{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:15:53Z","timestamp":1767834953814,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T00:00:00Z","timestamp":1698537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.<\/jats:p>","DOI":"10.3390\/genes14112021","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T12:50:42Z","timestamp":1698670242000},"page":"2021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-4634","authenticated-orcid":false,"given":"Emilian-Gheorghe","family":"Olteanu","sequence":"first","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Pia\u0163a Eftimie Murgu Nr. 2, 300041 Timisoara, Romania"},{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Bataneant","sequence":"additional","affiliation":[{"name":"Discipline of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Department of Oncology and Hematology, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Puiu","sequence":"additional","affiliation":[{"name":"Discipline of Genetics and Center of Genomic Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-4625","authenticated-orcid":false,"given":"Adela","family":"Chirita-Emandi","sequence":"additional","affiliation":[{"name":"Discipline of Genetics and Center of Genomic Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.iac.2014.01.009","article-title":"Molecular defects in mastocytosis: KIT and beyond KIT","volume":"34","author":"Bibi","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18250","DOI":"10.18632\/oncotarget.4213","article-title":"Mastocytosis: A mutated KIT receptor induced myeloproliferative disorder","volume":"6","author":"Chatterjee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1089\/ped.2013.0275","article-title":"Pediatric Mastocytosis: A Review of the Literature","volume":"26","author":"Frieri","year":"2013","journal-title":"Pediatr. Allergy Immunol. Pulmonol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0190-9622(98)70413-X","article-title":"Congenital bullous mastocytosis with myeloproliferative disorder and c-kit mutation","volume":"39","author":"Shah","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1159\/000243808","article-title":"Clinical Aspects of Diffuse Cutaneous Mastocytosis in Children: Two Variants","volume":"219","author":"Heide","year":"2009","journal-title":"Dermatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e338","DOI":"10.1097\/MPH.0000000000001271","article-title":"c-KIT-Positive Fatal Diffuse Cutaneous Mastocytosis with Systemic Manifestations in a Neonate","volume":"41","author":"Chaudhary","year":"2019","journal-title":"J. Pediatr. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/pde.13801","article-title":"Management of a neonate with diffuse cutaneous mastocytosis: Case report and literature review","volume":"36","author":"Jenkinson","year":"2019","journal-title":"Pediatr. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/jid.2012.394","article-title":"A c-kit Mutation in Exon 18 in Familial Mastocytosis","volume":"133","author":"Moritz","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","unstructured":"Andrews, S. (2020, May 05). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1101\/gr.209601.116","article-title":"UMI-tools: Modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy","volume":"27","author":"Smith","year":"2017","journal-title":"Genome Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Freed, D., Aldana, R., Weber, J.A., and Edwards, J.S. (2017). The Sentieon Genomics Tools\u2013A fast and accurate solution to variant calling from next-generation sequence data. bioRxiv.","DOI":"10.1101\/115717"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R.S., Thormann, A., Flicek, P., and Cunningham, F. (2016). The Ensembl Variant Effect Predictor. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0974-4"},{"key":"ref_14","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus rec-ommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Ge-Netics Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1365-2133.1980.tb07663.x","article-title":"Diffuse cutaneous mastocytosis with multiple cutaneous mastocytomas: Report of a case with clinical, histopathological and ultrastructural aspects","volume":"102","author":"Willemze","year":"1980","journal-title":"Br. J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/archderm.1990.01670350092016","article-title":"The Familial Occurrence of Bullous Mastocytosis (Diffuse Cutaneous Mastocytosis)","volume":"126","author":"Oku","year":"1990","journal-title":"Arch. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1046\/j.1525-1470.1999.016005406.4.x","article-title":"Diffuse cutaneous mastocytosis with bullae or bullous mastocytosis: A question of semantics","volume":"16","author":"Sethuraman","year":"1999","journal-title":"Pediatr. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1542\/peds.19.6.1033","article-title":"Mast Cell Leukemia Presenting as Urticaria Pigmentosa: Report of a case","volume":"19","author":"Waters","year":"1957","journal-title":"Pediatrics"},{"key":"ref_19","first-page":"1558","article-title":"A fatal case of purely cutaneous form of diffuse mastocytosis","volume":"2","author":"Yasuda","year":"1962","journal-title":"Proc. XII Int. Cong Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1440-0960.1967.tb01156.x","article-title":"Skin Mastocytosis Presenting as a Neonatal Bullous Eruption","volume":"9","author":"Allison","year":"1967","journal-title":"Australas. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1001\/archderm.1968.01610180034004","article-title":"Mast Cell Disease: A cutaneous variant with multisystem involvement","volume":"98","author":"Burgoon","year":"1968","journal-title":"Arch. Dermatol."},{"key":"ref_22","first-page":"16","article-title":"Diffuse cutaneous mastocytosis in mother and daughter","volume":"69","author":"Klaber","year":"1976","journal-title":"Proc. R. Soc. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2340\/0001555559541543","article-title":"Diffuse cutaneous mastocytosis: A report of neonatal onset","volume":"59","author":"Harrison","year":"1979","journal-title":"Acta Derm.-Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1046\/j.1365-2230.1999.00397.x","article-title":"Diffuse cutaneous mastocytosis responding to cyproheptadine","volume":"24","author":"Enomoto","year":"1999","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1440-0960.2001.00466.x","article-title":"Presentation of cutaneous mastocytosis in 173 children","volume":"42","author":"Hannaford","year":"2001","journal-title":"Australas. J. Dermatol."},{"key":"ref_26","first-page":"176","article-title":"Systemic mastocytosis in childhood: Report of 3 cases","volume":"78","author":"Fernandes","year":"2002","journal-title":"J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jpeds.2003.11.015","article-title":"Congenital cutaneous mastocytosis","volume":"145","author":"Mann","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000089026","article-title":"Neonatal Mastocytosis with Pachydermic Bullous Skin without c-Kit 816 Mutation","volume":"212","author":"Walker","year":"2005","journal-title":"Dermatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/j.1365-4632.2009.03439.x","article-title":"Diffuse cutaneous mastocytosis in fraternal twins","volume":"48","author":"Duckworth","year":"2009","journal-title":"Int. J. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/j.1525-1470.2010.01212.x","article-title":"Neonatal Onset Diffuse Cutaneous Mastocytosis: A Case Report and Review of the Literature","volume":"28","author":"Koga","year":"2010","journal-title":"Pediatr. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1111\/j.1468-3083.2011.04350.x","article-title":"Diffuse cutaneous mastocytosis: Analysis of 10 cases and a brief review of the literature","volume":"26","author":"Lange","year":"2011","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_32","first-page":"7","article-title":"Diffuse cutaneous mastocytosis: Report of a severe case with fatal outcome","volume":"17","author":"Ghiasi","year":"2011","journal-title":"Dermatol. Online J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.14734\/kjp.2014.25.2.105","article-title":"A Case of Diffuse Cutaneous Mastocytosis in a Newborn","volume":"25","author":"Park","year":"2014","journal-title":"Korean J. Perinatol."},{"key":"ref_34","first-page":"286","article-title":"Diffuse cutaneous mastocytosis. Presentation of 3 cases and therapeutic management review","volume":"5","author":"Folch","year":"2016","journal-title":"An. Pediatr. A (Engl. Ed.)"},{"key":"ref_35","first-page":"12","article-title":"Congenital Mastocytosis: Case Report and Review of the Literature","volume":"12","author":"Turnbull","year":"2020","journal-title":"Cureus"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1046\/j.1468-3083.2000.00018.x","article-title":"Familial mastocytosis associated with neurosensory deafness","volume":"14","author":"Trevisan","year":"2000","journal-title":"J. Eur. Acad. Dermatol. Venereol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/11\/2021\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:51Z","timestamp":1760130831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/11\/2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,29]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["genes14112021"],"URL":"https:\/\/doi.org\/10.3390\/genes14112021","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,29]]}}}