Incontinentia pigmenti

General Information (adopted from Orphanet):

Synonyms, Signs: IP2, FORMERLY
INCONTINENTIA PIGMENTI, TYPE II, FORMERLY
INCONTINENTIA PIGMENTI, FAMILIAL MALE-LETHAL TYPE
IP
Bloch-Siemens syndrome
bloch-sulzberger syndrome
Number of Symptoms 109
OrphanetNr: 464
OMIM Id: 308300
ICD-10: Q82.3
UMLs:
MeSH: D007184
MedDRA:
Snomed: 367520004

Prevalence, inheritance and age of onset:

Prevalence: 0.7 of 100 000 [Orphanet]
Inheritance: X-linked dominant
[Orphanet]
Age of onset: Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Congenital vitreoretinal dysplasia
 -Rare eye disease
 -Rare genetic disease
Dentocutaneous disease with cataract
 -Rare eye disease
 -Rare genetic disease
Ectodermal dysplasia syndrome
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare skin disease
Neurocutaneous syndrome with epilepsy
 -Rare genetic disease
 -Rare neurologic disease
Pigmentation disorder with eye involvement, excluding albinism
 -Rare eye disease
 -Rare genetic disease
Precancerous lesion of palpebral epidermis
 -Rare eye disease
 -Rare genetic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000202) Oral cleft Frequent [Orphanet] 120 / 7739
2
(HPO:0000684) Delayed eruption of teeth Frequent [Orphanet] 117 / 7739
3
(HPO:0001357) Plagiocephaly Frequent [Orphanet] 106 / 7739
4
(HPO:0009804) Reduced number of teeth Very frequent [Orphanet] 137 / 7739
5
(HPO:0000668) Hypodontia 81 / 7739
6
(HPO:0000252) Microcephaly 832 / 7739
7
(HPO:0000568) Microphthalmia 183 / 7739
8
(HPO:0000682) Abnormality of dental enamel Occasional [Orphanet] 102 / 7739
9
(HPO:0006482) Abnormality of dental morphology Frequent [Orphanet] 81 / 7739
10
(HPO:0007850) Retinal vascular proliferation 1 / 7739
11
(HPO:0100533) Inflammatory abnormality of the eye Occasional [Orphanet] 70 / 7739
12
(HPO:0000518) Cataract Occasional [Orphanet] 454 / 7739
13
(HPO:0000592) Blue sclerae Occasional [Orphanet] 85 / 7739
14
(HPO:0000486) Strabismus Frequent [Orphanet] 576 / 7739
15
(HPO:0000648) Optic atrophy 238 / 7739
16
(HPO:0000541) Retinal detachment Occasional [Orphanet] 87 / 7739
17
(HPO:0000479) Abnormality of the retina Occasional [Orphanet] 74 / 7739
18
(HPO:0000554) Uveitis 10 / 7739
19
(HPO:0008046) Abnormality of the retinal vasculature Occasional [Orphanet] 41 / 7739
20
(HPO:0000481) Abnormality of the cornea Frequent [Orphanet] 124 / 7739
21
(HPO:0000572) Visual loss Frequent [Orphanet] 272 / 7739
22
(HPO:0000573) Retinal hemorrhage 13 / 7739
23
(HPO:0008056) Aplasia/Hypoplasia affecting the eye Occasional [Orphanet] 142 / 7739
24
(HPO:0000491) Keratitis 21 / 7739
25
(HPO:0000598) Abnormality of the ear Frequent [Orphanet] 98 / 7739
26
(HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
27
(HPO:0001249) Intellectual disability 1089 / 7739
28
(HPO:0001257) Spasticity 251 / 7739
29
(HPO:0004374) Hemiplegia/hemiparesis Occasional [Orphanet] 158 / 7739
30
(HPO:0002383) Encephalitis Occasional [Orphanet] 41 / 7739
31
(HPO:0001276) Hypertonia Occasional [Orphanet] 317 / 7739
32
(HPO:0001288) Gait disturbance Frequent [Orphanet] 318 / 7739
33
(HPO:0000752) Hyperactivity Frequent [Orphanet] 140 / 7739
34
(HPO:0011442) Abnormality of central motor function Occasional [Orphanet] 76 / 7739
35
(HPO:0002558) Supernumerary nipple Frequent [Orphanet] 40 / 7739
36
(HPO:0002557) Hypoplastic nipples 33 / 7739
37
(HPO:0100783) Breast aplasia 19 / 7739
38
(HPO:0003187) Breast hypoplasia 17 / 7739
39
(HPO:0001155) Abnormality of the hand Frequent [Orphanet] 54 / 7739
40
(HPO:0004050) Absent hand Occasional [Orphanet] 9 / 7739
41
(HPO:0006101) Finger syndactyly Occasional [Orphanet] 198 / 7739
42
(HPO:0009466) Radial deviation of finger Frequent [Orphanet] 101 / 7739
43
(HPO:0002797) Osteolysis Frequent [Orphanet] 68 / 7739
44
(HPO:0003298) Spina bifida occulta Occasional [Orphanet] 67 / 7739
45
(HPO:0100490) Camptodactyly of finger Frequent [Orphanet] 212 / 7739
46
(HPO:0002751) Kyphoscoliosis 131 / 7739
47
(HPO:0000772) Abnormality of the ribs Frequent [Orphanet] 146 / 7739
48
(HPO:0005815) Supernumerary ribs 9 / 7739
49
(HPO:0002650) Scoliosis Frequent [Orphanet] 705 / 7739
50
