Incontinentia Pigmenti Achromians or Hypomelanosis of Ito

Incontinentia pigmenti achromians disorder was first described in 1951. It is more commonly called as Hypomelanosis of Ito (HI). It is a cutaneous disorder where the skin loses its pigmentation. It is seen in form of either unilateral or bilateral hypopigmentation.

Incontinentia pigmenti achromians or Hypomelanosis of Ito occur when there is loss of melanin pigment from the epidermis of the skin resulting in hypomelanosis (less of skin pigmentation). It is present as characteristic whorled hypochromic skin lesions. The skin changes are seen right from birth. It often shows its systemic effects beyond the skin and affects other organ systems such as the central nervous system, ocular and musculoskeletal system. Since it is a group of disorders, hence it is termed as syndrome. Incontinentia pigmenti achromians or Hypomelanosis of Ito is mainly attributed to different types of underlying genetic changes. It is not clear whether it is inherited or acquired.

Incontinentia pigmenti achromians is often referred to as Hypomelanosis of Ito or Pigmentary mosaicism hypopigmentation. It occurs due to difference in the cells which have genetic changes as compared to the remaining cells which lack abnormalities and are normal.

Incontinentia pigmenti achromians or Hypomelanosis of Ito is caused due to underlying genetic changes. Most of the cases are of de novo (spontaneous) occurrence since it said to occur after conception or post-zygotically.

There is chromosomal defect in the form of mosaicism, that is any chromosome or part of chromosome may be involved in undergoing abnormality. There can be duplication, point mutation in the gene responsible for pigmentation. Autosomal and sex chromosome translocations, deletions, duplications and triploidy/tetraploidy might also be present.

It is believed that some regions of chromosome 9, 15, and X [9q33-ter, 15q11-q13, Xp11], can be involved in incontinentia pigmenti achromians syndrome. Autosomal duplications and deletions might occur in chromosomes 7, 12, 13, 14, 15, and 18. A number of Incontinentia pigmenti achromians or Hypomelanosis of Ito patients do not possess the same chromosome composition leading to chromosomal mosaic pattern. This pattern can lead to two cell lineages which results in hypopigmented and hyperpigmented patterns of skin.

Current research indicates that Incontinentia pigmenti achromians or Hypomelanosis of Ito is mainly caused due to random X-inactivation associated with X-linked disorders. The specific gene/s which undergoes a balanced translocation is on Xp21.2.

The earlier the genetic variation or chromosomal changes occur, the more number of somatic cells are affected. The extent of the skin lesions and severity depends on the number of cells carrying the genetic change as compared to the cells which are normal and their distribution. A number of abnormalities are present such as chromosomal changes, genetic changes or epigenetic mutations.

The following symptoms are seen to be associated with Incontinentia pigmenti achromians or Hypomelanosis of Ito:

• Unusual patches of light colored skin
• Neurological problems such as seizures
• Scoliosis such as the abnormal curvature of the spine
• Eyes are crossed
• Problems with hearing
• Increased body hair
• Cardiac abnormalities
• Dental malformations where the teeth development is slow, or misshaped. There is increased tooth decay.
• Problems with nails (such as small nails or nails are absent) and discoloration of hair
• There is problem with development of body where one part of body develops faster than the other part.

There is no such treatment for Incontinentia pigmenti achromians or Hypomelanosis of Ito.

• Partial seizures can be treated with specific anti-convulsants. However, nearly 30% patients suffering from Incontinentia pigmenti achromians or Hypomelanosis of Ito do not respond to this treatment and can be considered for respective epilepsy surgery, ketogenic diet and vagal nerve stimulation.
• Topical depigmentation creams such as hydroquinone, corticosteroids and kojic acid can be applied for photoprotection of the hypopigmented areas.
• The child with Incontinentia pigmenti achromians or Hypomelanosis of Ito may be referred for early intervention. If there are developmental delays then child may require educational support as well.
• Conditions such as cataract and cleft palate can be surgically treated.
• The leg-length problem to be corrected through surgery or correction of shoe height.
• There are no diet restrictions in Incontinentia pigmenti achromians or Hypomelanosis of Ito.

