hypertension and brachydactyly syndrome

Hypertension and Brachydactyly Syndrome (HTNB): A Rare Genetic Disorder

Hypertension and brachydactyly syndrome, also known as Bilginturan syndrome or brachydactyly type E, is a rare genetic disorder characterized by severe salt-independent but age-dependent hypertension. This condition is associated with short stature and a specific form of brachydactyly, which involves the shortening of both phalanges and metacarpals.

Key Features:

• Brachydactyly Type E: A rare form of brachydactyly that affects the hands, characterized by short fingers and toes.
• Severe Salt-Independent Hypertension: High blood pressure that is not dependent on salt intake, but rather increases with age.
• Short Stature: Affected individuals often have short stature compared to their family members.
• Increased Fibroblast Growth Rate: A higher rate of cell growth and division in the body.
• Neurovascular Contact at the Rostral-Ventrolateral Medulla: Abnormal contact between nerves and blood vessels in the brain, leading to altered baroreflex blood pressure regulation.

Consequences:

If left untreated, HTNB can lead to severe consequences, including:

• Recurrent strokes before age 50 years
• High mortality rate due to stroke-related complications

Genetic Basis: HTNB is an autosomal dominant genetic disorder, meaning that a single copy of the mutated gene is sufficient to cause the condition. The phosphodiesterase 3A (PDE3A) gene mutations have recently been associated with HTNB.

References:

• [1] Bilginturan et al. (1973)
• [2] Estimated prevalence less than 1 in 1,000,000
• [3-4] First reported by N. Bilginturan et al.
• [5-6] Characterized by severe salt-independent but age-dependent hypertension and brachydactyly type E
• [7-8] Associated with short stature, increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation, and death from stroke before age 50 years.
• [9-10] Phosphodiesterase 3A (PDE3A) gene mutations associated with HTNB
• [11-12] Brachydactyly - arterial hypertension is a rare genetic brachydactyly syndrome characterized by the association of brachydactyly type E (see this term) with hypertension (due to vascular or neurovascular anomalies) as well as the additional features of short stature and low birth weight (compared to non-affected family members), stocky build and a round face.

Common Signs and Symptoms of Hypertension and Brachydactyly Syndrome

Hypertension and brachydactyly syndrome (HTNB) is a rare genetic disorder characterized by the association of brachydactyly type E with hypertension, as well as additional features such as short stature, low birth weight, stocky build, and round face.

Key Symptoms:

• Brachydactyly Type E: A rare form of brachydactyly, which is a genetic disorder characterized by short fingers.
• Hypertension: High blood pressure that can be severe and age-dependent.
• Short Stature: Individuals with HTNB often have short stature compared to their family members.
• Low Birth Weight: Babies born to individuals with HTNB may have low birth weight.
• Stocky Build: A stocky or muscular build is a common feature in individuals with HTNB.
• Round Face: A round face shape is also associated with HTNB.

Other Possible Symptoms:

• Essential hypertension
• Headaches
• Dizziness
• Chest pain
• Accumulation of fluid under the skin
• Back pain, aches, soreness, or discomfort reduction deformities of the upper limb

Please note that these symptoms may vary in severity and presentation from person to person. A diagnosis of HTNB is typically made based on a combination of clinical evaluation, family history, and genetic testing.

References: [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

Diagnostic Tests for Hypertension and Brachydactyly Syndrome

Hypertension and brachydactyly syndrome (HTNB) is a rare genetic disorder characterized by the association of brachydactyly type E with hypertension. Diagnosing HTNB can be challenging, but various diagnostic tests can help confirm the condition.

• Genetic Testing: Molecular genetic testing is ideal for diagnosing HTNB due to variation in severity and presentation [12]. Genetic testing involves analyzing DNA samples from affected individuals or family members to identify mutations in the PDE3A gene.
• Exome-Based Next-Generation Sequencing (NGS): This test can detect mutations in the PDE3A gene, which is responsible for HTNB. Exome-based NGS is a cost-effective and efficient method for identifying genetic variants [5].
• Clinical Genetic Test: A clinical genetic test offered by Intergen can also be used to diagnose HTNB. This test involves analyzing DNA samples from affected individuals or family members to identify mutations in the PDE3A gene [4].

Other Diagnostic Tests

While not specific to HTNB, other diagnostic tests may be used to support a diagnosis of this condition:

• Physical Examination: A physical examination can reveal brachydactyly type E and other characteristic features of HTNB, such as short stature, low birth weight, stocky build, and round face [14].
• Imaging Studies: Imaging studies, such as MRI or CT scans, may be used to evaluate the presence of neurovascular contact at the rostral-ventrolateral medulla, which is a characteristic feature of HTNB [12].

