| Incontinentia pigmenti |
| Classification and external resources |
| ICD-10 |
Q82.3 |
| ICD-9 |
757.33 |
| OMIM |
308300 |
| DiseasesDB |
29600 |
| MedlinePlus |
001583 |
| eMedicine |
article/1114205 article/1176285 |
| MeSH |
D007184 |
Incontinentia Pigmenti (also known as "Bloch–Siemens syndrome,"[1] "Bloch–Sulzberger disease,"[2] "Bloch–Sulzberger syndrome"[1] "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.
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Contents
- 1 Presentation
- 2 Diagnosis
- 3 Genetics
- 4 History
- 5 See also
- 6 References
- 7 External links
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Presentation
The skin lesions evolve through characteristic stages:
- blistering (from birth to about four months of age),
- a wart-like rash (for several months),
- swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
- linear hypopigmentation.
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
Diagnosis
The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKG 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.
Genetics
IP is inherited in an X-linked dominant manner.[3][4] 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 counseling, 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.[5]
IP is caused by mutations in a gene called NEMO (NF-kappaB essential modulator).
History
This disorder was first reported by Bruno Bloch, a German dermatologist in 1926 and Marion Sulzberger, an American dermatologist in 1928.[6][7][8]
See also
- List of cutaneous conditions
References
- ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
- ^ M. B. Sulzberger (1927). Über eine bisher nicht beschriebene kongenitale Pigmentanomalie (incontinentia pigmenti).. Berlin: Archiv für Dermatologie und Syphilis. pp. 154.
- ^ Pettigrew R, Kuo HC, Scriven P et al (December 2000). "A pregnancy following PGD for X-linked dominant [correction of X-linked autosomal dominant incontinentia pigmenti (Bloch-Sulzberger syndrome): case report"]. Hum. Reprod. 15 (12): 2650–2. doi:10.1093/humrep/15.12.2650. PMID 11098039. http://humrep.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11098039.
- ^ "Incontinentia pigmenti. DermNet NZ". http://dermnetnz.org/systemic/incontinentia-pigmenti.html.
- ^ Smahi A, Courtois G, Vabres P et al (2000). "Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium". Nature 405 (6785): 466–72. doi:10.1038/35013114. PMID 10839543.
- ^ synd/1762 at Who Named It?
- ^ B. Bloch. Eigentümliche, bisher nicht beschriebene Pigmentaffektion (incontinentia pigmenti). Schweizerische medizinische Wochenschrift, Basel, 1926, 56: 404-405.
- ^ M. B. Sulzberger. Über eine bisher nicht beschriebene kongenitale Pigmentanomalie (incontinentia pigmenti). Archiv für Dermatologie und Syphilis, Berlin, 1927, 154: 19-32.
External links
- Incontinentia Pigmenti
- Incontinentia Pigmenti France french website
- Incontinentia Pigmenti Video
- GeneReview/NIH/UW entry on Incontinentia Pigmenti
- DermAtlas 166
- Discussion/support/information on Incontinentia Pigmenti
- Incontinentia Pigmenti Support Group
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Congenital malformations and deformations of integument / skin disease (Q80–Q82, 757.0–757.3)
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| Genodermatosis |
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Congenital ichthyosis/
erythrokeratodermia
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AD
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Ichthyosis vulgaris
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AR
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Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis · Lamellar ichthyosis (Harlequin type ichthyosis)
Netherton syndrome · Zunich–Kaye syndrome · Sjögren–Larsson syndrome
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XR
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X-linked ichthyosis
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Ungrouped
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Ichthyosis bullosa of Siemens · Ichthyosis follicularis · Ichthyosis prematurity syndrome · Ichthyosis–sclerosing cholangitis syndrome · Nonbullous congenital ichthyosiform erythroderma · Ichthyosis linearis circumflexa · Ichthyosis hystrix
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EB
and related
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EBS (EBS-K, EBS-WC, EBS-DM, EBS-OG, EBS-MD, EBS-MP)
JEB (JEB-H, Mitis, Generalized atrophic, JEB-PA)
DEB (DDEB, RDEB)
related: Costello syndrome · Kindler syndrome · Laryngoonychocutaneous syndrome · Skin fragility syndrome ·
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Ectodermal dysplasia
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Naegeli syndrome/Dermatopathia pigmentosa reticularis · Hay–Wells syndrome · Hypohidrotic ectodermal dysplasia · Focal dermal hypoplasia · Ellis–van Creveld syndrome · Rapp–Hodgkin syndrome/Hay–Wells syndrome
