FaCD Online Syndrome Fact Sheet

Last updated: 27 Feb 2008

Name: Incontinentia Pigmenti type 2

Synonym: IP2, Bloch-Sulzberger syndrome

Mode of Inheritance: XLD

OMIM number: 308300  

Genes

NEMO/IKBKG, mapped to Xq28

Tumor features

subungual keratoacanthoma

Tumor features (possible)

keratoacanthoma
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
retinoblastoma
rhabdoid tumor of the kidney
subungual squamous cell cancer
Wilms' tumor (nephroblastoma)

Non-tumor features

cataract
dental abnormalities
developmental delay/mental deficiency/mental retardation
erythematous / vesicular/ verrucous skin eruptions
gross motor delay
hypopigmentation of the skin
seizures
spastic paralysis
strabismus
visual loss
whorled pigmentation of the skin

Comment

This disorder (IP2) is characterized by a skin disorder present at or after birth, developing in 3 phases: first an erythematous, vesicular, rash develops, followed by verrucous changes and after that swirling patterns of pigmentation. These lesions may finally show atrophy and depigmentation. Other features of the disease are anomalies of the nervous system, skeleton, teeth and eyes. Mental retardation is observed in the minority of patients.[1].

A few IP patients (one of them male, with 3 primary neoplasms) with childhood cancer have been reported: AML[2;3], rhabdoid tumor of the kidney[4], Wilms tumor[5] and retinoblastoma[6](including a case with a X;13 translocation[7]. Subungual keratoacanthomas are rare rapidly growing benign tumors, which have been found in association with IP[8]. Nora et al.[9] reported an IP patient with recurrent subungual squamous cell cancer. Keratoacanthoma developing in a hypomelanotic patch has also been reported[12]. [Roberts et al.[4] suggested that the chromosomal instability observed in IP families[10] may increase the risk for (childhood) malignancies as it does in other chromosomal instability disorders. Whether or not the occurrence of childhood malignancy in IP patients is coincidental remains to be seen.

The familial type of IP, IP2, is X-linked dominant (lethal in males), mapped to Xq28. The very rare cases of males with IP might be explained by assuming mosaicism for the genetic defect. Isolated cases may be due to a spontaneous structural defect in the X-chromosome at Xp11.21 (most frequently by an X-Autosome translocation). Happle[11] concludes that a sporadic (i.e. non-hereditary) Incontinentia Pigmenti type does not exist. Rather, these sporadic cases have Hypomelanosis of Ito (IP type 1).

References

[1] Carney RG. Incontinentia Pigmenti. Arch Dermatol 1976; 112:535-542.
[2] Rivera R, Cangir A, Strong L. Incontinentia pigmenti (Bloch-Sulzberger syndrome) associated with acute granulocytic leukemia. South Med J 1975; 68(11):1391-1394.
[3] Schmidt H, Hvidberg-Hansen J, Christensen HE. Incontinentia pigmenti with associated lesions in two generations. Clinical, light microscopic, and electronmicroscopic examinations. Acta Derm Venereol 1972; 52(4):281-287.
[4] Roberts WM, Jenkins JJ, Moorhead EL2, Douglass EC. Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer 1988; 62(11):2370-2372.
[5] Shashikumar VL, Somers LA, Pilling GP, Cresson SL. Wilm's tumor in the horseshoe kidney. J Pediatr Surg 1974; 9(2):185-189.
[6] Blake J, Mullaney J. Retinoblastoma in Bloch-Sulzberger syndrome. Ophthalmologica 1976; 172:457-465.
[7] Kajii T, Tsukahara M, Fukushima Y, Hata A, Matsuo K, Kuroki Y. Translocation (X;13)(p11.21;q12.3) in a girl with incontinentia pigmenti and bilateral retinoblastoma. Ann Genet 1985; 28(4):219-223.
[8] Shatkin BT, Hunter JG, Song IC. Familial subungual keratoacanthoma in association with ectodermal dysplasia. Plast Reconstr Surg 1993; 92(3):528-531.
[9] Shannon N, Giblin CA, Quarrell OWJ, Page RE. Incontinentia pigmenti presenting with recurrent subungal squamous cell carcinoma. J Med Genet 1998; 35(suppl 1):S59.
[10] Cantu JM, del Castillo V, Jimenez M, Ruiz-Barquin E. Chromosomal instability in incontinentia pigmenti. Ann Genet 1973; 16(2):117-119.
[11] Happle R. Incontinentia pigmenta versus hypomelanosis of ito: the whys and wherefores of a confusing issue. Am J Med Genet 1998; 79:64-65.
[12] Sakai H, Minami M, Satoh E, Matsuo S, Iizuka H. Keratoacanthoma developing on a pigmented patch in incontinentia pigmenti. Dermatology (Basel, Switzerland) 2000; 200(3):258-61.