References

[4] Intergen. Clinical Genetic Test for Brachydactyly-Arterial Hypertension Syndrome.

[5] Fan P. Exome-Based Next-Generation Sequencing with CNV Analysis for Diagnosing HTNB Patients.

[12] Bilginturan syndrome (hypertension and brachydactyly syndrome). Hypertens Res. 2018; 41: 981.

[14] Brachydactyly - arterial hypertension is a rare genetic brachydactyly syndrome characterized by the association of brachydactyly type E with hypertension.

Treatment Overview

The primary focus in treating Hypertension with Brachydactyly (HTNB) or Bilginturan syndrome is to manage the associated hypertension through antihypertensive medication. The goal is to prevent end-organ damage, particularly stroke, which can occur at a young age if left untreated.

Medications Used

According to various studies [3][5][9], treatment mainly focuses on antihypertension medications, including:

• Calcium-channel blockers
• Converting enzyme inhibitors
• Dihydralazine
• Beta-blockers

A combination of two or more drugs is often necessary to control hypertension in patients with this syndrome [5]. Selective beta-1 receptor blockers are also recommended for treatment [3].

Early Intervention

Initiating anti-hypertensive medication early on is crucial, as untreated clinical courses can lead to severe consequences [6]. Early detection and treatment of HTNB can decrease the risk of detrimental end-organ damage and long-term debility.

Recommended Drugs

For childhood hypertension, recommended drugs are provided for ages 1 to 17 years [12].

Global Prevalence and Treatment Importance

The global prevalence of hypertension is high, and among nonpregnant adults in the United States, treatment of hypertension is the most common reason for office visits and for the use of chronic prescription medications [14]. The intensity of antihypertensive drug therapy has been recognized as being more important for preventing end-organ damage.

References

[3] by P Fan · 2020 · Cited by 13 — Treatment mainly focuses on antihypertension. General medications, including calcium-channel blockers, converting enzyme inhibitors, dihydralazine, and beta-...

[5] by P Fan · 2020 · Cited by 13 — Litwin et al. reported that combined therapy with 2 or more drugs is usually needed to control hypertension in patients with this syndrome.

[6] Dec 19, 2022 — Anti-hypertensive medication should be initiated early given the untreated clinical course of this disease.

[9] Importantly, hypertension with brachydactyly occurs worldwide. Once the diagnosis is made, we recommend treatment of all individuals with stage 2 hypertension...

[12] Affected individuals with autosomal-dominant hypertension with brachydactyly syndrome develop severe progressive hypertension and, if left untreated, develop stroke by age <50 years.

[14] INTRODUCTION — . The global prevalence of hypertension is high, and among nonpregnant adults in the United States, treatment of hypertension is the most common reason for office visits and for the use of chronic prescription medications.

Differential Diagnosis of Hypertension and Brachydactyly Syndrome

Hypertension and brachydactyly syndrome (HTNB), also known as Bilginturan syndrome, is a rare autosomal dominant disorder characterized by the combination of hypertension and brachydactyly type E. When diagnosing HTNB, it's essential to consider other conditions that may present with similar symptoms.

Possible Differential Diagnoses:

• Turner syndrome: A genetic condition that affects females, characterized by short stature, heart defects, and infertility.
• Brachydactyly type E: A rare congenital disorder that affects the hands, causing them to be shorter than usual.
• Hypertension of unknown aetiology: High blood pressure with an unknown cause.

Key Features to Consider:

• Short stature
• Heart defects
• Infertility (in females)
• Brachydactyly type E
• Age-dependent and salt-independent hypertension

Diagnostic Approach:

To diagnose HTNB, it's crucial to consider the patient's medical history, perform a physical examination, and conduct genetic testing. The PDE3A gene mutation is a key indicator of HTNB.

• Genetic testing for PDE3A mutations
• Physical examination to assess brachydactyly type E and other symptoms
• Medical history review to identify hypertension and other related conditions

References:

[4] PDE3A gene screening improves diagnostics for patients with Bilginturan syndrome (HTNB), Hypertension ... [5] This disorder should be included in the differential diagnosis of patients with short stature and hypertension of unknown aetiology. [6] PDE3A gene screening improves diagnostics for patients with Bilginturan syndrome (hypertension and brachydactyly syndrome), Hypertension ... [9] Background: Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder ...