RARE CAUSE OF PULMONARY HYPERTENSION

Rare cause of Pulmonary Hypertension

Priyanka B^1,*, Arjun G², S. Aravindakumar³

¹Duty Medical officer, Department of Cardiology, Kauvery Heart City, Trichy, India

²MEM Postgraduate, Kauvery Hospital, Trichy, India

³Chief Consultant Interventional Cardiologist, Kauvery Heart City, Trichy, India

Abstract

Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease. Very few patients suffering from HHT present with associated pulmonary arterial hypertension (PAH), which may result in a poor prognosis. ACVRL1 mutations have been recognized to lead to a combination of HHT and PAH for several years. In this article, we explore a case with a rare occurrence of HHT with PAH. For a 11-year-old boy, clinical manifestations and treatment as well as genetic analysis of family members are reviewed, to raise awareness of this multimorbidity.

Case Presentation

An 11-year-old boy came with a history of syncope 2 months back. He had a family history of sudden cardiac death of his younger sister at the age of 8 years due to severe PAH, and a family history of epistaxis for his father, uncle and his grandparents.

His physical examination revealed no abnormality, and laboratory investigations were within normal limits.

Echocardiography revealed severe PAH with good biventricular function. His CT pulmonary angiogram showed cardiomegaly with a dilated pulmonary artery and no evidence of pulmonary thromboembolism.

Given the above findings, he was diagnosed with possible HHT. To find out any reversible causes of the disease, a Cath study was done which revealed severe PAH, and pulmonary vasoreactivity testing was negative.

Genetic testing confirmed an ACVRL1 mutation. On screening his family, the patient’s grandparents, father, and siblings including newborn were all found to have pulmonary hypertension. He was managed with Tadalafil (PDE5 inhibitor) and ambrisentan (endothelin receptor antagonist).

Pedigree diagram

Discussion

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant inherited disorder.

HHT consist of two main subtypes, HHT type 1 and HHT type 2, which result from mutations in the ENG gene on chromosome 9 encoding the protein endoglin, and from mutations in the activin receptor-like kinase (ACVRL1) gene on chromosome 12, encoding the protein ALK-1 respectively.

The clinical diagnosis is based on the four Curaçao criteria which consist of the following:

(1) Spontaneous, recurrent epistaxis;

(2) Multiple telangiectasia at characteristic sites (lips, oral cavity, fingers, nose);

(3) Visceral lesions (gastrointestinal telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs); and

(4) A first-degree relative with HHT.

Three criteria suffice for a definitive diagnosis of HHT, and two criteria are considered as â€œpossibleâ€ HHT.

Pulmonary hypertension is a haemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure (mPAP) equal to or more than 25 mmHg as assessed by right heart catheterisation. Pulmonary Hypertension is a progressive disease of many origins, affecting more than 100 million people worldwide. The elevated pressure in the pulmonary circulation can lead to various symptoms including limited exercise capacity and dyspnoea on exertion. Chronic elevated pressure may ultimately result in right-sided heart failure and premature death.

Transthoracic echocardiography is the cornerstone for screening in all patients suspected of PH.

PAH caused by an ACVRL1 mutation is found in significantly younger patients and has significantly shorter survival, despite adequate therapy. No data exists on the prognosis of patients with PAH and ENG mutations. It is noteworthy that ACVRL1 mutation carriers may develop severe PAH without any clinical evidence of HHT because of the early development of PAH in these patients.

Conclusion

The association between hereditary haemorrhagic telangiectasia and pulmonary arterial hypertension is rare (< 1%). In this case study of an 11-year-old boy with a history of syncope in his childhood and the tragic sudden cardiac death of his younger sister due to severe PAH, the family’s journey led to the diagnosis of the rare cause of PAH which is HHT.

This case underscores the importance of considering genetic factors and familial history when evaluating unexplained causes of severe PAH. Here we have described a rare cause of pulmonary hypertension- hereditary haemorrhagic telangiectasia as a result of an ACVRL1 mutation. We have also described the clinical challenges of treating these two conditions together.