A Neonate with Linear Rashes Over the Trunk and Extremities with Alopecia (Answers)

Winner of the Clinical Quiz Dr. Rinku Sharma Post-graduate student (third year) University College of Medical Sciences, Guru Teg Bahadur Hospital, New DelhiQuestion 1: What is the diagnosis of the dermatological condition? Answer: The condition [Image 1-4] is incontinentia pigmenti (IP, OMIM#308300). Skin lesions are the first clinical sign manifesting in the neonatal period. These lesions pass through 4 stages. Stage 1 is vesiculobullous eruptions. In the next three stages, lesions evolve to become verrucous, hyperpigmented, and finally hypopigmented lesions which persist for life. The lesions follow Blaschko’s lines which form major diagnostic clinical criteria, minor criteria being the involvement of teeth (hypodontia, microdontia, etc.), hair (alopecia and woolly hair), nails, retina, and family history consistent with X-linked inheritance.[1]Image 1Image 2Image 3Image 4Question 2: What is the mode of inheritance? Answer: Mode of inheritance – X-linked dominant. Question 3: Which other organ systems are commonly affected in this condition? Answer: Neurological and ocular manifestations are most commonly associated. Neurological manifestations include seizures, developmental delay, and intellectual disability; ocular problems include retinal hypervascularization, retinal detachment, strabismus, cataracts, optic atrophy, retinal pigmentary abnormalities, and microphthalmia.[2,3] Question 4: Identify Image 5.Image 5Answer:Image 5 is depicting multiplex ligation-dependent probe amplification (MLPA) test. Since majority (65%) have large deletion in IKBKG gene, deletion/duplication analysis by MLPA should be performed first. Question 5: Which is the most common genetic variant? Answer: 11.7-kb IKBKG genomic deletion spanning from exons 4 to 10 is the most frequent IP mutation in 60%–80% of affected females causing a loss of function of IKBKG/NEMO.[4] Question 6: How do you counsel the family? Answer: Multidisciplinary consultations should be obtained. Symptomatic treatment for skin lesions, monitoring for cutaneous squamous cell carcinoma, and brain imaging to investigate occlusive consequences of IP are to be done. Morbidity and mortality depend on the severity of eye and neurological involvements. Genetic counseling is to be provided: though IP is inherited in an X-linked manner, about 65% result from a de novo pathogenic variant. While heterozygous women have a 50% chance of transmitting the IKBKG variant, males with somatic and germline mosaicism may transmit the IKBKG variant to daughters, not to sons. Male conceptuses with this variant are likely to undergo intrauterine demise. Pregnancies at increased risk may undergo prenatal testing. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.Comments by Dr. Ankita Patel (Section Editor) We received a good participation for the quiz but mostly the answers were partially correct. No one answered the counseling part perfectly. Some mentioned about the genetic counseling but forgot to mention about the counseling for the management of the current case. With the heavy load in outpatient department and inpatient department, clinicians often miss on the counseling part which is an important aspect of practice.