Cardiovascular Abnormalities In Bachmann-Bupp Syndrome

Introduction

What is Bachmann-Bupp Syndrome?

Bachmann-Bupp syndrome (BABS) is a neurodevelopmental rare genetic disorder caused by a mutation in the 3′-end of the ornithine-decarboxylase-1 (ODC1) gene causing the accumulation of the ODC enzymes.¹ This buildup produces a catalytically active enzyme that influences the polyamine pathway necessary for different genesis pathways, including organogenesis, tumorigenesis, glycogenesis, and embryogenesis.² This in turn affects the production of proteins and lipids in the body resulting in phenotypic disorders including:

• Non-congenital alopecia
• Hypotonia 
• Delay in brain development
• Intellectual disability
• Epileptic seizures 
• Growth retardation
• Hypoglycaemia
• Liver dysfunction
• Cardiovascular abnormalities³ 

This eventually affects the integrity and function of vascular endothelial and smooth muscle cells, leading to structural defects and impaired regulation of blood vessel function. In this article, we will be focusing on cardiovascular abnormalities caused by BABS as they can significantly affect the morbidity and mortality of individuals suffering from the disease ,impacting their quality of life.⁴

Cardiovascular abnormalities in Bachmann-Bupp syndrome

The most common types of abnormalities in BABS include congenital heart defects (CHDs), arrhythmias, and vascular anomalies. Diagnosing these conditions would include imaging techniques such as chest X-rays, electrocardiogram (ECG or EKG), cardiac catheterisation, magnetic resonance imaging (MRI) or open-heart surgery. Treatments for these can vary from medications to surgical procedures including cardioversion, catheter ablation or pacemaker to correct abnormal heart rhythms.⁵

Congenital heart defects

There are 3 types of CHD’s in BABS. These include atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), the first being the most common type.⁶

Atrial septal defect

ASD is a result of a defect between the left and right chambers in the heart which results in abnormal blood flow, oxygen-rich blood being transported from left to right atrium. This increases blood pressure from the right side of the heart to ensure oxygen reaches the cells. Increased pressure could strain the heart and lungs leading to heart failure, pulmonary hypertension (increased blood pressure in the lungs), and arrhythmias (irregular heartbeats). This would damage the blood vessels significantly over time. Symptoms would not be obvious with a minor form of ASD but would typically include:

• Fatigue
• Shortness of breath
• Frequent respiratory infections

Ventricular septal defect

Ventricular septal defect (VSD) is an opening within the septum of the heart. When blood is exchanged in the heart, deoxygenated and oxygenated blood mix, straining the heart to deliver oxygen to target cells and decreasing its efficiency. In the case of a large VSD, the following symptoms are present: 

• Heart murmur
• Breathing difficulties
• Fatigue
• Poor weight gain
• Frequent respiratory infections
• Swelling

Patent ductus arteriosus

Patent ductus arteriosus (PDA) occurs in babies when the foetal blood vessel (ductus arteriosus) bypasses the lungs and does not close after birth. This could result in extreme pulmonary blood flow and over-circulation, leading to pulmonary hypertension and heart failure. Symptoms could include: 

• Heart murmurs
• Respiratory distress
• Poor feeding
• Fatigue
• Frequent respiratory infections
• Cyanosis

Arrhythmias

Arrhythmias is another cardiovascular abnormality present in patients suffering from BABS. Arrhythmias is an abnormality in the beating of the heart’s rhythm. It may be too slow, too quick, or irregular and can range from minor to severe.⁷

2 common types of arrhythmias could be present in BABS. These include:

• Bradyarrhythmias: a slower-than-normal heart rate resulting in dizziness, fatigue, shortness of breath, chest pain, and fainting
• Tachyarrhythmia: is the abnormally fast heart rate resulting in a heart rate exceeding 100 beats per minute, leading to various symptoms such as palpitations, dizziness, shortness of breath, chest pain, or fainting

Vascular anomalies

Other cardiovascular abnormalities include:

