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Background PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated with 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. Objectives To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. Methods Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. Results MiTES presents in the first year of life; in all cases the condition regresses over the first decade, leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12 CIP are rarely found. The genotype–phenotype study of the PRDM12 polyalanine tract shows that having 7–15 alanines is normal; 16–18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. Conclusions We provide diagnostic criteria for MiTES and improved longitudinal data. MiTES and CIP are distinct phenotypes, despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells. We hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter‐induced AD exacerbations from wildfires to the potential for indirect effects like drought‐induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long‐term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population‐level trends. [ABSTRACT FROM AUTHOR]

Byline: Sandipan. Dhar, Sahana. Srinivas Psoriasis is a common, chronic, immune-mediated, multisystem, inflammatory disorder. It affects all age groups, including infancy. In one-third of the cases, the onset of the [...]

Background: Filaggrin (FLG) gene encoding the protein filaggrin plays an important role in barrier function of the skin and its alteration is a predisposing factor for atopic dermatitis. FLG gene variants result in absent or decreased filaggrin protein. Worldwide, the prevalence of FLG variants ranges from 14 to 56%. FLG null variants are distinct in each population. Objectives: To study the FLG gene polymorphisms in Indian children and attempt a genotype-phenotype correlation in atopic dermatitis. Methods: This was a cross-sectional, multicentre study conducted on 75 Indian children. Demographic details, clinical features and identified FLG null variants were recorded. We performed a whole gene sequencing of the entire FLG coding region using next-generation sequencing technology. Results: The prevalence of FLG null variants was 34.7%. A total of 20 different FLG loss of function variants in 26 children were documented. Sixteen (80%) variants were novel and four (20%) were previously reported in Asian and European populations. We found a statistically significant association between FLG variants with early age of onset of atopic dermatitis (P = 0.016) and elevated serum IgE levels (P = 0.051). There was no significant difference between atopic dermatitis phenotypes in children having one variant as compared to children harbouring two or more null variants. Limitations: Small sample size. Conclusion: Our study reports a unique set of FLG variants different from Asian and European populations, with these variants being significantly associated with an early age of onset of atopic dermatitis and elevated serum IgE levels. [ABSTRACT FROM AUTHOR]

Byline: Sandipan. Dhar, Abhishek. De, Sahana. Srinivas Introduction: Treatment of moderate to severe atopic dermatitis (AD) is a real challenge for the dermatologists. Dupilumab is the first targeted biologic therapy [...]

Byline: Sahana. Srinivas, G. Pradeep Sir, Congenital chikungunya infection presenting at birth is rare and poses a diagnostic challenge. We describe a newborn with congenital chikungunya infection presenting with extensive [...]

Congenital atrichia a rare form of alopecia in children, presents with complete absence or sparse hair over the scalp and body, while the teeth, nails, and sweat glands are normal. Uncommonly, this hair abnormality can be associated with any systemic or cutaneous abnormalities. We report three cases of congenital atrichia with parental nonconsanguinity and central nervous associations such as developmental delay, spastic quadriparesis, failure to thrive, myoclonic seizures, and attention deficit hyperactivity disorder. The presence of papular lesions in two among the three children further supplemented our case report. Genetic analysis and counseling regarding the constancy of the condition will be the foremost important part of management. [ABSTRACT FROM AUTHOR]

Piebaldism is a rare genetic disorder of congenital leukoderma caused by mutation in KIT proto-oncogene receptor tyrosine kinase. We present a 10-year-old boy with congenital depigmented macules suggestive of piebaldism associated with café au lait macules and skin fold freckling complicating the diagnosis. A diagnosis of piebaldism was made via exome sequencing that showed a pathogenic variant of KIT gene with no pathogenic variants of NF1 or SPRED1 gene. Our current understanding of the KIT tyrosine kinase function may provide a better explanation into this phenotypic coexistence and does not necessarily represent an overlap with Neurofibromatosis type 1. [ABSTRACT FROM AUTHOR]

Progressive symmetric erythrokeratoderma (PSEK) is a rare hereditary disease of keratinization, characterized clinically by symmetric erythematous and hyperkeratotic plaques and genetically inherited as an autosomal dominant trait with variable expression and incomplete penetrance. The genetic basis is unclear, although a mutation in the loricrin gene (LOR) and rarely in the connexin gene (CON) has been described. We report a case of PSEK in which genetic analysis did not highlight mutations in the LOR gene, suggesting further genetic research into the etiology of PSEK. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome is a myeloproliferative disorder characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues. It is uncommonly seen in children. We describe a 14-year-old girl diagnosed with idiopathic hypereosinophilic syndrome presenting with recurrent, painful oral and genital ulcers, hepatosplenomegaly along with consistently high eosinophil count and leucocytosis. Genetic studies showed negative for FIPIL-PDGFRA fusion gene. Mucosal ulcers were recalcitrant to conventional therapy and responded well to thalidomide. [ABSTRACT FROM AUTHOR]

Byline: Sahana. Srinivas, Samipa. Mukherjee, Ravi. Hiremagalore Sir, Congenital erosive and vesicular dermatosis, first reported by Cohen et al . in 1985, is a rare disorder characterized by erosions and [...]