DOI: 10.1111/pde.13287 Pediatric Dermatology BRIEF REPORT Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke-Ollendorff syndrome? Abstract We report the case of a 6-year-old Caucasian girl with clinical and BOS.3 No bony lesions were found in the radiographs of the patient’s histopathologic features of Buschke-Ollendorff syndrome. Histologic arms, legs, or pelvis. examination of skin lesions showed thick, curly, elastic fibers in the Because heterozygous loss-of-function mutations in the LEMD3 derma. Bone lesions compatible with Buschke-Ollendorff syndrome gene have been identified in individuals with BOS,2 LEMD3 was were found in the girl’s mother. Mutations in LEMD3 are pathogenic analyzed using multiplex polymerase chain reaction and amplicon for Buschke-Ollendorff syndrome. Analysis of all exons and exon- next-generation sequencing (NGS; Ion PGM System, Thermo Fisher intron junctions of LEMD3 did not reveal any germline mutations. Scientific, Waltham, MA) in the patient and her mother. Primers for amplicon generation from LEMD3 (GenBank accession number NM_014319.4; 13 exons; 40 amplicons) have been designed to cover all exons and the exon-intron regions. 1 | INTRODUCTION Sequencing of the patient’s blood DNA revealed one variant in the LEMD3 gene (Supplementary Table S1). Such a variant can be A 6-year-old Caucasian girl was seen for evaluation of skin-colored considered a genetic polymorphism because the minor allele papules, 0.5 to 1 cm in diameter, in an asymmetric distribution on the frequency is 0.418. All the genetic variants detected in the mother’s trunk and upper limbs (Figure 1A-B). Histologic examination of a DNA were compatible with the patient’s variants and were non- biopsy revealed thick, curly, elastic fibers in the deep dermis (Fig- pathogenic genetic polymorphisms. ure 1C) compatible with Buschke-Ollendorff syndrome (BOS), an autosomal dominant disease characterized by connective tissue nevi and osteopoikilosis.1,2 Family history was negative for similar skin 2 | DISCUSSION lesions. Radiographic studies of the patient’s mother’s limbs, hands, feet, and pelvis found a small sclerotic oval area (Figure 1D) in the We present the case of a 6-year-old girl with skin lesions with clini- mother’s femur. Similar lesions have been reported in association with cal and histologic features of BOS but without detected pathogenic (B) (A) (C) (D) F I G U R E 1 (A, B) Skin-colored papules of the chest, upper limbs, and back with an asymmetric distribution. (C) Histologic examination of the deep dermis. Orcein staining (920). (D) Femur X-ray examination of patient’s mother. Posterioranterior projection. The red arrow indicates the sclerotic area next to the greater trochanteric region Pediatric Dermatology. 2017;1–2. wileyonlinelibrary.com/journal/pde © 2017 Wiley Periodicals, Inc. | 1 2 | Pediatric Dermatology BRIEF REPORT mutations in the LEMD3 gene. Yadegari and colleagues reported a Department of Dermatology, Vittorio Emanuele-Policlinic Hospital, family with BOS without germline mutations in LEMD3.4 Although it Catania, Italy. is possible that our patient had a sporadic juvenile elastoma, given Email: firstname.lastname@example.org the number of lesions and the known extreme variability of expression in BOS,5 as well as her young age, we suspect that the patient Alessandra Condorelli and Nicolo Musso contributed equally to this work. and her mother have BOS despite the failure to find pathogenic changes in LEMD3. LEMD3 is an integral protein of the inner nuclear membrane that binds the SMAD proteins antagonizing transforming growth factorbeta (TGF-ß) and bone morphogenetic protein (BMP) pathways. Haploinsufficiency of LEMD3 results in enhanced TGF-ß and BMP signaling, with increased production of elastic and collagen fibers in the dermis and excessive bone tissue. The absence of LEMD3 pathogenic variants in our case suggest that further research is needed to identify other genes involved in the pathogenesis of BOS or juvenile elastoma. Alessandra Condorelli MD1 Nicolo Musso PhD2 Laura Scuderi MD1 Daniele F. Condorelli MD, PhD2 Vincenza Barresi PhD2 REFERENCES 1. Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004;36:1213-1218. 2. Zhang Y, Castori M, Ferranti G, Paradisi M, Wordsworth BP. Novel and recurrent germline LEMD3 mutations causing Buschke-Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis. Clin Genet. 2009;75:556-561. 3. Lygdas P, Ballas EG, Stathopoulos IP, Theologis T, Pistevos K, Pasparakis D. Buschke-Ollendorff syndrome accidentally diagnosed after a left ankle sprain. J Musculoskelet Neuronal Interact. 2014;14:144-147. 4. Yadegari M, Whyte MP, Mumm S, et al. Buschke-Ollendorff syndrome: absence of LEMD3 mutation in an affected family. Arch Dermatol. 2010;146:63-68. 5. Foo CC, Kumarasinghe SP. Juvenile elastoma: a forme fruste of the Buschke-Ollendorff syndrome? Australas J Dermatol. 2005;46:250-252. Rocco De Pasquale MD1 1 Department of Dermatology, Vittorio Emanuele-Policlinic Hospital, Catania, Italy 2 Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Catania, Italy Correspondence Alessandra Condorelli, MD, SUPPORTING INFORMATION Additional Supporting Information may be found online in the supporting information tab for this article.