Journal of Pediatric Dentistry

: 2017  |  Volume : 5  |  Issue : 2  |  Page : 29--35

Incontinentia pigmenti: A case report and literature review

Chaitanya Prakash Puranik, Deborah A Redford-Badwal 
 Department of Pediatric Dentistry, Division of Craniofacial Sciences, University of Connecticut Health Center, Farmington, CT, USA

Correspondence Address:
Dr. Chaitanya Prakash Puranik
Department of Pediatric Dentistry, Division of Craniofacial Sciences, School of Dental Medicine, 263 Farmington Ave., Farmington, CT


Incontinentia pigmenti (IP; OMIM#308300) is a rare multisystem disorder with an incidence of 0.7:100,000 live births. IP is rare and predominantly seen in females. Mutations in IKBKG gene (Xq28, GenBank: NM_003639.3, OMIM#300248) were reported as underlying cause of IP. IKBKG encode NFkB protein, which controls the expression of other genes involved in cell proliferation, immunity, and inflammation. Oro-dental abnormalities have been documented in 50%–75% IP cases. We present a case report of a 16-year-old female with probable clinical IP, Arnold–Chiari malformation, hydrocephalus, delayed psychological development, and seizures. The IP hallmark feature: hyperpigmentation of the skin along the Blaschko's lines was present only on the left side of the body. Left-sided hemifacial and tongue hypertrophy were present, which have not been reported previously. Consistent with published reports, tooth size and shape discrepancies were present. However, unlike previous reports, discrepancies were prominent on affected versus unaffected side. This paper provides IP literature review, clinical considerations, and insight on management.

How to cite this article:
Puranik CP, Redford-Badwal DA. Incontinentia pigmenti: A case report and literature review.J Pediatr Dent 2017;5:29-35

How to cite this URL:
Puranik CP, Redford-Badwal DA. Incontinentia pigmenti: A case report and literature review. J Pediatr Dent [serial online] 2017 [cited 2020 Feb 19 ];5:29-35
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Incontinentia pigmenti (IP; OMIM#308300) is also known as Bloch–Sulzberger syndrome, Siemens–Bloch syndrome, melanoblastosis cutis linearis, or pigmented dermatosis. IP is an X-linked, genodermatosis, and multisystem disorder. The prevalence of IP is 0.7/100,000 (Orphanet Report Series, 2011) with mutations in the inhibitor of kappa B kinase gamma (IKBKG, Xq28; earlier known as NEMO). IKBKG gene encodes NFkB protein, which controls the expression of other genes involved in cell proliferation, immunity, and inflammation. IP predominantly affects females and is thought to be fatal for males in utero.[1],[2] This paper provides a literature review and an IP case report of a 16-year-old female who presented to our pediatric dental clinic where we managed her dental concerns. This report has been cleared for publication by the School of Dental Medicine. Parents gave both written and verbal consent for the use of patient-related documentation and information for the purpose of publication and no identifiers are disclosed in accordance with HIPAA guidelines.

 Case Report

A 16-year-old female was referred to our pediatric dental clinic by her primary care provider for a chief complaint of pain in the upper and lower left teeth while eating. The patient was 5'11” with a weight of 268l bs (body mass index 37.4, >99th percentile) and blood pressure of 106/60 mmHg. Her body temperature was 37.2°C and SpO2 was 100%.

Reported history (birth, social, and developmental)

The patient was born in Peru (6.5 pounds) through normal vaginal delivery to a G1P1 woman. At birth, hydrocephaly, cephalomegaly, pigmentation, and blisters on the left side of her face-neck along with “wire-like” or “wooly” texture of hair were reported. The pigmentation appeared whorled following the Blaschko's lines (lines in the skin indicative of cell development, not seen in normal healthy individuals) and increased in intensity [light-colored to verrucous dark-colored, [Figure 1]a as patient aged. No family history of similar findings was reported. The patient demonstrated cognitive and developmental delays (started walking at age 3). Patient's family moved to the US as undocumented immigrant and hence, any medicodental treatment would be done primarily on emergency basis (family had no financial support).{Figure 1}

Neurologic findings

When the patient was 14 years of age, she presented to the neurology clinic subsequent to having a seizure. The patient was diagnosed with generalized tonic–clonic seizures with postictal headache and weakness and placed on the antiseizure medication (levetiracetam, 500 mg/day). The patient was found to be neurologically alert and responsive. At age 14, she had a head circumference of 69.8 cm before a ventriculoperitoneal shunt was placed, and after placement, head circumference reduced to 68.5 cm (normal range: 54–57 cm). She had an increased fullness on the left side of her face with normal facial muscle function [Figure 1].

