Clinical case of Bloch — Sulzberger syndrome

Purpose.To present a clinical case of Bloch Sulzberger syndrome. Material and methods. The examinations were performed to diagnose the disease: а visual examination of the skin, cytological analysis of the gallbladder fluid, general and biochemical blood tests, genetic research. Results.During a visual examination of the skin, a differential diagnosis was made with infectious dermatitis, toxic-allergic dermatitis, epidermolysis bullosa and linear IgA-dependent dermatosis in children. Crucial in the diagnosis belonged to a genetic study, after which a deletion of exons 410 of the IKBKG gene was detected, which confirmed Bloch Sulzberger syndrome. Conclusion.Newborns with vesicle-bullous rashes entering the neonatal pathology department and observed by neonatologists require a thorough examination, a mandatory consultation of a dermatologist inorder to determine further management tactics.

UNRAVELING INCONTINENTIA PIGMENTI: A COMPARISON OF PHENOTYPE AND GENOTYPE VARIANTS

BACKGROUND Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that predominantly affects the skin, beginning with a characteristic linear vesicular rash shortly after birth. Multisystem abnormalities can further be seen in hair, nail, ocular, dental, and central nervous system. Although most affected individuals carry a common pathological deletion of the IKBKG gene, approximately 20% have no molecular confirmation. There remains a lack of understanding of phenotypic variations between mutation positive and negative patients with IP. OBJECTIVES We aim to 1) Describe clinical characteristics, phenotype, and genotype of patients with IP, and 2) Compare clinical differences between mutation positive and negative cohorts. DESIGN/METHODS A retrospective chart review was conducted at a large tertiary paediatric centre from January 1990 to June 2017, for children under 19 with a clinical diagnosis of IP by a paediatric dermatologist or geneticist. Baseline characteristics, diagnostic history, family history, cutaneous and extracutaneous symptoms were extracted. Further subspecialty reports such as dental and ophthalmology, and available laboratory results including bloodwork, histopathology, and genetic reports were reviewed. Patients who had undergone molecular genetic testing were further divided into either positive (IKBKG mutation) or negative (no identifiable mutation) genetics cohorts for analyses. RESULTS A total of 44 children with IP were identified, including 79% female, 64% white (non-hispanic), 24% with IP family history, and 85% were confirmed on biopsy. Median age at first dermatology or genetics consult was 6 weeks and 26% had undergone a full septic workup (cultures negative) prior for the IP rash. Extracutaneous involvements were common: dental (49%), ocular (32%), hair (31%), nail (15%), and neurodevelopmental (24%). Compared to the mutation positive (59%) cohort, those with negative mutations (41%) were significantly more likely to be male, have a negative family history of IP, and lower incidences of dental and hair anomalies (P <0.05). CONCLUSION Clinical approach to IP should involve not only dermatology and genetics evaluation, but may benefit from multidisciplinary monitoring for extracutaneous manifestations. Findings of unique clinical variations between positive and negative mutation cohorts suggests the need for further in-depth evaluation into key differences as they may affect disease counselling and future prognosis.

A novel frameshift mutation of the IKBKG gene causing typical incontinentia pigmenti

Introduction. Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis. Mutations of the IKBKG gene are responsible for IP. A deletion of exons 4-10 can be found in 80% of patients with IP. There are 69 different mutations of the IKBKG gene that have been reported. Case Outline. A proband, female patient from a family without previously diagnosed IP is reported. She had skin and dental changes typical of IP. The diagnosis was made according to updated IP criteria. Pathohistological and ultrastructural analysis of skin biopsy confirmed the diagnosis. However, the common deletion of exons 4-10 in the IKBKG gene could not be detected. Sequencing revealed the indel (deletion/insertion) mutation c.641_647delGCATGGAinsAT (p.Arg214HisfsX38) in exon 5 of the IKBKG gene. Because this mutation could not be detected in the unaffected mother of the proband, it seems to be a de novo mutation. Conclusion. The registered novel frameshift IKBKG mutation c.641_647delGCATGGAinsAT (p.Arg214HisfsX38) can be considered to be the cause of IP in this case.

Incontinentia Pigmenti in an XY Boy: Case Report and Review of the Literature

Background: Incontinentia pigmenti (IP) is a rare genetic skin disorder with X-linked dominant inheritance and a characteristic sequence of cutaneous manifestations, which is regarded as lethal in XY males. Objective: To report a case of a surviving XY male with the common IKBKG (NEMO) gene deletion confirming IP. Methods and Results: A newborn XY male with suspected IP underwent a skin biopsy on affected tissue for histopathology. Molecular genetic testing was also performed on the specimen and revealed the common IKBKG gene deletion with a pattern suggestive of somatic mosaicism. Our findings are aligned with a PubMed literature review for XY males with IP and documented IKBKG mutation. We determined that only 10 such genetically proven cases have been reported, including our case. Conclusion: Although relatively rare, cases of IP in XY males with the common NEMO mutation have likely been underreported due to the unavailability of appropriate testing in the past. Karyotype and molecular testing should be considered when clinical suspicion of IP arises for a male patient.

First IKBKG gene mutation study in Serbian incontinentia pigmenti patients

Introduction. Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis. Mutations of the IKBKG gene are the only known cause of IP. The presence of other than skin changes is important in the diagnosis of atypical IP cases when skin changes are discrete. Objective. The study was designed to analyze clinical manifestation, family histories and the frequency of IKBKG gene mutation in IP patients in Serbia for the first time and to compare them with other reported findings. Methods. Two Serbian unrelated families with eight female subjects were investigated. Blood samples were used for IKBKG exon 4-10 deletion testing using modified PCR protocol. For probands pathohistological and ultrastructural analyses of skin biopsies were done. Results. Positive clinical diagnosis according to IP criteria was present in seven cases. In six of them, including probands, positive molecular gene testing for IKBKG exon 4-10 deletion was present. Conclusion. This is the first report of genetically confirmed IP in two Serbian families. The IP patients presented a common IKBKG exon 4-10 deletion. The frequency and type of IKBKG mutation found in investigated IP patients in Serbia were similar to results of other studies. Various clinical features of investigated patients have allowed us to demonstrate that molecular genetic testing which specifically detects the common IKBKG mutations, the only known cause of IP, is useful in diagnosing IP especially in mild or atypical cases. The molecular genetic testing of the IKBKG mutations may be helpful for rapid confirmation of IP diagnosis, prenatal diagnosis and carrier detection.