{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:07:41Z","timestamp":1790784461315,"version":"4.1.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"abstract":"\n Importance<\/jats:title>\n Children with epidermal differentiation disorders (EDDs) frequently exhibit impaired growth, yet longitudinal growth trajectories across multiple EDD genotypes have not been systematically evaluated.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To characterize longitudinal growth outcomes, including height, weight, and head circumference, in children with EDDs and evaluate genotype-specific associations.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This 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),\n SPINK5-<\/jats:italic>\n syndromic EDD (sEDD), keratinopathic-nEDDs,\n FLG<\/jats:italic>\n -nEDD, and\n STS<\/jats:italic>\n -sEDD.\n <\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n The primary exposure was EDD genotype. Secondary exposures included supplemental caloric intake, gastrostomy tube use, preterm birth, and neonatal intensive care unit admission.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary 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 &amp;gt;48 months).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 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;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; height, 39.0th percentile;\n P<\/jats:italic>\n \u2009=\u2009.02), with no significant difference from the population median thereafter. Growth impairment depended on genotype: individuals with\n SPINK5<\/jats:italic>\n variants exhibited persistent deficits at age 25 to 48 months (weight, 17.7th percentile;\n P<\/jats:italic>\n \u2009=\u2009.002; height, 6.8th percentile;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), whereas early deficits associated with\n ABCA12<\/jats:italic>\n and\n KRT10<\/jats:italic>\n variants attenuated over time and were no longer statistically significant.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n The 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\n SPINK5<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamadermatol.2026.3782","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:32:01Z","timestamp":1790782321000},"source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Growth in Children With Epidermal Differentiation Disorders"],"prefix":"10.1001","author":[{"given":"Caroline","family":"Echeandia-Francis","sequence":"first","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela J.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra V.","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany X.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Sirotich","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riddhi D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Ossowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, Karol Jonscher University Hospital, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geliang","family":"Gan","sequence":"additional","affiliation":[{"name":"Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Paller","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Choate","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Genetics, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"doi260045r1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2015-212610","article-title":"Short stature with congenital ichthyosis.","volume":"2015","author":"Lakhani","year":"2015","journal-title":"BMJ Case Rep"},{"issue":"1","key":"doi260045r2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jpeds.2004.03.052","article-title":"Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure.","volume":"145","author":"Moskowitz","year":"2004","journal-title":"J Pediatr"},{"issue":"7","key":"doi260045r3","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3432","article-title":"Genetics of inherited ichthyoses and related diseases.","volume":"100","author":"Fischer","year":"2020","journal-title":"Acta Derm Venereol"},{"issue":"4","key":"doi260045r4","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1093\/bjd\/ljaf154","article-title":"Nonsyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy.","volume":"193","author":"Akiyama","year":"2025","journal-title":"Br J Dermatol"},{"issue":"4","key":"doi260045r5","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/bjd\/ljaf123","article-title":"Syndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy.","volume":"193","author":"Paller","year":"2025","journal-title":"Br J Dermatol"},{"issue":"9","key":"doi260045r6","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1016\/j.arcped.2005.04.087","article-title":"[Netherton syndrome: a type of infantile erythroderma with failure to thrive, immune deficiency, rickets: report of 3 cases].","volume":"12","author":"Andr\u00e9","year":"2005","journal-title":"Arch Pediatr"},{"issue":"4","key":"doi260045r7","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1159\/000084755","article-title":"Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5.","volume":"210","author":"Geyer","year":"2005","journal-title":"Dermatology"},{"issue":"5","key":"doi260045r8","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.ajhg.2019.09.021","article-title":"Recessive mutations in AP1B1 cause ichthyosis, deafness, and photophobia.","volume":"105","author":"Boyden","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"2","key":"doi260045r9","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/00005176-200402000-00012","article-title":"Nutritional status and gastrointestinal structure and function in children with ichthyosis and growth failure.","volume":"38","author":"Fowler","year":"2004","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"7","key":"doi260045r10","first-page":"829","article-title":"Failure to thrive: an update.","volume":"83","author":"Cole","year":"2011","journal-title":"Am Fam Physician"},{"issue":"3","key":"doi260045r11","doi-asserted-by":"publisher","first-page":"215","DOI":"10.4103\/0022-3859.33872","article-title":"Vitamin D deficiency rickets with lamellar ichthyosis.","volume":"53","author":"Sathish Kumar","year":"2007","journal-title":"J Postgrad Med"},{"issue":"1","key":"doi260045r12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jaad.2020.06.064","article-title":"Malnutrition in children with ichthyosis: recommendations for monitoring from a multidisciplinary clinic experience.","volume":"85","author":"Rodr\u00edguez-Manch\u00f3n","year":"2021","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"doi260045r13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1529-8019.2012.01517.x","article-title":"Complications of