A magnetic resonance imaging of her brain demonstrated the abnormalities with findings suggestive of left hemimegalencephaly. In addition, there was evidence of an Arnold–Chiari malformation I [cerebellar tonsils herniated 2 cm below foramen magnum, [Figure 1]c. The maxilla appeared triangular in configuration and demonstrated linear defect (cleft) extending through the alveolar bone and hard palate between the maxillary right central and lateral incisor [Figure 1]d.

Orthopedic findings

The patient had significant scoliosis since her early teenage years with an exaggerated curve in her cervical spine. She was wheelchair bound, and pes planus and genu valgum were noted by the orthopedists.

Orofacial findings

Facial extraoral examination revealed the left-sided hemihypertrophy with generalized hyperpigmented whorls along the Blaschko's lines exclusively on the left side [Figure 1]a. The posteroanterior skull view demonstrated maxillary and mandibular hemihypertrophy [Figure 1]b. Extraoral facial midline was not coincidental with intraoral midline [Figure 2]b and [Figure 3]a.{Figure 2}{Figure 3}

Intraoral soft-tissue examination revealed gingival hyperplasia with a high-arched palate with the left-sided hemihypertrophy of tongue. In addition, enlargement of the filiform papillae on the left side of tongue was noted [Figure 3]b. The patient had a history of traumatic fibroma due to chronic tongue biting while seizure.

Intraoral hard-tissue examination revealed that the generalized spacing between the teeth along with a midline shift of 10 mm to the right and the occlusal plane was accentuated [Figure 2]a. The size of the teeth was larger (wider) on the left side (~1.2X times) compared to corresponding teeth on the unaffected right side [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e. Clinical examination revealed that the patient had an adult dentition except for missing third molars and #29 [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e. Severe halitosis was reported by parents which was due to minimal tooth brushing by the patient.

Radiographic examination revealed the presence of generalized supra/subgingival calculus with no interproximal carious lesions. Due to patient's significant macrocephaly (and increased facial dimension) and cervical kyphosis, it was not possible to obtain a panorex that included both the sides of patient's face. Hence, it was necessary to take two images with different angle/focus for each side. The images were then superimposed to obtain a readable image. Impacted teeth #1, #17, and #32 were seen with a conical crown of #1. Tooth #29 appeared impacted and possibly resorbing the roots of #30 [Figure 4]. Occlusal caries were noted on #14, #15, #18, #19, and #20. The patient was determined as high caries risk based on risk factors including as follows: socioeconomic status, diet history, oral hygiene, medical history, and lack of a dental home.{Figure 4}

Dental treatment

The patient never had a dental home. She was wheelchair bound and had a hard time sitting in the dental chair as any minor reclineation of the chair would trigger excruciating the neck and back pain. All dental care, including scaling and restorative dentistry, was completed with the patient seated in her wheelchair. The patient was appropriately referred to oral surgery for extractions and periodontics for subgingival scaling and root planning. Restorations were completed under local anesthesia and rubber dam isolation. The patient was not cooperative for restorative visits (F2: Negative behavior, Frankl rating). Despite our efforts to bring the patient back for follow-up care, she had only come for one follow-up appointment in subsequent 3 years. During this visit, we noted a new small carious occlusal pit, but improved oral hygiene.

Literature review

The condition was first described by A. E. Garrod in 1906.[3] It was named due to the histopathological characteristic and the presence of melanin pigment in the connective tissue cell layer, where it had been taken up by melanophores. Bloch (1925) and Sulzberger (1928) published cases with similar cutaneous manifestations.[3] IP manifestations include cutaneous lesions characterized by swirled hyperpigmentation along the Blaschko's lines with sparse, coarse hair. Cutaneous and noncutaneous manifestations of IP are summarized in [Table 1].[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] Mendelsohn first described the orodental findings of IP[3] which included hypodontia, delayed eruption in both dentitions, and “peg-shaped” teeth.[9] A review of 40 IP cases revealed that approximately 75% of IP cases exhibited the presence of orodental findings.[1]{Table 1}