There is no drug therapy for Incontinentia pigmenti achromians or Hypomelanosis of Ito; hence, emphasis is on management of the syndrome. Further, the symptoms of Incontinentia pigmenti achromians or Hypomelanosis of Ito vary from patients to patient and thus, the management also varies. Hence, it is important that the patient and their caregiver adopt some coping mechanisms to deal with the syndrome. The coping strategies are as follows:

• Patients suffering from Incontinentia pigmenti achromians or Hypomelanosis of Ito should be taught to take care of their teeth and eyes.
• Adults with learning disabilities require life-long nursing support.
• Behavioral therapy may be helpful for people with Incontinentia pigmenti achromians or Hypomelanosis of Ito.
• Occupational and speech therapy is also helpful to Incontinentia pigmenti achromians or Hypomelanosis of Ito patients.
• The different types of therapies are given to the patient per week for some months to years. If such therapies are started early it leads to positive outcome in the patients.

The outcome depends on the severity of Incontinentia pigmenti achromians or Hypomelanosis of Ito. Some cases of incontinentia pigmenti achromians have less clinical manifestations and are benign; while other cases may have profound symptoms such that it may lead either to the infant mortality or a poor prognosis.

Incontinentia pigmenti achromians or Hypomelanosis of Ito is a rare genetic syndrome; hence, there is limited epidemiological data available. It is the third most common neurocutaneous disease. There is no preference to any race. The male to female ratio is 1:1.2. The extent of occurrence of symptoms appears to be same in both genders. Nearly, 54% of Incontinentia pigmenti achromians or Hypomelanosis of Ito is detected at birth, while 70% of it is diagnosed during first year of life.

The genetic defects which show systemic effects leading to complications in Incontinentia pigmenti achromians or Hypomelanosis of Ito are as follows:

• Cerebral malformations which lead to seizures
• Risk of mental retardation and autism which leads to learning disability
• Deterioration of neurocognitive skills
• Ophthalmic complications like problems to vision
• Complications affecting the bladder, endocrine and renal system
• Presence of various benign and malignant tumors
• The presence of craniofacial malformations of the cleft lip and palate which interferes with feeding and leads to speech problems
• Presence of clubbed feet
• Emotional disturbance due to problems with physical appearance
• Problems in walking due to scoliosis.

The doctor first performs physical examination and records medical history. Due to a number of organ systems being affected, the diagnosis involves examination of different organs too.

• Diagnosis of the skin lesions by means of Wood’s lamp examination
  • Patterned pigmented changes of the skin and are lighter in color than surrounding areas
  • Systemic streaks
  • Patches or whorl-like hypopigmented macules occurring on any part of the body
  • Swirled patterns of color changes present on the trunk and linear patterns down the legs and arms. These are called as Blaschko’s lines. The cause of these lines is not understood.
  • As one ages the hypopigmented lesions become more noticeable with age.
• Along with the skin changes, the neurological and ophthalmic changes are also examined by means of central nervous system imaging using MRI scan and complete ophthalmic examination.
• Neurological exam to assess the extent of neurological problems such as seizures.
• Audiology and Echocardiogram is performed
• Ultrasound of other organs are also done
• General biochemical tests, CBC test and urinalysis is performed.
• Cytogenetic analysis, a genetic testing, is done to determine the chromosomal aberrations. These tests reveal both the type and extent of chromosomal alterations. PCR analysis cannot be performed since the exact gene involved in pathogenesis is not known.
• Skin biopsy is also done to aid in further confirmation.

There is no definitive test to diagnose Incontinentia pigmenti achromians or Hypomelanosis of Ito, since the symptoms vary from patients and there is no homogeneity. Hence, a number of related tests are done to confirm the diagnosis of Incontinentia pigmenti achromians or Hypomelanosis of Ito.

Incontinentia pigmenti achromians or Hypomelanosis of Ito cannot be prevented. Only in case of married women suffering from mild incontinentia pigmenti achromians and is expecting, there are chances that the offspring may be born with the syndrome. To prevent such cases, parents should be counseled to abort the child. Counseling of both parents is important.

Incontinentia pigmenti achromians or Hypomelanosis of Ito is a rare genetic disorder. Till date no research has been able to indicate a definite genetic or chromosomal alteration associated with its pathogenesis. Many people are not aware of this neuro-cutaneous disorder. Hence, it is important to create awareness regarding this disorder.

Also Read:

• What is Kojic Acid Used For?|Does Kojic Acid Work & What are its Side Effects?
• Melasma or Chloasma or Mask of Pregnancy: Causes, Location, Types, Treatment, Prevention
• Darken Skin or Hyperpigmentation: Causes, Symptoms, Treatment- Daily Exercise, Medication
• Cancer Pain: Causes, Symptoms, Treatment, Management