Challenges in Rare Diseases Diagnostics: Incontinentia Pigmenti with Heterozygous GBA Mutation

Rare diseases represent a diagnostic challenge due to their number, variety of clinical phenomena, and possibility of a simultaneous presence of two or more diseases. An illustration of this challenge is an occurrence of a late diagnosis of a proband initially diagnosed with West syndrome, later revealed to be caused by Incontinentia pigmenti (IP). Furthermore, 20 years later, it was discovered that the proband was also a carrier of a heterozygous GBA gene mutation. The methods used in diagnostics were as follows: IKBKG gene analysis, the X-chromosome inactivation assay, analyses of the genes relevant for neurodegeneration, WES analysis, analysis of biochemical parameters typical for Gaucher disease (GD), and autoantibodies including IFN-α2a and IFN-ω. To avoid overlooking IP and other possible rare disease diagnoses, carefully searching for dermatological signs in these conditions is recommended. It is important that the diagnostic criteria are based on quality and extensive data from multiple studies of each rare disease. Establishing precise diagnostic criteria for as many rare diseases as possible and establishing a publicly accessible database of rare diseases with a search possibility according to phenotypic abnormalities and genetic mutations would greatly facilitate and speed up the establishment of an accurate diagnosis.