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DOI: 10.1111/pde.13287
Juvenile elastoma without germline mutations in LEMD3
gene: A case of Buschke-Ollendorff syndrome?
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.
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
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
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.
© 2017 Wiley Periodicals, Inc.
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
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
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
Alessandra Condorelli MD1
Nicolo Musso PhD2
Laura Scuderi MD1
Daniele F. Condorelli MD, PhD2
Vincenza Barresi PhD2
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
Department of Dermatology, Vittorio Emanuele-Policlinic Hospital,
Catania, Italy
Department of Biomedical and Biotechnological Sciences, Section of
Medical Biochemistry, University of Catania, Catania, Italy
Alessandra Condorelli, MD,
Additional Supporting Information may be found online in the supporting information tab for this article.
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