|Year : 2015 | Volume
| Issue : 1 | Page : 74-77
Bloch Sulzberger syndrome (Incontinentia pigmenti): A rare case report with dental defects
Yaga Uday Shankar, Nikhat Fatima, Menji Ashwini Kumar, Kesary Sathya Prakash
Department of Oral Medicine and Radiology, MN Raju Dental College and Hospital, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||9-Jan-2015|
Dr. Nikhat Fatima
Department of Oral Medicine and Radiology, MNR Dental College and Hospital, Narsapur Road, Sangareddy, Hyderabad - 500 072, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Incontinentia Pigmenti (IP) is a multisystem genodermatosis characterized by cutaneous, neurologic, ophthalmologic, and dental abnormalities. This article reports the clinical features and management of a 4-year-old girl diagnosed with IP.
Keywords: Hypodontia, incontinentia, pigmenti, whorly pigmentation
|How to cite this article:|
Shankar YU, Fatima N, Kumar MA, Prakash KS. Bloch Sulzberger syndrome (Incontinentia pigmenti): A rare case report with dental defects. J Indian Soc Pedod Prev Dent 2015;33:74-7
|How to cite this URL:|
Shankar YU, Fatima N, Kumar MA, Prakash KS. Bloch Sulzberger syndrome (Incontinentia pigmenti): A rare case report with dental defects. J Indian Soc Pedod Prev Dent [serial online] 2015 [cited 2020 May 27];33:74-7. Available from: http://www.jisppd.com/text.asp?2015/33/1/74/149014
| Introduction|| |
Incontinentia Pigmenti (IP) also known as Bloch Sulzberger disease is a genodermatosis manifested as characteristic dermatological polymorphism with three different stages: Vesiculobullous, verrucous and swirled hyperpigmentation.  IP is an X-linked dominant disorder predominantly affecting females and lethal to males. 
IP is a single-gene disorder caused by mutations in the NEMO/IKK-g gene. The function of NEMO, a 23 kb gene consisting of 10 exons, is to permit cells to respond to external signals such as growth factors.  This gene encodes a protein that regulates the function of various chemokines, cytokines and adhesion molecules, and is essential for protection against tumor necrosis factor induced apoptosis. ,,
The inheritance of a mutant copy of this X-linked gene is generally lethal in antenatal males. Although there are many case reports of men with IP submitted to mutation analysis, none of these patients has been shown to carry the common NEMO deletion. Several studies have demonstrated the presence of hypomorphic NEMO alleles, a finding suggesting that less severe NEMO mutations permit the survival of affected men. , There are also several reports of men with IP who present the 47, XXY karyotype (Klinefelter syndrome). ,
This genodermatosis affects mostly females and may involve the skin, hair, nails, eyes, and central nervous system. Diagnosis usually is made from the clinical presentation and occasionally skin biopsy. IP is one of the lesser known ectodermal dysplasias with less than thousand cases reported in the world literature. 
Characteristic changes in the dentition of some patients also have been observed. Dental abnormalities include hypodontia, pegged incisors and canines, and delayed eruption.  Here is a case of a 4-year-old female with IP associated with hypodontia.
| Case Report|| |
A 4-year-old child reported to the department of Oral Medicine and Radiology with a complaint of missing teeth. History revealed that the child was delivered with a caesarian section post term. Childs parents give no history of consanguineous marriage. At the time of birth of the child, pustules and erosions were present all over the body, more on upper limb and chest and was diagnosed as Birth Asphyxia at the Government Medical Hospital. At the age of 2 months, she visited a private medical hospital due to the persistence of the vesicles, where she was diagnosed as Epidermolysis Bullosa Simplex Herpetiformis. By the end of 4 months, her right eye vision got impaired with partial impairment of left eye. She underwent left eye surgery for vision enhancement.
Presently at the age of 4 years, patient came to our department with the complaint of missing teeth.
Her general physical examination revealed that the child is conscious, coherent, cooperative, with normal gait and moderate built.
Skin showed whorly pigmentation at the peri-oral area, infra-orbital region, chest region, axilla (upper trunk) [Figure 1] and [Figure 2]. She also presented with strabismus, frontal bossing, and vertex alopecia.
|Figure 1: Profile photograph showing strabismus, frontal bossing and whorly pigmentation at the perioral region|
Click here to view
Intra-oral examination revealed hypodontia. Teeth present were: Deciduous central and lateral incisor of upper right quadrant (51, 52), deciduous central and lateral incisor of upper left quadrant (61, 62), deciduous central incisors of lower right and left quadrants (71, 81). Peg shaped teeth were seen in relation to deciduous lateral incisors of upper right and left quadrants (52, 62) [Figure 3] and [Figure 4].
|Figure 3: Maxillary arch with teeth present-51,52,61,62. Peg shaped teeth irt. 52,62|
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An Orthopantomograph was taken which revealed hypodontia and an erupting deciduous first molar in lower left quadrant (74) [Figure 5].
With the positive findings of hypodontia, peg shaped teeth, whorly pigmented areas on skin, strabismus, vision impairment, frontal bossing and vertex alopecia the case was provisionally diagnosed as IP.
