Troyer Syndrome - Cause, Clinical Features, Diagnosis, and Treatment

Introduction:

Troyer syndrome is a rare genetic disorder that belongs to hereditary spastic paraplegias, which are a group of genetic disorders characterized by stiffness and weakness in the lower extremities, which becomes severe with time. Hereditary spastic paraplegias are of two forms which are pure and complex; Troyer syndrome belongs to the complex type. Pure hereditary spastic paraplegias affect the lower extremities, and complex hereditary spastic paraplegias affect the upper and lower limbs, brain function, and the peripheral nervous system (the nerves that come out of the brain and spinal cord). Individuals with Troyer syndrome undergo progressive degeneration (loss of function) of motor neurons (nerves that are responsible for both voluntary and involuntary movements) and muscle cells throughout their life. The affected individuals are bound to a wheelchair. Individuals with Troyer syndrome have a normal life span.

What Is Troyer Syndrome?

Troyer syndrome is a type of inherited genetic disorder that occurs due to a mutation of the SPART (spartin) gene that causes progressive loss of muscle functions, and the severity increases as the person ages. Treatment is aimed at reducing the discomfort and is mainly supportive.

What Is the Cause of Troyer Syndrome?

Troyer syndrome occurs due to a mutation in the SPART gene, also called spastic paraplegia gene (SPG20), which is inherited in an autosomal recessive pattern in which the mutated gene is present in both the parents and is passed down to the child that has two copies of the mutated gene. The parents carry one mutated gene each and are not affected by the condition and are called carriers. The features of this gene are:

• The SPART gene is located on chromosome 13.

• The SPART gene provides instructions for the formation of a protein called spartan.

• The spartan protein is found in the nervous system and in the body tissues.

• The spartin protein plays an important role in cell functioning, breaking down proteins and transferring them from the membranes of cells into the cell.

A mutation in the SPART gene results in a lack of spartan proteins, therefore, affecting its function and causing Troyer syndrome.

What Are the Clinical Features of Troyer Syndrome?

The clinical features may vary among people, and some may be affected mildly. The clinical features can be present at birth, and the severity increases as the child ages.

At birth, the features include:

• Low birth weight.

• Macrocephaly (large head).

• Triangular face.

• Difficulty feeding.

The features of Troyer syndrome are:

• Spasticity or stiffness of lower extremities (legs).

• Muscle weakness which becomes worse as time passes.

• Muscle wasting of upper and lower extremities (hands and legs).

• Paraplegia (inability to move).

• Short stature.

• Delay in development.

• Difficulty in walking.

• Difficulty in speech and learning.

• Mood swings.

• Hyperreflexia (overactive reflexes of muscles of the body).

• Choreoathetosis (uncontrollable movements).

• Skeletal abnormalities such as valgus knees (knees that are turned outwards).

• Drooling.

What Are the Other Names for Troyer Syndrome?

The other names for Troyer syndrome are:

• Autosomal recessive hereditary spastic paraplegia.

• Cross-McKusick syndrome.

• Spastic paraplegia 20, autosomal recessive.

What Is the Diagnosis of Troyer Syndrome?

The diagnosis of Troyer syndrome includes:

• Diagnosis can be made with the help of clinical features such as stiff muscles, muscle wasting, difficulty in walking, speech, and learning, and positive family history.

• Prenatal molecular genetic testing, which is done during pregnancy, reveals a mutation in the SPART gene.

• Preimplantation genetic testing can be done in the case of in vitro fertilization (IVF) which reveals a mutation in the SPART gene.

• Molecular genetic testing shows a mutation in the SPART gene. Molecular genetic testing can be single-gene testing or by a multigene panel.

  1. Single-gene testing is done to identify changes in one gene, such as small deletions, insertions, or duplications.

  2. Multigene panel testing is done to identify changes in several genes.

• Magnetic resonance imaging (MRI) of the brain shows abnormal white matter, especially in the temporoparietal periventricular area (an area in the brain where fluid-filled spaces called ventricles contain nerve fibers at the posterior and superior junction of the brain).

What Is the Differential Diagnosis of Troyer Syndrome?

The differential diagnosis of Troyer syndrome is:

• Silver-Russell Syndrome: A genetic disorder that causes slow growth, and due to this, the newborns have low birth weight and have difficulty putting on weight. This condition occurs due to abnormalities in the growth-regulating genes.

• Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): A rare genetic disorder that affects the muscles. Individuals are characterized by abnormal stiffening of muscles and reduced sensation in the extremities. This condition occurs due to mutation in the SACS (sacsin molecular chaperone) gene.

What Is the Treatment of Troyer Syndrome?

There is no cure or specific treatment for Troyer syndrome. Symptomatic treatment includes:

• Use of antispasmodic drugs like Lioresal to treat muscle stiffness. Other drugs that can be used are Botulinum A and B toxin injections and Tizanidine.

• Physical therapy to improve muscle movements.

• Occupational therapy to improve daily life activities.

• Speech therapy to improve learning and speech.

• Use of assisted devices to help in walking.

• Use of ankle-foot orthotics to help stabilize joints and improve walking.

• Use of antidepressants to deal with mood swings.

• Use medications such as Oxybutynin, Mirabegron, or Botox to treat urinary urgency.

• Affected individuals who are able to walk should avoid the use of Dantrolene (direct-acting skeletal muscle relaxant.) which can affect mobility.

• Genetic counseling should be given to the affected individuals and families as they have a risk of passing down the syndrome to the next generation.

Monitoring should be done every six to twelve months and should involve assessing swallowing difficulties to avoid aspiration, psychiatric assessment, developmental assessment, and orthopedic assessment.

Conclusion:

Troyer syndrome is a genetic disorder that mainly affects muscles and most individuals are bound to wheelchairs for lifelong and have a normal lifespan. Individuals with Troyer syndrome and family members should receive genetic counseling since it is inherited in an autosomal recessive pattern. The couple who are carriers have a 25 percent risk of transmitting the syndrome to the child, a 50 percent risk of being carriers by their children, and the other 25 percent of children may have normal genes and are not affected by this condition.