A case of familial incontinentia pigmenti in infancy without hyperpigmented stage.

To the editor: Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal disorder primarily caused by mutations in the IKBKG (NEMO) gene. Cutaneous manifestations of IP typically progress through four stages: inflammatory (or vesicular) stage, verrucous stage, hyperpigmented stage, and hypopigmented (or atropic) stage.1 Throughout the disease course, most cases develop linear or whorled brownish reticular pigmentation following the lines of Blaschko. Additionally, some patients experience linear hypopigmentation and absence of hair, usually during adolescence. Here, we report a rare manifestation of this disease. A six-month-old female infant (the proband) was born with erythemas and erosions (Figure 1A, B). Neonatal ophthalmologic screening revealed familial exudative vitreoretinopathy. The skin lesions gradually healed within a few days, followed by the development of hypopigmentation mainly on the trunk and head, accompanied by alopecia (Figure 1C–E). The mother exhibited erythematous vesicles three days after giving birth, which resolved by the time she reached one year old, leaving residual hypopigmentation and alopecia on the crown of her head (Figure 1F, G). Other family members showed no abnormalities. Notably, the patient did not develop the hyperpigmented stage, which is observed in most IP cases (90‒98%).2, 3 Hyperpigmentation is characterized by lesions that are independent of inflammation and do not correlate with the location of the previous stage. Typically, hyperpigmentation appears within the first few months of life, gradually fades before adulthood, and may result in residual lesions in a few individuals. Besides, the patient presented with hypopigmentation during the neonatal period. Next-generation sequencing and Sanger sequencing identified a heterozygous nonsense mutation, c.388C>T (p. Arg130*), in exon 2 of the IKBKG gene in both the mother and daughter (Figure 1H, I). The reported variant was predicted to induce nonsense-mediated mRNA decay.4 However, the variant was not found in the maternal grandparents (Figure 1J, K), indicating that the mother's variant was de novo. Furthermore, the sequencing chromatogram of the mother (Figure 1I) showed a different waveform for c.388 compared to her daughter (Figure 1H). The peak corresponding to the mutant single nucleotide site in the mother was significantly lower than the wild type. Considering this abnormal peak of the mother and her mild phenotype, we suspected she was a mosaic. In this study, we have unveiled an uncommon phenotype of IP, highlighted the broad spectrum of clinical manifestations, and provided valuable insights for clinical diagnosis. We would like to thank the patient and her family. This work was supported by the National Nature Science Foundation (82073422 and 82273504) and the Shanghai Municipal Natural Science Foundation (22ZR1440800). The parents of the patient have given written informed consent. The authors declare no conflict of interest.