Hypertension and brachydactyly syndrome

Overview

Hypertension and brachydactyly syndrome (HTNB), also known as Bilginturan syndrome, is a rare genetic disorder characterized by the early onset of severe high blood pressure (hypertension) and brachydactyly (shortening of the fingers and toes). First described in a Turkish family by Dr. Bilginturan, the syndrome presents in childhood or adolescence and carries a high risk of stroke and other cardiovascular complications if left untreated. Despite the skeletal abnormalities, patients typically have normal intelligence and development.

Causes

Hypertension and brachydactyly syndrome is caused by mutations in the PDE3A gene (phosphodiesterase 3A). This gene is involved in regulating the levels of cyclic AMP (cAMP), a molecule important in many cellular signaling pathways, including those controlling vascular smooth muscle contraction. Mutations in PDE3A lead to abnormal vascular tone and premature vascular remodeling, contributing to the development of hypertension. The condition is inherited in an autosomal dominant manner, meaning only one mutated copy of the gene is sufficient to cause the disorder.

Symptoms

HTNB syndrome presents with a combination of cardiovascular and skeletal symptoms, typically in childhood or early adolescence. Key clinical features include:

• Early-onset severe hypertension: Often resistant to standard treatments

• Brachydactyly: Shortened middle phalanges of the fingers and toes, usually most noticeable in the fourth and fifth digits

• Normal growth and intelligence: Unlike some other syndromes with skeletal abnormalities

• Increased risk of cerebrovascular events: Such as stroke, often occurring in young adulthood if hypertension is not adequately managed

• Possible signs of cardiovascular damage over time (e.g., left ventricular hypertrophy)

Diagnosis

Diagnosis is made based on clinical findings, family history, and genetic testing. Diagnostic steps include:

• Blood pressure monitoring: Persistent elevation at a young age

• Physical examination: Detection of brachydactyly, especially of the fourth and fifth digits

• Radiographic imaging: X-rays of the hands and feet to confirm shortening of specific phalanges

• Genetic testing: Identification of mutations in the PDE3A gene confirms the diagnosis

• Family history evaluation: Often reveals multiple affected individuals in successive generations

Treatment

There is no cure for HTNB syndrome, but the primary goal of treatment is to aggressively manage blood pressure to prevent life-threatening complications. Treatment options include:

• Antihypertensive medications: Often requires multiple drug classes, such as ACE inhibitors, calcium channel blockers, and beta-blockers

• Lifestyle modifications: Including low-sodium diet, regular physical activity, and weight management

• Regular monitoring: Of blood pressure and cardiovascular health through echocardiograms and other tests

• Genetic counseling: For affected individuals and their families

There is currently no specific treatment to correct the skeletal abnormalities, but they typically do not cause functional problems.

Prognosis

The prognosis of hypertension and brachydactyly syndrome depends largely on the effectiveness of blood pressure control. Without treatment, the risk of early stroke and cardiovascular complications is high. With early diagnosis and rigorous management of hypertension, individuals can lead relatively normal lives. The skeletal abnormalities are usually not progressive and do not significantly impair function or quality of life.