Skin biopsy was performed. The histopathologic section showed melanophages in the superficial dermis due to melanin incontinence which confirmed the diagnosis of IP.
| Discussion|| |
First reported by Garrod in 1906,  the name IP is derived from the common histologic finding of incontinent melanin in the superficial dermis. , The syndrome is not known to be more common to any racial group. As it is X-linked dominant, the vast majority of cases are seen in female individuals. The recently discovered genetic mutation in IP lies in the NEMO/IKK-gene that encodes a protein important in signaling pathways of apoptosis and inflammatory responses. 
IKBKG (Inhibitor of Kappa light polypeptide gene enhancer in B-cells, Kinase Gamma, previously NEMO) is the only gene known to be associated with IP.  Mutations of the IKBKG gene are responsible for IP.  The IKBKG gene is composed of 10 exons. Located at Xq28, IKBKG has a unique genomic organization, as it is part of a segmental duplication or low-copy repeat 1 and 2 (LCR1 and LCR2) containing the gene and its pseudogene copy (IKBKGP1). The two LCRs in the IKBKG locus are able to recombine producing a pathological recurrent IKBKG exon 4-10 deletion. 
Within cells, the IKBKG protein interacts with two enzymes, IKK-alpha and IKK-beta, to activate NF-κB (Nuclear Factor-kappa-B). The activated factor then moves into the nucleus and binds to DNA. NF-κB regulates the activity of multiple genes, including genes that control the body's immune responses and inflammatory reactions. It also protects the cell from certain signals that would otherwise undergo apoptosis.  Its misregulation is involved in many diseases.  However, failure to identify IKBKG mutations does not rule out the diagnosis of IP.  The phenotypic expression of IKBKG mutation is highly variable, even among related patients with the same mutation.  Because females with IP have skewed X-chromosome inactivation in which the X-chromosome with the mutant IKBKG allele is preferentially inactivated  it was thought that this variability was likely to be result of skewed X-chromosome inactivation.  It was also suggested that the phenotype of IP might be due to the pleiotropic role of the NF-κB.
Etiology of IP in this case is probably a sporadic mutation. No evidence of enamel defects or malformations of teeth were noticed among parents. No skin abnormalities were present, nor was there a history of any abnormalities of ectodermal structures. Finally, no family members were reported to have IP or other dermatological diseases.
Diagnosis of the disease is aided by family history and history of miscarriages of male gender. Male patients with IP have rarely been reported, mostly in association with Kleinfelter syndrome, in which the XXY genotype permits viability. 
IP is typically diagnosed by its cutaneous signs, which classically evolve through four stages.
- The vesicobullous first stage (stage 1) typically occurs from birth to the first 2 weeks of life and constitutes erythematous vesicles or bullae arranged linearly on the extremities, trunk, and scalp. 
- The verrucous second stage (stage 2) manifests after several weeks of birth and could last for weeks. Stage 2 is characterized by the presence of hyperkeratotic, verrucous lesions on an erythematous base that usually affects the distal extremities. ,, They may evolve from stage 1 or occur on previously uninvolved skin.
- The hyperpigmented (stage 3) generally occurs between the ages of 3 and 6 months and could last from months to years.  Features include asymmetrically distributed hyperpigmented streaks or whorls that occur along the Lines of Blaschko More Details, which refer to the common pattern of skin findings in specific skin disorders such as linear epidermal nevi, IP, hypomelanosis of Ito, and focal dermal hypoplasia. 
- The hypopigmented (stage 4) could become evident any time between the late infant and adolescent years and usually lasts a lifetime.  Atrophic streaks or whorls of hypopigmentation, which are mostly apparent on the flexor surface of the lower extremities, are characteristic of this stage.4 Eccrine glands and hair follicles are not present in this stage, which can be subtle. 
The most commonly reported dental anomalies in IP patients are hypodontia and malformed or pegged teeth (usually anteriors). Both deciduous and permanent dentition will be affected. In the present case, hypodontia of deciduous teeth were observed.
Ocular defects are found in avout 40% of cases, many patients being blind. Asymmetric involvement is most common, although bilateral ocular lesions may occur as well.  The defects include strabismus, cataract, conjunctival pigmentosa uveitis, optic atrophy, retinal vascular abnormalities, blue sclera, microopthalmia also occurs. ,,, The child in the present case was observed to have strabismus with loss of vision.
Retinal lesions may affect the peripheral retina and macula and generally appear to be result of vaso-occlusive events and ischemia with subsequent compensatory vasoproliferation. They become evident between neonatal period and one year of age. 
CNS disorders occur in about 25% of cases. They include seizures, mental retardation, spacticity, cerebral atrophy, hemiparesis and encephalopathy.  No CNS abnormalities were present in the present case.
The clinical manifestations including the dental and dermatological findings closely resemble those of ectodermal dysplasia but the skin lesions in IP are preceeded by inflammatory vesiculations. 