Landy and Donnai in 1993 published diagnostic criteria for IP with emphasis on cutaneous findings as major criteria along with other findings as minor criteria.[4] Genetic basis for the development of IP has been extensively studied by Berlin et al.[7]IKBKG gene (2.8 kb, previously known as NEMO) is located on Xq28 and encodes a 419 amino acid protein, nuclear factor-kappa B (NFkB), or IKK-gamma. This NFkB (IKK-gamma) forms complex: IKK-alpha with IKK-beta. NFkB controls the expression of other genes involved in cell proliferation, immunity, and inflammation. In IP, this deletion of the 11.7 kb portion in the IKBKG (exon 4–10), leads to a downregulation of NFkB, which leads to increased apoptosis (cell death).[2],[7] However, the IKBKG mutation was not added to the list of diagnostic criterion. IP is also characterized by some noncutaneous features. Therefore, in 2014, Minic et al. published a comprehensive analysis of additional diagnostic features of IP which appears to encompass the vast majority of all previously described features within this clinical condition.[8] Minic et al. expanded the use of cutaneous lesions as an IP major diagnostic criteria and suggested using dental, ocular, hair, nail, palate, breast, and central nervous system as minor diagnostic criteria [Table 2].[4],[8] History of multiple male miscarriages, histopathologic features of IP, IKBKG mutation, and family history of similar condition could be used as additional criteria for IP diagnosis.[2] Targeted mutation analysis can be used to identify the most commonly occurring IKBKG deletion. If IP is suspected to be due to duplication or deletion of a less well-known portion of IKBKG gene, a skin biopsy should be considered. Histopathologic examination of biopsy sample would reveal hallmark features, melanin granules with large amount of eosinophilic infiltration in the dermis.[2] Once the diagnosis is made, genetic screening of all first degree relatives would prove helpful to rule out other affected individuals. A physical examination would provide more evidence for affected individuals. It is important to note that the patients can be diagnosed with IP regardless of failure to identify IKBKG gene deletion.[2] IP cases have been reported as a sporadic mutation due to the high mutation rate.[2] Kim et al. reported that unaffected parents might demonstrate germline mosaicism.[1] The hemifacial presentation of the condition in our case could suggest early chimerism (two different gene pools, one with IP and one without). Due to the hallmark clinical features in this case, it would be valuable to have a genetic diagnosis. However, funding was not available for the laboratory tests (dental care was done through charity care provided by the School of Dental Medicine). Therefore, the diagnosis was based on the clinical features with the knowledge that the genetic diagnosis may have helped understand the etiology and pathophysiology of the mutation.{Table 2}

IP is thought to be primarily embryonically lethal in the male fetus and that reports suggesting that only 5% of male fetus survive.[1] Conditions such as Klinefelter syndrome (XXY) are a common genetic finding,[2] yet the finding of males surviving to birth with IP is not that common. Due to high rates of fetal demise for a male fetus, a history of multiple miscarriages is commonly reported in IP.[2] In the presented case, the mother reported no history of frequent miscarriages and the patient's older brother is medically healthy [See pedigree chart in [Figure 3]c. Various studies documented variable ratios of affected females versus males 37:1,[11] 20:1,[1] and 14:1.[13] However, from one of the reports of 653 valid clinically identified IP cases, it was clear that IP affects individuals from all races.[16] There are no reports with documented differences in clinical findings between affected male versus female.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]

Dental findings are observed in approximately 54%–75%[9] of IP cases. Commonly reported orodental findings are delayed eruption, hypodontia, and “peg-shaped” teeth affecting both primary and secondary dentitions.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] Minic et al. reviewed articles published between 1993 and 2010 to systematically report orodental findings.[9] The group reviewed 1286 reported IP cases and concluded that the total number of dental and oral anomalies in each patient were more than 1 (1.67). The reported dental anomalies were shape deviations (36.4%), oligodontia (31.2%), and delayed eruption (17.8%). In addition, oral anomalies included high arched (“gothic”) or cleft palate (30%). Interestingly, surviving male IP patients have almost 50% chances of having high arched or cleft palate. One study also reported submucosal clefts.[13] Although some studies documented normal enamel and dentin structure in patients with IP,[3],[9],[15] one study reported enamel pitting or hypoplasia and hypocalcification.[13] Another study employed microanalytical tools to study the enamel structure and demonstrated that IP could significantly affect mineralization of enamel, but comparatively found no impact on the mineralization of dentin.[14] Uncommon reported dental findings include impacted maxillary canine and mandibular teeth,[13] maxillary and mandibular hypoplasia, or hemiatrophy.[9] Motamedi et al. reported the presence of talon cusp as one of the dental finding in IP.[10]

Here, the case presented demonstrated cutaneous, eye, hair, and dental findings. Majority of the findings were present on the left side of body. It is important to note that the most commonly reported dental findings such as hypodontia or oligodontia were not evident in our case. In addition, information regarding a delay in eruption of primary or permanent teeth could not be conclusively recalled by the patient's mother. The most commonly reported size variation was seen in our patient as well. It was manifested as “tulip-shaped” (comparatively larger crowns and smaller roots) teeth, but only on the affected left side. This type of hemifacial effect has not been reported previously. Teeth size variation between the affected and unaffected side was clearly evident in this case. Although minor variations in arch width and facial width on the right versus the left side have been documented in IP cases,[16] no reports documented hemifacial or tongue hypertrophy. In this reported case, we noted both hemifacial and tongue hypertrophy on the left side. Hemiatrophy of maxillary and mandibular arches has been reported in IP cases;[16] however, the substantial variations in arch widths, as evidenced in our case, have not been previously reported. We also noted additional orodental findings of IP such as “gothic” or high-arched palate, impacted mandibular teeth, palatal cleft (between #7 and #8), and diastema.