ichthyosis beyond the skin.","volume":"26","author":"Diaz","year":"2013","journal-title":"Dermatol Ther"},{"issue":"2","key":"doi260045r14","doi-asserted-by":"publisher","first-page":"660","DOI":"10.12669\/pjms.292.3298","article-title":"Lamellar ichthyosis with rickets.","volume":"29","author":"Ali","year":"2013","journal-title":"Pak J Med Sci"},{"issue":"6","key":"doi260045r18","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2165\/11311070-000000000-00000","article-title":"Ichthyosis: clinical manifestations and practical treatment options.","volume":"10","author":"Oji","year":"2009","journal-title":"Am J Clin Dermatol"},{"issue":"1","key":"doi260045r19","first-page":"106","article-title":"Netherton syndrome: a comprehensive literature review of pathogenesis, clinical manifestations, and therapeutic strategies.","volume":"29","author":"Mocarska","year":"2025","journal-title":"J Mother Child"},{"issue":"5","key":"doi260045r20","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1084\/jem.20082242","article-title":"Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome.","volume":"206","author":"Briot","year":"2009","journal-title":"J Exp Med"},{"issue":"2","key":"doi260045r21","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.jaci.2018.03.021","article-title":"Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature.","volume":"143","author":"Malik","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"doi260045r22","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1186\/s12887-023-04222-8","article-title":"Body surface area is a predictor of maturity status in school children and adolescents.","volume":"23","author":"Alvear-Vasquez","year":"2023","journal-title":"BMC Pediatr"},{"issue":"4","key":"doi260045r23","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1046\/j.1523-1747.2000.00103.x","article-title":"Impaired cutaneous permeability barrier function, skin hydration, and sphingomyelinase activity in keratin 10 deficient mice.","volume":"115","author":"Jensen","year":"2000","journal-title":"J Invest Dermatol"},{"issue":"6","key":"doi260045r24","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.jaci.2020.04.022","article-title":"Skin tape proteomics identifies pathways associated with transepidermal water loss and allergen polysensitization in atopic dermatitis.","volume":"146","author":"Goleva","year":"2020","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"doi260045r25","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/ng1743","article-title":"Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris.","volume":"38","author":"Smith","year":"2006","journal-title":"Nat Genet"},{"issue":"6","key":"doi260045r26","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1111\/j.1365-2133.2010.10068.x","article-title":"Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age.","volume":"163","author":"Flohr","year":"2010","journal-title":"Br J Dermatol"},{"issue":"6","key":"doi260045r27","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1210\/jc.2015-4101","article-title":"Steroid sulfatase deficiency and androgen activation before and after puberty.","volume":"101","author":"Idkowiak","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"doi260045r28","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.bbalip.2013.11.009","article-title":"Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis.","volume":"1841","author":"Elias","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"doi260045r29","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ygeno.2005.01.001","article-title":"Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome.","volume":"85","author":"Galliano","year":"2005","journal-title":"Genomics"},{"issue":"11","key":"doi260045r31","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1080\/21678707.2020.1857724","article-title":"Advances in understanding of Netherton syndrome and therapeutic implications.","volume":"8","author":"Petrova","year":"2020","journal-title":"Expert Opin Orphan Drugs"},{"issue":"3","key":"doi260045r32","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.bbalip.2013.08.009","article-title":"The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation.","volume":"1841","author":"Akiyama","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"52","key":"doi260045r33","doi-asserted-by":"publisher","first-page":"36624","DOI":"10.1074\/jbc.M807377200","article-title":"ABCA12 maintains the epidermal lipid permeability barrier by facilitating formation of ceramide linoleic esters.","volume":"283","author":"Zuo","year":"2008","journal-title":"J Biol Chem"},{"issue":"9","key":"doi260045r34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000192","article-title":"A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.","volume":"4","author":"Smyth","year":"2008","journal-title":"PLoS Genet"},{"issue":"3","key":"doi260045r35","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.jaad.2017.10.026","article-title":"The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: immunophenotyping and response to ustekinumab.","volume":"78","author":"Paller","year":"2018","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"doi260045r36","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/bjd\/ljaf308","article-title":"An analysis of preterm birth rates among 500 kindreds with epidermal differentiation disorders.","volume":"193","author":"Echeandia-Francis","year":"2025","journal-title":"Br J Dermatol"},{"key":"doi260045r30","volume-title":"Filaggrin Gene, Chromosome band 9q34.3, SPINK5, ALCAM and Transepidermal Water Loss","author":"Rajput","year":"2024"},{"key":"doi260045r15","unstructured":"US Centers for Disease Control and Prevention. CDC growth charts data files. Accessed March 10th, 2026, https:\/\/www.cdc.gov\/growthcharts\/who-data-files.htm"},{"key":"doi260045r16","unstructured":"US Centers for Disease Control and Prevention. Child growth standards. Accessed March 10th, 2026, https:\/\/www.cdc.gov\/growthcharts\/who-data-files.htm"},{"key":"doi260045r17","doi-asserted-by":"crossref","unstructured":"Hamilton? BE, Martin? JA, Osterman? M. Births: provisional data for 2022. Accessed March 16, 2026. https:\/\/stacks.cdc.gov\/view\/cdc\/127052","DOI":"10.15620\/cdc:116027"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2854275\/jamadermatology_echeandiafrancis_2026_oi_260045_1789155005.89464.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:32:05Z","timestamp":1790782325000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2854275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":36,"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2026.3782","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}