What is Dominant Titinopathy?

What is Dominant Titinopathy?

Dominant Titinopathy is when there is only one dominant copy of the disease causing variant of TTN gene from either parent causing this genetic condition. The TTN gene is responsible for making Titin protein, without the proper instructions the production, structure and function of the Titin protein is impacted which causes various cardiac and musculoskeletal diseases.

Related: What is Congenital Titinopathy?

What is Recessive Titinopathy?

Types of Dominant Titinopathy

There are various types of Dominant Titinopathies based on the location, part of the body it affects and the way it manifests. Some of the types of dominant titinopathy are:

• TTN related Dilated Cardiomyopathy (DCM)

• Tibial Muscular Dystrophy

• Distal Cardiomyopathy related to TTN

• TTN related Distal Arthrogryposis

• Hereditary Myopathy with Early Respiratory Failure (HMERF)

What Causes Dominant Titinopathy?

Typically all human beings have 2 copies of healthy TTN gene, in case of Dominant Titinopathy one copy is altered (mutation) making it a disease causing variant that affects the way Titin is produced and functions in the body. In case of Dominant Titinopathy the disease causing gene variants result in shorter titin protein than the normal ones, hence they are called as Truncating TTN variants. There is a 50% chance the baby of a parent with Dominant Titinopathy will get it in each pregnancy.

The exact cause of why these gene mutations happen is not well understood, however many researchers believe certain risk factors can increase the chances of gene mutations in pregnancy ( de novo) and in parents that could be passed down to future generations.

• Use of recreational drugs, alcohol, smoking

• Exposure to certain harmful chemicals, environmental factors like radiation, x-rays that can alter the DNA

• Viral Infections, where the viral DNA integrates into the hosts causing mutations

• Errors in DNA replication during cell division

Dominant Titinopathy Symptoms

Dominant Titinopathy is a progressive disease and based on which part of the body the disease affects the symptoms vary from person to person. Some of the common symptoms are:

• Weakness in arms, legs, neck, trunk among others

• Difficulty in moving the body, limited range of motion

• Stiff joints (curvatures)

• Curved spine (scoliosis)

• Breathing and feeding difficulties (swallowing, chewing, sucking, drinking)

• Heart complications: Enlargement, failure, irregular heartbeat, difficulty pumping blood, palpitations, blackouts.

• Difficulty performing daily tasks - Walking, climbing stairs, exercise

• Excessive fatigue

• Difficulty in sleeping through the night due to laboured breathing

• Frequent falls

• Waddling gait

Dominant Titinopathy Diagnosis

There are different tests through which a doctor can diagnose or confirm Dominant Titinopathy both during pregnancy and after birth.

• During Pregnancy: Anomalies may show up during an ultrasound scan, presence of contractures, abnormal features, less to lack of movements during pregnancy could point to Titinopathy among many other reasons with common symptoms so the doctor would probe more with other tests to confirm the diagnosis. In most cases the diagnosis happens after birth.

• Genetic Testing: In case of fetus, as these are invasive tests so done only if the doctor feels something is not right. The doctor will ask for amniocentesis (drawing out using a needle and testing the amniotic fluid) or using chorionic villus sampling test (tests the cells of placenta) to confirm the diagnosis. After birth, the baby's blood is tested to look for disease causing variant of TTN gene.

• Physical Examination: Right after birth the doctor performs a thorough physical examination to look for any anomalies like low muscle tone, weakness, difficulty breathing, cardiac anomalies, troubled or less movements, among others.

• Ultrasound: Is used both prenatally and after birth of the baby to look functioning of the body - heart, lungs, muscles, etc.

• Muscle Imaging Studies: Studying the impact of the disorder on the muscles using ultrasound, CT scan (computed tomography) and MRI (Magnetic Resonance Imaging ) to help assess the muscle mass, quality, functioning and muscle cross sectional area in detail.

• Sleep Study: Painless test that uses sensors attached to the baby to measure breathing and functioning of the heart, lungs.

• ECG or Electrocardiogram: It uses multiple sensors attached to your child's chest to measure electrical activity that comes up as a graph, doctors look for any cardiac anomalies associated with Titinopathy using ECG.

Dominant Titinopathy Treatment

There is no cure for Dominant Titinopathy but the symptoms can be managed with the help of multiple specialists for breathing, cardiac issues and musculoskeletal issues with physical therapy to an extent. In case of heart failure medications, devices or surgery can help. Surgery is also used for joint changes and contractures to help with movement. All in all the focus for doctors is to help with day to day symptoms and help reduce the rate at which the disease progresses.

Dominant Titinopathy Life Expectancy

Dominant Titinopathy affects each patient differently, the age at which the symptoms appear (mostly in early adulthood), severity and progression also varies greatly with some having serious complications like breathing and cardiac issues while others have manageable symptoms. Given this vast range of possibilities across every patient, predicting life expectancy is difficult, but in ones where the symptoms start in adulthood or later in life and affect lower body muscles (legs)the life expectancy could be closer to normal than ones that begin to show early on.