What is Recessive Titinopathy?

What is Recessive Titinopathy?

Recessive Titinopathy is a musculoskeletal disorder that affects the structure and function of many different parts of the human body caused by two copies of the disease causing variants of the TTN gene, one from each parent. The symptoms or muscle weakness could begin to show very early -prenatally, at birth or during early childhood but in some cases it could manifest anywhere between later childhood to early adulthood.

Related: What is Congenital Titinopathy?

What is Dominant Titinopathy?

Causes of Recessive Titinopathy?

Humans typically have 46 chromosomes or 23 pairs of chromosomes of which 22 pairs are autosomes (they are common to both the genders) and 1 pair of sex chromosomes (XX females, XY males). Recessive titinopathy is autosomal inheritance, meaning the TTN genes are located in the autosomes so affects both genders alike.

Recessive titinopathy needs both the parents to pass on the copy of disease causing variant of TTN gene to the child. In some cases the child may be only a carrier or may not be affected at all based on what is passed on from the recessive titinopathy carrier parents.

• Scenario 1: 25% chance the baby will get recessive titinopathy, 1 copy of affected TTN gene from each parent leaving no good TTN gene for the body to make enough titin.

• Scenario 2: 50% chance the baby will be a recessive titinopathy carrier, 1 good copy of TTN gene from one parent and 1 faulty copy of TTN gene from the other parent. The baby is unaffected by the faulty gene but becomes a carrier.

• Scenario 3: 25% chance the baby will be healthy with both good copies of TTN gene inherited from the recessive titinopathy parents as a result is not a carrier of the disease either.

Types of Recessive Titinopathy

There are different types of recessive titinopathies based on the location, part of the body it affects and the way it manifests. There also could be versions of this disorder yet to be identified. Some of the types of recessive titinopathy are:

1. Congenital Titinopathy

2. Autosomal recessive Tibial Muscular Dystrophy (TMD)

3. Titin related Limb Girdle Muscular Dystrophy R10

4. Salih Myopathy or Early onset myopathy with fatal cardiomyopathy

5. Emery Dreifuss like Muscular Dystrophy

6. Early Adult Onset Recessive Distal Titinopathy

7. Distal Arthrogryposis (one caused by mutation to TTN gene)

8. Autosomal recessive TTN related Dilated Cardiomyopathy (DCM)

9. TTN related Arthrogryposis Multiplex Congenita

Symptoms of Recessive Titinopathy

The symptoms vary quite a bit across patients, with some having a milder version of recessive titinopathy that remains fairly stable over the years while the others having a severe form that could progress at a very rapid rate. Some of the common symptoms of Recessive Titinopathy are:

• Muscle weakness: Difficulty in moving different body parts like arms, legs, head, neck among others

• Difficulty in moving facial muscles, unable to make or control facial expressions or have droopy eyelids

• Bone and Joint changes or stiffness (contractures)

• Spinal changes causing scoliosis, side curvature of spine

• Changes in the shape of the chest

• Feeding difficulties due to weak muscles - chewing, sucking, swallowing

• Breathing difficulties due to weak chest muscles causing coughing and laboured breathing that is more pronounced at night

• Heart enlargement, failure, irregular heartbeat, abnormal heart, difficulty in pumping blood is commonly seen in patients with recessive titinopathy.

Diagnosis of Recessive Titinopathy

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

• During Pregnancy: During an ultrasound scan your doctor will look for any anomalies (also at anomaly scan), presence of contractures, abnormal features, less to lack of movements during pregnancy could point to Titinopathy among many other possible causes so the doctor would ask for other tests to confirm the diagnosis. In most cases the diagnosis happens after birth.

• Genetic Testing: During pregnancy a doctor would ask for these invasive tests only if they absolutely feel something is not right. The doctor would either do an amniocentesis (drawing out using a needle and testing the amniotic fluid) or a 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 variants 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, 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.

• 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 anomalies associated with Recessive Titinopathy using ECG.

• Muscle Imaging Studies: Studying the impact of the disorder on the muscles using ultrasound, CT scan (computed tomography) and MRI (Magnetic Resonance Imaging ) to 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 and lungs.

Treatment of Recessive Titinopathy

There is no specific treatment or cure for Recessive Titinopathy but based on the type and severity of the disease, the healthcare provider can help manage the symptoms using physical therapy, support breathing (specialists), treat cardiac anomalies to ease the symptoms. Your child may need to see multiple specialists throughout their life based on their condition and extent of severity.

Recessive Titinopathy Life Expectancy

Recessive Titinopathy affects no two individuals alike, some may experience mild forms of it which could be stable over years and lead a fairly normal life while the others may need life long care and support from multiple healthcare specialists. In patients with severe breathing difficulties and cardiac anomalies, the life expectancy reduces as the disease progresses. Based on the severity of the disease there are varying possibilities making it very difficult to predict life expectancy of someone with Recessive Titinopathy.