Snezana MinicUniversity of Belgrade, Serbia
Title: Challenges in rare disease diagnostics – Incontinentia pigmenti
Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare X-linked genetic disorder with an estimated prevalence of 1.2/100.000. It appears almost exclusively in females, being usually lethal in males. It is caused by a mutation of the IKBKG gene localized on the X chromosome, an intragenic deletion of IKBKG exons 4-10, which is the only gene known to be associated with IP. Clinical manifestations of IP occur as a consequence of enhanced apoptosis due to this mutation.
The most prominent clinical manifestations are skin changes, which represent major IP diagnostic criteria. Skin changes in IP occur along the lines of Blaschko throughout four stages. They are usually combined with dental, ocular and CNS anomalies - minor criteria. Non-skin changes can be of great prognostic and diagnostic value in cases where skin changes are discrete from their beginning or during their evolution.
The life span of the patients depends on minor criteria. CNS anomalies usually occur from neonatal through early infantile period and represent the most important threat to normal life of patients with IP.
Rare diseases represent a diagnostic challenge due to their large number and variety of clinical phenomena, and a possibility of the simultaneous presence of two or more diseases in a patient. In solving complex cases which meet criteria of more than one defined disease, more detailed genetic analyses such as NES and WES are recommended.
In order to avoid overlooking IP and other possible rare disease diagnoses, it is recommended to carefully search for dermatological signs in these conditions.
Establishing precise diagnostic criteria for as many rare diseases as possible, and an open access database of rare diseases in which it would be possible to search for disease according to phenotypic abnormalities and genetic mutations would greatly facilitate and speed up the establishment of accurate diagnoses.
Snežana Mini? graduated from the Faculty of Medicine at the University of Belgrade, obtained MD in 1986, and a PhD in 2001 on Incontinentia pigmenti clinical aspects, ultrastructural and cytogenetic analyses. Since 1988, she has been working at the Clinic of Dermatovenerology, University Clinical Center of Serbia, and Faculty of Medicine, University of Belgrade, both as a practitioner and a professor. She is the Associate professor of Dermatovenerology, chief of the Polyclinic’s department at the Clinic of Dermatovenerology, University Clinical Center of Serbia in Belgrade. Ever since the beginning of her career, she has been interested in hereditary diseases, specifically in Incontinentia pigmenti. She is a member of the European Academy of Dermatovenerology (EADV) and Serbian Society of Dermatovenerology.