Melanin Incontinence, Infantile Stroke, and Negative Genetics in a Case of Incontinentia Pigmenti

A 7-year-old girl presented with diffuse skin lesions since birth (initially, reddish blisters over the trunk and limbs in a linear pattern) and right focal seizures followed by right hemiparesis from 5 months of age. She had mild deficits in socio-adaptive skills (Social Quotient- 64). There was no family history of similar illness. Examination revealed linear hyperpigmentation following lines of Blaschko, strabismus, hypodontia, and right hemiparesis [Figure 1a–c]. Fundus examination was normal. Magnetic resonance imaging of the brain and angiography showed left frontoparietal and right frontal gliosis with attenuation of left middle cerebral artery (MCA) [Figure 2b–f]. Skin biopsy showed melanin incontinence with no eosinophilic infiltration [Figure 2a]. A diagnosis of incontinentia pigmenti (IP) with stroke was considered.[1,2] Targeted deletion–duplication analysis for IKBKG gene via Multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing were negative. IKBKG exon 4–10 deletions are found in 75.1% cases, point mutations in 22.1% cases, locus rearrangement in 3.6% cases, and no alterations in 4.9% patients.[3] Although Sanger sequencing and long-read amplicon sequencing were not performed, the histopathology and clinical features clinched the diagnosis. Bloch–Sulzberger syndrome is a rare X-linked dominant genodermatosis with involvement of ectodermal tissues- skin, central nervous system, eyes, hair, nails, and teeth.[2] Stroke mechanism is attributed to small vessel disease (SVD) due to endothelial cell damage secondary to Nuclear factor kappa B (NF-κB) inactivation.[4] Left MCA attenuation was noted in our patient, contrasting the more common SVD hypothesis. This case highlights the role of skin biopsy in cases where genetic analysis is negative.

Figure 1.

(a) Hyperpigmentation along the lines of Blaschko (Stage 3 of IP) noted over the back. (b) Hyperpigmentation along the lines of Blaschko over the posterior aspect of thighs and legs. (c) Hypodontia (no conical/abnormally shaped teeth were seen). IP: incontinentia pigmenti

Figure 2.

(a) Skin biopsy (HE, ×400) shows melanin incontinence in the superficial dermis (white arrow). (b) Sagittal FLAIR MRI depicting atrophied corpus callosum (yellow arrow). (c) Coronal FLAIR MRI showing left frontal encephalomalacia with gliosis along the corticospinal tract in the internal capsule and ipsilateral hemi crus atrophy. (d) and (e) Axial FLAIR MRI showing cystic encephalomalacia with gliosis in the left frontoparietal and occipital lobes with ex vacuo dilation of the left lateral ventricle as well as right medial frontal gliosis. (f) TOF MR angiography depicting attenuation of left middle cerebral arterial M2, M3 branches. FLAIR: fluid attenuated inversion recovery, HE: hematoxylin and eosin, MR: magnetic resonance, MRI: magnetic resonance imaging, TOF: Time of flight

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