndrome.Nat Genet2012;44:793-6

[4] Grange DK,McClenaghan C.Cantú syndrome: findings from 74 patients in the international Cantú syndrome registry.Am J Med Genet C Semin Med Genet2019;181:658-81 PMCID:PMC7654223

[5] Huang Y,Harter TM.Cardiovascular consequences of KATP overactivity in Cantu syndrome.JCI Insight2018;3:121153 PMCID:PMC6129117

[6] Singh GK,Aggarwal M.A unique high-output cardiac hypertrophy phenotype arising from low systemic vascular resistance in Cantu syndrome.J Am Heart Assoc2022;11:e027363 PMCID:PMC9798820

[7] McClenaghan C,Matkovich SJ.The mechanism of high-output cardiac hypertrophy arising from potassium channel gain-of-function in Cantú syndrome.Function2020;1:zqaa004 PMCID:PMC7446247

[8] Parrott A,Brown N,Riley L.Cantu syndrome: a longitudinal review of vascular findings in three individuals.Am J Med Genet A2020;182:1243-8

[9] McClenaghan C,Nichols CG.Pulmonary hypertension and ATP-sensitive potassium channels.Hypertension2019;74:14-22 PMCID:PMC6561811

[10] Ma A,Kirk EP.Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain-of-function variant: initial experience.Am J Med Genet A2019;179:1585-90 PMCID:PMC6899598

[11] Timlin MR,Delaney HM,Percival CS.Development of pulmonary hypertension during treatment with diazoxide: a case series and literature review.Pediatr Cardiol2017;38:1247-50

[12] Wang SW,Rowlands DJ.Diazoxide in treatment of primary pulmonary hypertension.Br Heart J1978;40:572-4 PMCID:PMC483448

[13] Hall DR.Reversibility of primary pulmonary hypertension during six years of treatment with oral diazoxide.Br Heart J1987;58:420 PMCID:PMC1277279

[14] Chan NS,Kenmure AC.Reversibility of primary pulmonary hypertension during six years of treatment with oral diazoxide.Br Heart J1987;57:207-9. PMCID:PMC1277110

[15] Patel N.New-onset neonatal pulmonary hypertension associated with a rhinovirus infection.Can Respir J2012;19:33-4 PMCID:PMC3299049

[16] Pedraza-Bernal AM,Acuña-Cordero R.Predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.J Med Virol2016;88:754-9

[17] Houtman MJC,Qile M.Glibenclamide and HMR1098 normalize Cantú syndrome-associated gain-of-function currents.J Cell Mol Med2019;23:4962-9. PMCID:PMC7346732

[18] McClenaghan C,Yan Z.Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity.J Clin Invest2020;130:1116-21 PMCID:PMC7269588

[19] Kerstein D,Hsu DT,Gersony WM.Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension.Circulation1995;91:2028-35

[20] Sandoval J,Pulido T.Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension: a therapeutic alternative for patients nonresponsive to vasodilator treatment.J Am Coll Cardiol1998;32:297-304.

[21] Allen BW,Piantadosi CA.Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation.Trends Mol Med2009;15:452-60 PMCID:PMC2785508

[22] Pinto E Vairo F,Vitek CRR.Implementation of genomic medicine for rare disease in a tertiary healthcare system: mayo clinic program for rare and undiagnosed diseases (PRaUD).J Transl Med2023;21:410

[23] Davis MJ,Nichols CG.K_ATP channels in lymphatic function.Am J Physiol Cell Physiol2022;323:C1018-35 PMCID:PMC9550566

[24] Demirel F,Çetin II,Arasli A.Pulmonary hypertension and reopening of the ductus arteriosus in an infant treated with diazoxide.J Pediatr Endocrinol Metab2011;24:603-5.