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Elastic/Connective
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Ehlers–Danlos syndrome · Cutis laxa (Gerodermia osteodysplastica) · Popliteal pterygium syndrome · Pseudoxanthoma elasticum · Van Der Woude syndrome
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Hyperkeratosis/
keratinopathy
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PPK
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diffuse: Diffuse epidermolytic palmoplantar keratoderma • Diffuse nonepidermolytic palmoplantar keratoderma • Palmoplantar keratoderma of Sybert • Mal de Meleda •
syndromic (connexin (Bart–Pumphrey syndrome • Clouston's hidrotic ectodermal dysplasia • Vohwinkel syndrome) • Corneodermatoosseous syndrome • plakoglobin (Naxos syndrome) • Scleroatrophic syndrome of Huriez • Olmsted syndrome • Cathepsin C (Papillon–Lefèvre syndrome • Haim–Munk syndrome) • Camisa disease
focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis • Focal palmoplantar and gingival keratosis • Howel–Evans syndrome • Pachyonychia congenita (Pachyonychia congenita type I • Pachyonychia congenita type II) • Striate palmoplantar keratoderma • Tyrosinemia type II)
punctate: Acrokeratoelastoidosis of Costa • Focal acral hyperkeratosis • Keratosis punctata palmaris et plantaris • Keratosis punctata of the palmar creases • Schöpf–Schulz–Passarge syndrome • Porokeratosis plantaris discreta • Spiny keratoderma
ungrouped: Palmoplantar keratoderma and spastic paraplegia • desmoplakin (Carvajal syndrome) • connexin (Erythrokeratodermia variabilis • HID/KID)
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Other
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Meleda disease · Keratosis pilaris · ATP2A2 (Darier's disease) · Dyskeratosis congenita · Lelis syndrome
Dyskeratosis congenita · Keratolytic winter erythema · Keratosis follicularis spinulosa decalvans · Keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome · Keratosis pilaris atrophicans faciei · Keratosis pilaris
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Other
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cadherin (EEM syndrome) · immune system (Hereditary lymphedema, Mastocytosis/Urticaria pigmentosa) · Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
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Developmental
anomalies |
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Midline
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Dermoid cyst · Encephalocele · Nasal glioma · PHACE association · Sinus pericranii
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Nevus
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Capillary hemangioma · Port-wine stain (Nevus flammeus nuchae)
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Other/ungrouped
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Aplasia cutis congenita · Amniotic band syndrome · Branchial cyst · Cavernous venous malformation
Accessory nail of the fifth toe · Bronchogenic cyst · Congenital cartilaginous rest of the neck · Congenital hypertrophy of the lateral fold of the hallux · Congenital lip pit · Congenital malformations of the dermatoglyphs · Congenital preauricular fistula · Congenital smooth muscle hamartoma · Cystic lymphatic malformation · Median raphe cyst · Melanotic neuroectodermal tumor of infancy · Mongolian spot · Nasolacrimal duct cyst · Omphalomesenteric duct cyst · Poland anomaly · Rapidly involuting congenital hemangioma · Rosenthal–Kloepfer syndrome · Skin dimple · Superficial lymphatic malformation · Thyroglossal duct cyst · Verrucous vascular malformation · Birthmark
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noco(i/b/d/q/u/r/p/m/k/v/f)/cong/tumr(n/e/d), sysi/epon
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proc, drug (D2/3/4/5/8/11)
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Phakomatosis (Q85, 759.5–759.6)
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| Neurofibromatosis |
Type I · Type II
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| Angiomatosis |
Sturge–Weber syndrome · Von Hippel–Lindau disease
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| Hamartoma |
Tuberous sclerosis · Hypothalamic hamartoma (Pallister-Hall syndrome) · Multiple hamartoma syndrome (Proteus syndrome, Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Lhermitte-Duclos disease)
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| Other |
Abdallat Davis Farrage syndrome · Ataxia telangiectasia · Incontinentia pigmenti · Peutz–Jeghers syndrome
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Sex linkage: X-linked disorders
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X-linked recessive
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| Immune |
Chronic granulomatous disease (CYBB) · Wiskott–Aldrich syndrome · X-linked severe combined immunodeficiency · X-linked agammaglobulinemia · Hyper-IgM syndrome type 1 · IPEX · X-linked lymphoproliferative disease · Properdin deficiency