The differential diagnosis of the vesiculobullous first stage of IP includes neonatal HSV, herpes zoster, congential candidiasis, congenital syphilis, bullous impetigo, epidermolysis bullosa simplex (Dowling- Meara type), Letterer-Siwe disease, blistering drug eruption, epidermolytic hyperkeratosis (also known as bullous congenital ichthyosiform erythroderma), allergic contact dermatitis, and neonatal dermatitis herpetiformis. ,,,, The histologic differential diagnosis of allergic contact dermatitis, arthropod assault, drug eruption, nummular dermatitis, and occasionally, bacterial or fungal infection. 
| Conclusion|| |
Since IP shows varying degree of involvement of different systems as presented in the present case, a multidisciplinary approach is therefore warranted for the rehabilitation of such patients. The patients suffering from IP should be continuously reviewed by the ophthalmologist, dental surgeon and neurologist. The periodic dental follow up should emphasize the assessment of caries risk and implementation of preventive protocols.
| References|| |
Carney RG. Incontinentia pigmenti. A world statistical analysis. Arch Dermatol 1976;112:535-42.
Prendiville JS, Gorski JL, Stein CK, Esterly NB. Incontinentia pigmenti in a male infant with kleinfelter syndrome. J Am Acad Dermatol 1989;20:937-40.
Arenas-Sordo Mde L, Vallejo-Vega B, Hernandez-Zamora E, Galvez-Rosas A, Montoya-Perez LA. Incontinentia pigmenti (IP2): Familiar case report with affected men. Literature review. Med Oral Patol Oral Cir Bucal 2005;10 Suppl 2:E122-9.
Berlin AL, Paller AS, Chan LS. Incontinentia pigmenti: A review and update on the molecular basis of pathophysiology. J Am Acad Dermatol 2002;47:169-87.
Phan TA, Wargon O, Turner AM. Incontinentia pigmenti case series: Clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives. Clin Exp Dermatol 2005;30:474-80.
Aradhya S, Courtois G, Rajkovic A, Lewis RA, Levy M, Israël A, et al
. Atypical forms of incontinentia pigmenti in male individuals result from mutations of a cytosine tract in exon 10 of NEMO (IKK-gamma). Am J Hum Genet 2001;68:765-71.
Kenwrick S, Woffendin H, Jakins T, Shuttleworth SG, Mayer E, Greenhalgh L, et al
; International IP Consortium. Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome. Am J Hum Genet 2001;69:1210-7.
Cho SY, Lee CK, Drummond BK. Surviving male with incontinentia pigmenti: A case report. Int J Paediatr Dent 2004;14:69-72.
Burgess MC. Incontinentia pigmenti: 6 cases of Bloch-Sulzberger syndrome Br Dent J 1982;152:195-6.
Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet 1993;30:53-9.
Sulzberger MB. Arch Dermatol Syphilol 1938;38:57-69.
Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al
. Genomic rearrangement in NEMO impairs NF-êappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 2000;405:466-72.
Fusco F, Paciolla M, Napolitano F, Pescatore A, D′Addario I, Bal E, et al
. Genomic architecture at the Incontinentia Pigmenti locus favours de novo pathological alleles through different mechanisms. Hum Mol Genet 2012;21:1260-71.
Genetics Home Reference. Genes. IKBKG. [Internet]. National Library of Medicine, Lister Hill National Center for Biomedical Communications. Published: June 25, 2012. Available from: http://ghr.nlm.nih.gov/gene/IKBKG
[Last accessed on 2012 Jul 1].
Courtois G, Gilmore TD. Mutations in the NF-êappaB signaling pathway: Implication for human disease. Oncogene 2006;25:6831-43.
Parrish JE, Scheuerle AE, Lewis RA, Levy ML, Nelson DL. Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2. Hum Mol Genet 1996;5:1777-83.
Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, et al
. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-êappaB activation. Hum Mol Genet 2004;13:1763-73.
Scheuerle AE. Male cases of incontinentia pigmenti: Case report and review. Am J Med Genet 1988;77:201-18.
Cohen BA. Incontinentia pigmenti. Neurol Clin 1987;5:361-77.
Bolognia JL, Orlow SJ, Glick SA. Lines of Blaschko. J Am Acad Dermatol 1994;31:157-90.
Parish LC, Brenner S. Womens Dermatology; From infancy to maturity. 2001. p. 89-92.
Rook/Wilkilson/Ebling. 5 th
ed. Text book of dermatology. 1992. p. 1580-2.
Chan YC, Happle R, Giam YC. Whorled scarring alopecia: A rare phenomenon in incontinentia pigmenti. J Am Acad Dermatol 2003;49:929-31.
Arnold/Odom/James/Andrews. 8 th
ed. Diseases of Skin- Clinical Dermatology. 1990.
Francis JS, Sybert VP. Incontinentia pigmenti. Semin Cutan Med Surg 1997;16:54-60.
Gorski JL, Burright EN. The molecular genetics of incontinentia pigmenti. Semin Dermatol 1993;12:255-65.
Bolongia JL, Jorizzo JL, Rapini RP, et al
. Dermatology. New York: Elsevier Ltd; 2003. p. 458.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]