(HPO:0002937) Hemivertebrae 41 / 7739
51
(HPO:0001537) Umbilical hernia Occasional [Orphanet] 206 / 7739
52
(HPO:0100555) Asymmetric growth Frequent [Orphanet] 25 / 7739
53
(HPO:0004322) Short stature Frequent [Orphanet] 1232 / 7739
54
(HPO:0004529) Atrophic, patchy alopecia 1 / 7739
55
(HPO:0001053) Hypopigmented skin patches Very frequent [Orphanet] 80 / 7739
56
(HPO:0100585) Telangiectasia of the skin Very frequent [Orphanet] 66 / 7739
57
(HPO:0200042) Skin ulcer Frequent [Orphanet] 138 / 7739
58
(HPO:0200037) Skin vesicle Very frequent [Orphanet] 102 / 7739
59
(HPO:0001804) Hypoplastic fingernail Very frequent [Orphanet] 62 / 7739
60
(HPO:0002208) Coarse hair 58 / 7739
61
(HPO:0001596) Alopecia Frequent [Orphanet] 162 / 7739
62
(HPO:0010783) Erythema Very frequent [Orphanet] 138 / 7739
63
(HPO:0008388) Abnormality of the toenails Occasional [Orphanet] 28 / 7739
64
(HPO:0002213) Fine hair 77 / 7739
65
(HPO:0001595) Abnormality of the hair Very frequent [Orphanet] 89 / 7739
66
(HPO:0000988) Skin rash Very frequent [Orphanet] 98 / 7739
67
(HPO:0007400) Irregular hyperpigmentation Very frequent [Orphanet] 72 / 7739
68
(HPO:0008404) Nail dystrophy 89 / 7739
69
(HPO:0001231) Abnormality of the fingernails Very frequent [Orphanet] 116 / 7739
70
(HPO:0001803) Nail pits 17 / 7739
71
(HPO:0000962) Hyperkeratosis Frequent [Orphanet] 216 / 7739
72
(HPO:0001805) Thick nail Occasional [Orphanet] 96 / 7739
73
(HPO:0001807) Ridged nail 20 / 7739
74
(HPO:0001597) Abnormality of the nail Very frequent [Orphanet] 115 / 7739
75
(HPO:0008070) Sparse hair 94 / 7739
76
(HPO:0001000) Abnormality of skin pigmentation Very frequent [Orphanet] 105 / 7739
77
(HPO:0002164) Nail dysplasia 82 / 7739
78
(HPO:0002140) Ischemic stroke Occasional [Orphanet] 70 / 7739
79
(HPO:0001635) Congestive heart failure Occasional [Orphanet] 232 / 7739
80
(HPO:0002092) Pulmonary hypertension Occasional [Orphanet] 109 / 7739
81
(HPO:0001879) Abnormality of eosinophils Frequent [Orphanet] 20 / 7739
82
(HPO:0001880) Eosinophilia 35 / 7739
83
(HPO:0010978) Abnormality of immune system physiology Frequent [Orphanet] 148 / 7739
84
(HPO:0001252) Muscular hypotonia Occasional [Orphanet] 990 / 7739
85
(HPO:0100699) Scarring 9 / 7739
86
(OMIM) Fades in adolescence 1 / 7739
87
(OMIM) Leukocytosis with eosinophilia during stage 1 1 / 7739
88
(HPO:0002120) Cerebral cortical atrophy Occasional [Orphanet] 187 / 7739
89
(HPO:0012740) Papilloma Very frequent [Orphanet] 17 / 7739
90
(OMIM) Affects distal limb and scalp 1 / 7739
91
(OMIM) STAGE 1 - skin erythema, vesicles, pustules 1 / 7739
92
(OMIM) Subungual keratotic tumors 1 / 7739
93
(OMIM) STAGE 3 - Skin hyperpigmentation 1 / 7739
94
(HPO:0001423) X-linked dominant inheritance 69 / 7739
95
(MedDRA:10071391) Retinal fibrosis 1 / 7739
96
(OMIM) STAGE 2 - Skin papules, verrucous lesions, hyperkeratosis 1 / 7739
97
(OMIM) Accessory cusps 1 / 7739
98
(OMIM) Onset birth-newborn period 1 / 7739
99
(OMIM) Conical forms 1 / 7739
100
(OMIM) Occurs in linear distribution 1 / 7739
101
(OMIM) Wiry, coarse hair (childhood) 1 / 7739
102
(OMIM) Affects limbs and trunk 1 / 7739
103
(OMIM) Primarily affects trunk 1 / 7739
104
(OMIM) Follows Blaschko's lines 1 / 7739
105
(OMIM) Most evident on lower legs 1 / 7739
106
(HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
107
(OMIM) Retinal ischemia 1 / 7739
108
(OMIM) STAGE 4 - skin pallor, atrophy, and scarring 1 / 7739
109
(OMIM) Streaks and whorls 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Familial incontinentia pigmenti (IP) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males (The International Incontinentia Pigmenti Consortium, 2000). In affected females it causes highly variable abnormalities of the skin, ...
Clinical Description OMIM Incontinentia pigmenti is a disturbance of skin pigmentation sometimes associated with a variety of malformations of the eye, teeth, skeleton, heart, etc. The pigmentary disturbance, an autochthonous tattooing, is evident at or soon after birth and may be ...
Molecular genetics OMIM For more complete discussion of the molecular genetics of this disorder, see the entry for the NEMO gene (300248).

