Dr Jerin.K.John, Dr Sheela Nampoothiri (Genetics Dept, AIMS),
Dr Dhanya Yesodharan (Genetics Dept, AIMS),
Dr C. Jayakumar (Pediatrics)
A 3-year female child born at term of non-consanguineous marriage presented at 3 years of age with a history of raised erythematous rashes over upper and lower limb at birth. The eruptions, consisting of erythematous papules and vesicles, spread to her extremities and trunk in a pattern consistent with Blaschko’s lines.
A thorough physical examination revealed that the scalp, hair, nails, and oral mucosa were all normal.
She currently has a streaky hyperpigmented macules over the leg.
Child has attained all age-appropriate milestones. She has history of seizure from 14 th day of life and is on Levetiracetam Ophthalmology evaluation done showed retinal detachment on right eye and left side optic atrophy.
Multiple ligation-dependent probe amplification (MLPA) done showed heterozygous deletion in exon 2 and 3 of IKBKG.
X linked dominant variant IKBKG is located on the chromosome band Xq28
Discussion:
Incognita pigmenti(IP) is a X linked dominant condition with incidence of 0.7 case per one lakh birth. Male foetuses die inutero
The syndrome involves ectodermal and mesodermal tissues. The manifestations, though in majority of cases involve skin, there may be extracutaneous manifestations also. The progression of skin manifestation occurs in four phases which may be concomitant or sequential.
Stage 1
There is vesicular eruption, which is followed hyperkeratotic, verrucous linear plaque. Stage 2
Consists of Hyperkeratosis, acanthosis, papillomatosis with dyskeratotic keratinocytes.
Stage 3
There is greyish blue hyperpigmentation, distributed in Blaschko’s lines or in swirling pattern.
Stage 4
There are hypopigmented linear macules with no skin appendages on the trunk or limb, appearing in adulthood.
According to some, there are only three phases as fourth phase may appear later and remains underdiagnosed
The skin appearance may mimic congenital syphilis, TORCH infection in the first phase; epidermolytic hyperkeratosis and lichen striatus in second phase; nevoid hypermelanosisdermatopathiapigmentosa reticularis, X- linked chondrodysplasia punctata in third phase; and hypomelanosis of Ito and congenital aplasia cutis in fourth phase.
Extracutaneous manifestations include CNS (seizure, mental retardation, ischemic cerebrovascular accidents, hydrocephalus), eyes (strabismus, cataract, anophthalmia, microphthalmia ), teeth ( hypodontia and partial adontia), bone and musculoskeletal system (syndactyly, skull deformity, supernumerary ribs, hemiatrophy and shortening of legs and arms).
It is caused mutation in NF kappa B essential modulator (NEMO) gene of kappa B genetic factor (nuclear kappa B essential modulator) located in q28 portion of X chromosome. Eighty per cent patients have a deletion of exons 4 and 10 of NEMO gene.
Management is mainly supportive and based on symptomatology alone.
Though the skin manifestations regress spontaneously, the neurological and dental anomalies usually appear later in childhood, thus justifying continued follow up. In our case, there were vesicular eruptions, followed hyperkeratotic, verrucous linear plaques.
The reason for reporting the case is the rarity of this disease and the diagnostic dilemma it may pose because of its similarity in presentation with congenital syphilis.
Carry home message
IP is a very rare genodermatosis. It should be suspected where other common causes are excluded. But, one should be aware of the typical manifestation to diagnose it early and also to ensure regular follow up. As females can have very subtle clinical manifestations of IP, mothers of children with IP should undergo genetic testing to identify their carrier status so that appropriate counselling and prenatal testing can be offered in subsequent pregnancies.