Longitudinal Growth in Children With Epidermal Differentiation Disorders.

IMPORTANCEChildren with epidermal differentiation disorders (EDDs) frequently exhibit impaired growth, yet longitudinal growth trajectories across multiple EDD genotypes have not been systematically evaluated.

OBJECTIVETo characterize longitudinal growth outcomes, including height, weight, and head circumference, in children with EDDs and evaluate genotype-specific associations.

DESIGN, SETTING, AND PARTICIPANTSThis longitudinal cohort study of children with EDDs used registry-based survey data and pediatric growth measurements through age 18 years. Data were collected from June 2022 to June 2025 and analyzed in September 2025. Participants were recruited through the National Registry for Ichthyosis; growth data were analyzed using US Centers for Disease Control and Prevention/World Health Organization pediatric growth standards. A total of 135 individuals aged 30 years or younger from 129 kindreds with confirmed EDDs and 26 unaffected siblings from 20 kindreds were included. Participants were classified into 5 genotype-based groups: autosomal recessive nonsyndromic-EDDs (nEDD), SPINK5-syndromic EDD (sEDD), keratinopathic-nEDDs, FLG-nEDD, and STS-sEDD.

EXPOSURESThe primary exposure was EDD genotype. Secondary exposures included supplemental caloric intake, gastrostomy tube use, preterm birth, and neonatal intensive care unit admission.

MAIN OUTCOMES AND MEASURESPrimary outcomes were longitudinal height, weight, and head circumference percentiles from birth to age 18 years. Growth trajectories were analyzed using linear mixed-effects models, comparing EDD subtypes with population norms at monthly points within prespecified age intervals (age 0-24, 25-48, and >48 months).

RESULTSAmong 135 participants (62 female [45.9%] and 73 male individuals [54.1%]; mean [SD] age, 10.5 [6.8] years; 13 Asian [9.6%], 7 Black [5.2%], 9 Hispanic [6.7%], and 89 White individuals [65.9%]), mean weight and height were less than the 50th percentile during the first 24 months of life (weight, 31.4th percentile; P < .001; height, 39.0th percentile; P = .02), with no significant difference from the population median thereafter. Growth impairment depended on genotype: individuals with SPINK5 variants exhibited persistent deficits at age 25 to 48 months (weight, 17.7th percentile; P = .002; height, 6.8th percentile; P < .001), whereas early deficits associated with ABCA12 and KRT10 variants attenuated over time and were no longer statistically significant.

CONCLUSIONS AND RELEVANCEThe results of this cohort study suggest that growth impairment in EDDs depends on genotype and is most prominent during the earliest months of life. Routine growth monitoring should be standard of care, particularly for children with high-risk genotypes, such as SPINK5.

Abstract from PubMed