Dermatology: Practical and Conceptual Image Letter | Dermatol Pract Concept. 2023;13(4):e2023225 1 A Rare Genetic Disorder: Keutel Syndrome with Dermatologic Manifestation Didem Kazan1, Hatice Eloglu1, Rebiay Kiran1 1 Department of Dermatology and Venerology, Kocaeli University, Kocaeli, Turkey Citation: Kazan D, Eloglu H, Kiran R. A Rare Genetic Disorder: Keutel Syndrome with Dermatologic Manifestation. Dermatol Pract Concept. 2023;13(4):e2023225. DOI: https://doi.org/10.5826/dpc.1304a225 Accepted: April 7, 2023; Published: October 2023 Copyright: ©2023 Kazan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Didem Kazan, Department of Dermatology and Venerology, Kocaeli University. Tel : +902623037575 E-mail: didem.senses_343@hotmail.com Case Presentation A 26-year-old female presented with erythematous atrophic irregularly bordered depressed patches on both sides of the neck that gradually developed over the 5 months. She was previously diagnosed with contact dermatitis, and treated with two weeks of topical hydrocortisone cream without any improvement. She also had stridor and recurrent respiratory infections since her childhood, hear-loss, and nose augmen- tation operation 6 years ago. Dermatological examination revealed erythematous atrophic patches on both sides of the neck, and laxity on both sides of the trunk (Figure 1, A-C). In addition, frontal bossing, maxillary hypoplasia, hypoplastic small nose with a broad, depressed nasal bridge and hypo- plastic nostrils, short philtrum, prominent eyes, and dental malocclusion were observed. Her parents were first-degree cousins. On presentation to our clinic, punch biopsy from multiple skin lesions revealed elastin fragmentation and loss on the superficial dermis (Figure 1 D). Based on these find- ings our patient was diagnosed with Keutel syndrome with skin manifestation. She was treated with barrier cream and sunscreen. Teaching Point Keutel Syndrome (KS) is a rare autosomal recessive he- reditary genetic disorder with an estimated prevalence of 1:1000000 [1]. It is associated with loss-of-function muta- tions in the gene coding for the matrix Gla protein (MGP). Abnormal calcification of cartilaginous tissues resulting in malformations of skeletal tissues (eg, midface hypoplasia ), respiratory defects (eg, tracheobronchial cartilage calcifica- tion ), and cardiovascular defects (eg, arterial calcification). Khosroshahi et al reported long-term follow-up results of 4 patients with KS [2]. All patients developed erythematous atrophic skin lesions after 30 years of age. The pathogenesis of skin findings in KS is not fully understood. It is thought to develop because of the destruction of elastic fibers in the papillary dermis due to progressive abnormal calcification [1,2]. However, we think that further studies will show the reasons why especially the elastic fibers of the papillary der- mis are affected and that these findings develop after the age of 30. Although systemic treatment with vitamin K supple- ments has been tried previously, curative treatment has not been available [3]. However, multidisciplinary follow-up for 2 Image Letter | Dermatol Pract Concept. 2023;13(4):e2023225 systemic involvement is vital [1,2]. Dermatologists play a key role also in the diagnosis of genetic diseases. Keutel syn- drome is a rare genetic disorder but should be kept in mind, especially in the presence of a phenotype suggestive of a ge- netic syndrome and erythematous atrophic patches located on the neck and upper body. References 1. Cancela ML, Laizé V, Conceição N, Kempf H, Murshed M. Keutel Syndrome, a review of 50 years of literature. Front Cell Dev Biol. 2021;9:642136. DOI: 10.3389/fcell.2021.642136. PMID: 33996798. PMCID: PMC8117146. 2. Khosroshahi HE, Sahin SC, Akyuz Y, Ede H. Long term fol- low-up of four patients with Keutel syndrome. Am J Med Genet A. 2014;164A(11):2849-2856. DOI: 10.1002/ajmg.a.36699. PMID: 25123378. 3. Cranenburg EC, VAN Spaendonck-Zwarts KY, Bonafe L, Mittaz Crettol L, Rödiger LA, Dikkers FG, VAN Essen AJ, Superti-Furga A, Alexandrakis E, Vermeer C, Schurgers LJ, Laverman GD. Cir- culating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome. J Thromb Haemost. 2011 Jun;9(6):1225-35. doi: 10.1111/j.1538-7836.2011.04263.x. PMID: 21435166. Figure 1. (A, B) Erythematous atrophic patches on the both sides of neck. (C) Prominent laxity on the trunk, (D) Fragmantation and loss of elastin on the dermis (H&E, X100).