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| Hematologic |
Haemophilia A · Haemophilia B · X-linked sideroblastic anemia
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| Endocrine |
Androgen insensitivity syndrome/Kennedy disease · KAL1 Kallmann syndrome · X-linked adrenal hypoplasia congenita
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| Metabolic |
amino acid: Ornithine transcarbamylase deficiency · Oculocerebrorenal syndrome
dyslipidemia: Adrenoleukodystrophy
carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency · Pyruvate dehydrogenase deficiency · Danon disease/glycogen storage disease Type IIb
lipid storage disorder: Fabry's disease
mucopolysaccharidosis: Hunter syndrome
purine-pyrimidine metabolism: Lesch–Nyhan syndrome
mineral: Menkes disease/Occipital horn syndrome
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| Nervous system |
X-Linked mental retardation: Coffin–Lowry syndrome · MASA syndrome · X-linked alpha thalassemia mental retardation syndrome · Siderius X-linked mental retardation syndrome
eye disorders: Color blindness (red and green, but not blue) · Ocular albinism (1) · Norrie disease · Choroideremia
other: Charcot–Marie–Tooth disease (CMTX2-3) · Pelizaeus–Merzbacher disease · SMAX2
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| Skin and related tissue |
Dyskeratosis congenita · Hypohidrotic ectodermal dysplasia (EDA) ·
X-linked ichthyosis · X-linked endothelial corneal dystrophy
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| Neuromuscular |
Becker's muscular dystrophy/Duchenne · Centronuclear myopathy (MTM1) · Conradi–Hünermann syndrome · Emery–Dreifuss muscular dystrophy 1
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| Urologic |
Alport syndrome · Dent's disease · X-linked nephrogenic diabetes insipidus
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| Bone/tooth |
AMELX Amelogenesis imperfecta
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| No primary system |
Barth syndrome · McLeod syndrome · Smith-Fineman-Myers syndrome · Simpson–Golabi–Behmel syndrome · Mohr–Tranebjærg syndrome · Nasodigitoacoustic syndrome
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X-linked dominant
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X-linked hypophosphatemia · Focal dermal hypoplasia · Fragile X syndrome · Aicardi syndrome · Incontinentia pigmenti · Rett syndrome · CHILD syndrome · Lujan–Fryns syndrome · Orofaciodigital syndrome 1
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Deficiencies of intracellular signaling peptides and proteins
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| GTP-binding protein regulators |
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GTPase-activating protein
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Neurofibromatosis type I · Watson syndrome · Tuberous sclerosis
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Guanine nucleotide exchange factor
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Marinesco–Sjögren syndrome · Aarskog–Scott syndrome · Juvenile primary lateral sclerosis · X-Linked mental retardation 1
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| G protein |
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Heterotrimeic
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cAMP/GNAS1: Pseudopseudohypoparathyroidism · Progressive osseous heteroplasia · Pseudohypoparathyroidism · Albright's hereditary osteodystrophy · McCune–Albright syndrome
CGL 2
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Monomeric
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RAS: HRAS (Costello syndrome) · KRAS (Noonan syndrome 3, KRAS Cardiofaciocutaneous syndrome)
RAB: RAB7 (Charcot–Marie–Tooth disease) · RAB23 (Carpenter syndrome) · RAB27 (Griscelli syndrome type 2)
RHO: RAC2 (Neutrophil immunodeficiency syndrome)
ARF: SAR1B (Chylomicron retention disease) ARL13B (Joubert syndrome 8) · ARL6 (Bardet–Biedl syndrome 3)
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| MAP kinase |
Cardiofaciocutaneous syndrome
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| Other kinase/phosphatase |
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Tyrosine kinase
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BTK (X-linked agammaglobulinemia) · ZAP70 (ZAP70 deficiency)
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Serine/threonine kinase
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RPS6KA3 (Coffin-Lowry syndrome) · CHEK2 (Li-Fraumeni syndrome 2) · IKBKG (Incontinentia pigmenti) · STK11 (Peutz–Jeghers syndrome) · DMPK (Myotonic dystrophy 1) · ATR (Seckel syndrome 1) · GRK1 (Oguchi disease 2) · WNK4/WNK1 (Pseudohypoaldosteronism 2)
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Tyrosine phosphatase