Cutaneous lesions in IP usually resolve by second or third decade of life. However, these lesions can be easily confused with other conditions especially if no family history of IP is known. Such conditions include epidermolysis bullosa, dermatitis herpetiformis, herpes zoster, bullous impetigo, and focal dermal hypoplasia. All these are distinct entities and histological examination can confirm IP diagnosis. X-linked hypohidrotic ectodermal dysplasia and immune deficiency and X-linked hypohidrotic ectodermal dysplasia with immune deficiency, osteoporosis, and lymphedema can be included in differential diagnosis of IP. However, both these conditions commonly occur in males, and NFkB function in these conditions may be impaired but not absent (as in IP).[2] In addition, some of the conditions which can follow the Blaschko's lines are presented in [Table 3] along with the features that distinguish them from IP.[2] It is important to note that some of the findings in our patient match with that of Hypomelanosis of Ito (mosaicism characterized by hypopigmentation along the Blaschko's lines) such as scoliosis, hemimegalencephaly, and abnormal head circumference. However, hyperpigmentation confirmed the diagnosis of IP in our case. Furthermore, variable findings in IP are common, and additional gene mutations have been suspected to be present coincidentally for large phenotypic variation.[7]{Table 3}

Scheuerle and Ursini provided comprehensive information regarding management of IP affected individuals or children.[2] Multisystem involvement in IP would warrant a multidisciplinary management approach involves as follows: geneticist for counselling, pediatric dermatologist for management of cutaneous, hair and nail problems, pediatric neurologist for the management of seizures, pediatric ophthalmologist for the management of retinal hypervascularization or other ophthalmic problems, developmental pediatrician for the developmental or intellectual delay, pediatric dentist for the management of dental problems, and a craniofacial team for repair of clefts. It is important to note that none of the specialties have established guidelines for the management of patients affected with IP or other similar conditions. Regular follow-up is the only guideline mostly recommended by researchers and providers who frequently manage IP cases. Consistent with previous reports, our patient was managed by a team of developmental pediatrician, pediatric neurologist, pediatric dentist, periodontist, and oral surgeon. The patient positioning in the dental chair and panorex machine was a challenge due to the fact that the patient was obese and had Arnold–Chiari malformation I. Minor backward bending of the neck would cause excruciating pain to the patient. This could be a great concern for anesthesia and would possibly pose a significant problem for intubation. The patient was borderline cooperative, and hence, the most treatment was completed in her wheelchair with adequate neck support. Medical complexity warranted customized care for this patient. Due to family's immigration status, social, and financial issues, this patient was lost to follow-up. Multiple attempts were made to schedule the patient for follow-up; however, the limited family resources undermined the ability of the team to provide care.

There are still a few unanswered questions as to what is the role of NFkB in expression of full phenotypic features especially morphodifferentiation and eruption delay in IP. In addition, how IP features can be expressed on only one side of the body needs to be investigated. To understand this pathophysiology, mice deficient in Nemo (IKBKG) were generated using gene targeting. This mouse model could have served for understanding the phenotypic expression of IP in mice and extrapolating the information to humans for further research. However, the mice embryos could not survive past 13.5 days after gestation. The fatality was due to tumor necrosis factor alpha-mediated apoptosis in liver and resulting liver damage.[17] In addition, female mice heterozygous for Nemo (IKBKG) were shown to have skin lesions similar to human lesion in IP.[18] Hence, the murine model can serve a valuable tool for future studies.


This is the first case of IP with hemifacial and tongue hypertrophy with tooth size and shape discrepancy between affected and unaffected side. Developmental and intellectual delay coupled with challenging social issues made the care and cooperation of this patient and family difficult and ultimately resulted in the patient being lost to follow-up. Hypertrophy of tongue and jaw has the potential to anatomically alter airway and inability to extend neck might pose challenges to the intubating patient for general anesthesia. Dental anomalies in IP cases may require esthetic or orthodontic corrections. Overall, a multiorgan problem needs a customized multidisciplinary care plan.

Important note

Further information can be found at the National Institute of Neurological Disorders and Stroke and IP International foundation websites which provide support for research and medical care of patients with IP.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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