Incontinentia Pigmenti - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Incontinentia pigmenti is also known as Bloch-Siemens-Sulzberger syndrome. It is more commonly seen in females. The symptoms of this disease may first appear in early infancy and may continue throughout childhood until adulthood. This condition affects other body parts such as teeth, hair, eyes, fingernails, and the central nervous system. This disease may also significantly affect brain function. The affected individuals may show signs of developmental delay and intellectual disability. It is an X-linked autosomal dominant type of disease.

What Is an X-Linked Dominant Disorder?

A gene is the basic structural and functional unit of heredity. Genes are made up of DNA (deoxyribonucleic acid). DNA is present in the nucleus of the cell. The DNA molecules are tightly packed or coiled in a thread-like pattern known as the chromosome. The structure of chromosomes is histone proteins filled with DNA strands. Histone proteins provide structural support to the chromosomes. Each chromosome has a pair of X and Y chromosomes known as the sex chromosomes. Sex chromosomes are responsible for determining the sex of an individual. Females have two x chromosomes, and males have X and Y chromosomes.

In this type of disorder, the gene associated with the disease is on the X chromosome.

This disease is caused by mutations in the genes present on the X-chromosome. Affected females have a 50 % chance of transmitting this disease to the fetus at conception. An affected male would transfer this disease to his sons, not his daughters.

What Causes Incontinentia Pigmenti?

Mutations (changes in the gene structure or DNA sequence) in the IKBKG gene (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma gene) are responsible for this disease.

The nuclear factor kappa-B plays a vital role in forming ectodermal tissues, including the skin, hair, teeth, and sweat glands. It also protects the cells from specific signals that cause them to self-destruct. When there are mutations in the IKBKG gene, all the functions of this gene are affected, resulting in the disease.

What Are the Signs and Symptoms of Incontinentia Pigmenti?

Incontinentia pigmenti affects the tissues of ectodermal origin, such as the skin, hair, nails, and teeth. It also affects the brain and eyes.

1) Skin Abnormalities Include -

1. Blistering Rashes - Infants may show a rash similar to blisters and boils. This rash further develops into raised wart-like skin growths. They are identical to thick crusts or healing scabs that are pigmented. These lesions may resolve independently but frequently reappear, especially in a fever.

2. Swirling Macular Hyperpigmentation - Hyperpigmentation (brown or gray discoloration of the skin) is seen in children. These patches of discolored skin present in a swirl-like pattern.

3. Linear Hypopigmentation - In adults, there are lines of hypopigmentation on the skin (light-colored skin) on the arms and legs.

2) Teeth Abnormalities - Almost 50% to 70% of individuals with incontinentia pigmenti have developmental defects with their teeth.

1. Delayed eruption of primary (milk) teeth.

2. Changes in the anatomy of the tooth structure (abnormal tooth contours, peg-shaped teeth, tiny teeth, or microdontia).

3. Congenital absence of teeth (missing teeth).

3) Nail Defects - Thick and pitted nails (depressions in the nails) and ridges are present on the nails. Sometimes the nail is absent. In addition, there may be some painful growths under the nails.

4) Hair Problems - Patients may experience patchy hair loss or balding (alopecia). The hair becomes very coarse, and there is a lack of luster.

5)Ocular (Eye) Abnormalities -

1. In severe cases of incontinentia pigmenti, the patient may experience vision loss or blindness.

2. The eyes of the affected individual may be too small or look abnormal. For example, they may be strabismus (cross-eye).

3. Patients may develop cataracts (the eye's lens becomes cloudy, resulting in blurred vision).

6) Nervous System (Brain) Abnormalities - This disease may also affect the brain.

1. The patient may experience uncontrolled seizures (rapid involuntary body movements accompanied by loss of consciousness).

2. There may be a delay in the affected child's development, intellectual disability, and poor motor development.

3. The patient may experience weakness in muscles or muscle spasms (rigidity).

4. Children aged two to four years may exhibit symptoms of ADHD (attention deficit hyperactivity disorder). The common symptoms of this disorder are impulsiveness, hyperactivity, difficulty in focusing on one task, inability to fall asleep, and social problems due to aggressiveness.

How to Diagnose Incontinentia Pigmenti?

1. Molecular genetic testing is recommended to identify the mutations in the IKBKG gene in individuals showing positive signs of the disease.

2. Identification of clinical features is also an essential aspect of diagnosing this disease.

How to Treat Incontinentia Pigmenti?

As this disease is genetic, there is no specific treatment to treat the gene mutations. The condition is managed by treating the symptoms.

1. The skin lesions usually resolve themselves over time, but topical application of steroid creams helps reduce their severity.

2. Anti-epileptic medications are used to control seizures. In addition, muscle spasms may require physical therapy.

3. Alopecia is treated with topical application of medication.

4. Support and education are necessary for patients with developmental problems.

5. Eye problems may require surgery to treat cataracts. Corrective lenses are used to manage decreased vision.

6. The patient needs to visit a pediatric dentist to treat dental problems in children.

7. Genetic counseling is crucial for affected individuals and their families.

What Is the Prognosis of This Disease?

Usually, most patients who do not have severe neurological complications can lead a long healthy life. In addition, skin problems are temporary and resolve over time.

Conclusion:

Incontinentia pigmenti is a rare genetic disorder with a good prognosis. Patients can overcome the problems caused by this disease by reaching out to the health provider as soon as symptoms appear. Symptomatic care is essential in treating this disease. Patients with neurological symptoms may require intensive treatment. This disease can be treated and, in most cases, does not debilitate the patient. Developmental delay and intellectual disability in patients need support and education.