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PTEN (Bannayan–Riley–Ruvalcaba syndrome, Lhermitte–Duclos disease, Cowden syndrome, Proteus-like syndrome) · MTM1 (X-linked myotubular myopathy) · PTPN11 (Noonan syndrome 1, LEOPARD syndrome, Metachondromatosis)
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| Signal transducing adaptor proteins |
EDARADD (EDARADD Hypohidrotic ectodermal dysplasia) · SH3BP2 (Cherubism) · LDB3 (Zaspopathy)
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| Other |
NF2 (Neurofibromatosis type II) · NOTCH3 (CADASIL) · PRKAR1A (Carney complex) · PRKAG2 (Wolff–Parkinson–White syndrome) · PRKCSH (PRKCSH Polycystic liver disease) · XIAP (XIAP2)
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see also intracellular signaling peptides and proteins
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk
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Pigmentation disorders/Dyschromia (L80–L81, 709.0)
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Hypo-/
leucism |
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Loss of melanocytes
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vitiligo: Quadrichrome vitiligo · Vitiligo ponctué · syndromic (Alezzandrini syndrome · Vogt–Koyanagi–Harada syndrome)
melanocyte development: Piebaldism · Waardenburg syndrome · Tietz syndrome
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Loss of melanin/
amelanism
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albinism: Oculocutaneous albinism · Ocular albinism
melanosome transfer: Hermansky–Pudlak syndrome · Chédiak–Higashi syndrome · Griscelli syndrome (Elejalde syndrome · Griscelli syndrome type 2 · Griscelli syndrome type 3)
other: Cross syndrome · ABCD syndrome · Albinism–deafness syndrome · Idiopathic guttate hypomelanosis · Phylloid hypomelanosis · Progressive macular hypomelanosis
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Leukoderma w/o
hypomelanosis
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Vasospastic macule · Woronoff's ring · Nevus anemicus
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Ungrouped
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ungrouped: Nevus depigmentosus · Postinflammatory hypopigmentation · Pityriasis alba · Vagabond's leukomelanoderma · Yemenite deaf-blind hypopigmentation syndrome · Wende–Bauckus syndrome
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| Hyper- |
Melanin/
Melanosis/
Melanism |
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Reticulated
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Dermatopathia pigmentosa reticularis · Pigmentatio reticularis faciei et colli · Reticulate acropigmentation of Kitamura · Reticular pigmented anomaly of the flexures · Naegeli–Franceschetti–Jadassohn syndrome · Dyskeratosis congenita · X-linked reticulate pigmentary disorder · Galli–Galli disease · Revesz syndrome
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Diffuse/
circumscribed
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Lentigo/Lentiginosis: Lentigo simplex · Liver spot · Centrofacial lentiginosis · Generalized lentiginosis · Inherited patterned lentiginosis in black persons · Ink spot lentigo · Lentigo maligna · Mucosal lentigines · Partial unilateral lentiginosis · PUVA lentigines
Melasma · Erythema dyschromicum perstans · Lichen planus pigmentosus · Café au lait spot · Poikiloderma (Poikiloderma of Civatte · Poikiloderma vasculare atrophicans) · Riehl melanosis
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Linear
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Incontinentia pigmenti · Scratch dermatitis · Shiitake mushroom dermatitis
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Other/ungrouped
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Acanthosis nigricans (Acral acanthotic anomaly) · Freckle · Familial progressive hyperpigmentation · Pallister–Killian syndrome · Periorbital hyperpigmentation · Photoleukomelanodermatitis of Kobori · Postinflammatory hyperpigmentation · Transient neonatal pustular melanosis
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Other
pigments
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iron: Hemochromatosis · Iron metallic discoloration · Pigmented purpuric dermatosis (Schamberg disease, Majocchi's disease, Gougerot–Blum syndrome, Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis, Lichen aureus, Angioma serpiginosum) · Hemosiderin hyperpigmentation
other metals: Argyria · Chrysiasis · Arsenic poisoning · Lead poisoning · Titanium metallic discoloration
other: Carotenosis · Tattoo · Tar melanosis
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| Dyschromatoses |
Dyschromatosis symmetrica hereditaria · Dyschromatosis universalis hereditaria
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noco(i/b/d/q/u/r/p/m/k/v/f)/cong/tumr(n/e/d), sysi/epon
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proc, drug (D2/3/4/5/8/11)
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