The International Incontinentia Pigmenti Consortium (2000) demonstrated that mutations in NEMO cause incontinentia pigmenti type II. The ...

Diagnosis GeneReviews No strict diagnostic criteria for incontinentia pigmenti (IP) exist. Establishing the diagnosis relies on detection of the characteristic clinical findings of the skin, teeth, hair, and nails. ...
Clinical Description GeneReviews Incontinentia pigmenti (IP) is a disorder of the skin, eye, and central nervous system (CNS) that occurs primarily in females and on occasion in males. Affected females have an erythematous, vesicular rash that appears at birth or soon thereafter. The rash evolves over time, becoming verrucous and pigmented, and then atrophic. Adults have areas of linear hypopigmentation. Other manifestations include alopecia, hypodontia/misshapen teeth, leukocytosis with eosinophilia, vascular abnormalities of the retina, and other eye findings. Occasionally, skeletal anomalies, seizures, and intellectual disability are observed....
Genotype-Phenotype Correlations GeneReviews Small IKBKG gene mutations, mainly in exon 10 (including missense, single base insertion/deletion causing frameshift, and nonsense mutations), are associated with a milder IP phenotype in females and a lower risk of miscarriage of male fetuses. Indeed, most of these variants allow survival of males with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) and HED-ID with osteopetrosis and lymphedema (OL-HED-ID) (see Genetically Related Disorders). These mutations result in impaired but not absent NF-kappaB signaling [Fusco et al 2008]....
Differential Diagnosis GeneReviews A diagnosis other than incontinentia pigmenti (IP) should be considered when an individual has skeletal involvement (other than secondary to neurologic deficit), gross neurologic deficit, severe alopecia, atypical hyperpigmentation, or gross hypopigmentation. Body segment asymmetry is not usually associated with IP; however, one individual with IP and transverse terminal upper acromelia has been reported [Hayes et al 2005]....
Management GeneReviews To establish the extent of disease in an individual diagnosed with incontinentia pigmenti (IP), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....