• Conduction abnormalities: disruption in normal heartbeat contraction rate causing palpitations, dizziness, and difficulty in breathing. More severe forms of this can cause fainting or heart failure⁸
• Vascular anomalies: abnormalities in blood vessel structures, impacting blood flow, causing bleeding or thrombosis. Surgical intervention or endovascular procedures to treat this⁹
• Aortic coarctation: narrowing of the aorta (left subclavian artery), causing increased blood pressure in the upper body and decreased blood flow to the lower body, resulting in hypertension and organ dysfunction. Surgical correction or balloon angioplasty is the procedure conducted to relieve constriction and restore normal blood flow¹⁰
• Pulmonary hypertension: a secondary condition to congenital heart defects like ASD, VSD, or PDA because of increased pressure on pulmonary arteries. Management includes congenital defects and using medications to reduce pulmonary artery pressure¹¹
• Arteriovenous malformations (AVMs): are structures within arteries and veins and if abnormally connected could result in complications such as haemorrhage or stroke based on location in the body. Surgical resection, endovascular embolisation, or radiosurgery are treatments to manage abnormal blood flow and prevent further complications¹²

Management

A multi-disciplinary team (MDT), including cardiologists, geneticists, and other specialists, are required to treat BABS. The severity of the condition determines how to approach and treat the patients’ conditions. There are 3 main forms of treatment plans for patients with this condition including medical management, surgical interventions, and long-term care.

Treatment strategies depend on the specific abnormalities present and their severity.

Medical management includes a pharmacological treatment plan that uses medications such as antiarrhythmics, diuretics, and antihypertensives to manage arrhythmias, reduce fluid overload in heart failure, and control blood pressure. Surgical interventions, such as congenital heart defect repair or the implantation of pacemakers or defibrillators, are also required to regulate heart rhythm in patients.

Long-term care including cardiac rehabilitation and genetic counselling for education of the condition and informing families of potential prenatal diagnosis, inheritance patterns and recurrence risks of the condition respectively.

FAQs 

How are cardiac abnormalities in Bachmann-Bupp Syndrome (BABS) different from other congenital heart diseases?

• Cardiac abnormalities can include many abnormalities such as ASD, VSD and PDA
• Congenital heart disease causes a single defect
• Imaging techniques required to ensure correct treatment plan formed for patients⁸

What complications can BABS lead to?

• Cardiovascular abnormalities in BABS include heart failure, arrhythmias, and pulmonary hypertension
• Untreated symptoms can cause complications and exacerbate symptoms⁵

What Diagnostic tools to assess the abnormalities in BABS and how do they improve patient care?

Echocardiography (providing detailed images of the heart’s structure), cardiac MRI (anatomical and functional of the heart) and genetic testing (identify underlying genetic mutations).⁵

How does managing cardiac abnormalities in BABS differ in paediatric to adult patients?

• Paediatric patients: monitoring growth and development with congenital defects, surgical interventions, and catheter-based procedures
• Adults: long-term effects and complications of congenital defects and ongoing monitoring of previously treated abnormalities⁵

Summary

There are various forms of cardiovascular abnormalities in Bachmann-Bupp syndrome which can affect the quality of life of patients significantly. Understanding these various forms is crucial to correctly manage and treat patients with these conditions using the advanced technology present. Over time, we will be able to learn more about the pathophysiology of BABS and design patient-specific treatment plans to better treat cardiovascular abnormalities.

Different forms of cardiovascular abnormalities in Bachmann-Bupp Syndrome (BABS) can significantly impact a patient's quality of life. Various forms of these abnormalities need advanced imaging techniques to identify, evaluate and diagnose to ensure the patient receives the right treatment plan. For example, simple medications are used to treat a mild form of the abnormality while surgical interventions are for severe forms.

It is crucial patients are diagnosed at the earliest to avoid further complications of these problems which could in turn affect the quality of their lives. As research into BABS continues, scientists will be better able to understand the pathophysiology of this syndrome and as a result, could be able to find more ways to diagnose this. Ongoing research in this field focuses on therapeutic methods and interventions to improve patient prognosis and management of patients currently suffering from this disease.