Incontinentia pigmenti
Encyclopedia
Incontinentia Pigmenti (also known as "Bloch–Siemens syndrome," "Bloch–Sulzberger disease," "Bloch–Sulzberger syndrome" "melanoblastosis cutis," and "naevus pigmentosus systematicus") is a genetic disorder
that affects the skin, hair, teeth, nails, and central nervous system. It is named due to its microscopic appearance.
s evolve through characteristic stages:
Alopecia
, hypodontia
, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.
Discolored skin is caused by excessive deposits of melanin
(normal skin pigment
).
Most newborns with IP will develop discolored skin within the first two weeks.
The pigmentation involves the trunk
and extremities
, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines.
The discoloration sometimes fades with age.
Neurological problems can include: cerebral atrophy
, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex.
About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, mental retardation, and seizures.
They are also likely to have visual problems, which can include: crossed eyes, cataracts, and severe visual loss.
Dental problems are common, and include missing or peg-shaped teeth - patients with IP often keep milk teeth into adult life.
Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia
and supernumerary nipples.
Skeletal and structural anomalies can occur in approximately 14% of patients, including:
Somatic asymmetry,
Hemivertebrae,
Scoliosis
,
Spina bifida
,
Syndactyly
,
Acheiria (congenital absence of the hands - note: other limbs may be affected),
Ear anomalies,
Extra ribs,
Skull deformities,
Primary pulmonary hypertension,
and Cardiopulmonary failure
gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically.
In addition, females with IP have skewed X-chromosome
inactivation; testing for this can be used to support the diagnosis.
Many people in the past were misdiagnosed with a second type of IP, called IP2.
This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti achromians
).
This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation.
It is NOT inherited.
It does not inolve skin stages 1 or 2.
33-50% of patients have multisystem involvement — eye, skeletal, and neurological abnormalities.
Its chromosomal locus is at Xp11, not Xp28.
, prenatal testing, and preimplantation genetic diagnosis
is available.
In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die around the time of birth so the X-inactivation is extremely skewed.
IP is caused by mutations in a gene called NEMO (NF-kappaB essential modulator).
dermatologist in 1926 and Marion Sulzberger
, an American
dermatologist in 1928.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that affects the skin, hair, teeth, nails, and central nervous system. It is named due to its microscopic appearance.
Presentation
The skin lesionLesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s evolve through characteristic stages:
- blistering (from birth to about four months of age),
- a wartWartA wart is generally a small, rough growth, typically on a human’s hands or feet but often other locations, that can resemble a cauliflower or a solid blister. They are caused by a viral infection, specifically by human papillomavirus 2 and 7. There are as many as 10 varieties of warts, the most...
-like rash (for several months), - swirling macular hyperpigmentationHyperpigmentationIn dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
(from about six months of age into adulthood), followed by - linear hypopigmentationHypopigmentationHypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.-Treatments:...
.
Alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
, hypodontia
Hypodontia
In dentistry, hypodontia is the condition at which the patient has missing teeth as a result of their failure to develop. Hypodontia describes a situation where the patient is missing up to 6 teeth, excluding the 3rd molars. Missing third molars occur in 9-30% of population...
, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.
Discolored skin is caused by excessive deposits of melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
(normal skin pigment
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
).
Most newborns with IP will develop discolored skin within the first two weeks.
The pigmentation involves the trunk
Torso
Trunk or torso is an anatomical term for the central part of the many animal bodies from which extend the neck and limbs. The trunk includes the thorax and abdomen.-Major organs:...
and extremities
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines.
The discoloration sometimes fades with age.
Neurological problems can include: cerebral atrophy
Cerebral atrophy
Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means loss of cells. In brain tissue, atrophy describes a loss of neurons and the connections between them...
, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex.
About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, mental retardation, and seizures.
They are also likely to have visual problems, which can include: crossed eyes, cataracts, and severe visual loss.
Dental problems are common, and include missing or peg-shaped teeth - patients with IP often keep milk teeth into adult life.
Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
and supernumerary nipples.
Skeletal and structural anomalies can occur in approximately 14% of patients, including:
Somatic asymmetry,
Hemivertebrae,
Scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
,
Spina bifida
Spina bifida
Spina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through...
,
Syndactyly
Syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
,
Acheiria (congenital absence of the hands - note: other limbs may be affected),
Ear anomalies,
Extra ribs,
Skull deformities,
Primary pulmonary hypertension,
and Cardiopulmonary failure
Diagnosis
The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKGIKBKG
NF-kappa-B essential modulator also known as inhibitor of nuclear factor kappa-B kinase subunit gamma is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28...
gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically.
In addition, females with IP have skewed X-chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
inactivation; testing for this can be used to support the diagnosis.
Many people in the past were misdiagnosed with a second type of IP, called IP2.
This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti achromians
Incontinentia pigmenti achromians
Incontinentia pigmenti achromians is a cutaneous condition characterized by various patterns of bilateral or unilateral hypopigmentation following the lines of Blaschko....
).
This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation.
It is NOT inherited.
It does not inolve skin stages 1 or 2.
33-50% of patients have multisystem involvement — eye, skeletal, and neurological abnormalities.
Its chromosomal locus is at Xp11, not Xp28.
Genetics
IP is inherited in an X-linked dominant manner. IP is lethal in most, but not all, males. A female with IP may have inherited the IKBKG mutation from either parent or have a new gene mutation. Parents may either be clinically affected or have germline mosaicism. Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception; however, most affected male conceptuses miscarry. Thus, the expected ratio for liveborn children is 33% unaffected females, 33% affected females, and 33% unaffected males. Genetic counselingGenetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
, prenatal testing, and preimplantation genetic diagnosis
Preimplantation genetic diagnosis
In medicine and genetics pre-implantation genetic diagnosis refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis...
is available.
In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die around the time of birth so the X-inactivation is extremely skewed.
IP is caused by mutations in a gene called NEMO (NF-kappaB essential modulator).
History
This disorder was first reported by Bruno Bloch, a GermanGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
dermatologist in 1926 and Marion Sulzberger
Marion Sulzberger
Marion Sulzberger was an American physician known for his major contribution to dermatology.- References :...
, an American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
dermatologist in 1928.