Linear scleroderma and melorheostosis: Case presentation and literature review

Alvarez, M. J. Moreno; Lázaro, María Alicia; Espada, Graciella; Barcelo, H; Cocco, Antonio

doi:10.1007/bf02230364

Cited by 21 publications

(13 citation statements)

References 10 publications

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“…Soft tissue abnormalities overlying MEL (59) can also include skin changes; (17) scleroderma-like patches over MEL have been documented since 1936. (5–11) Furthermore, linear scleroderma with MEL in OPK/BOS and resembling OPK has been described. (25–27) In 2003, Tinschert et al (34) reported an occurrence of extensive sebaceous nevus (LEN of the scalp) accompanying MEL and hypothesized non-allelic didymosis (i.e., twin spotting) as the genetic basis.…”

Section: V) Discussionmentioning

confidence: 99%

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Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS

Whyte

Griffith

Trani

et al. 2017

Bone

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Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3 gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient’s mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of him and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using five algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS, perhaps facilitated by germline LEMD3 haploinsufficiency, causing his MEL.

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Section: V) Discussionmentioning

confidence: 99%

“…(2–4) Not infrequently, scleroderma-like skin change (SLS), (5–11) nevi of various types, (12) or vascular abnormalities (13) overlie MEL bone. Sometimes MEL becomes malignant.…”

Section: Ii) Introductionmentioning

confidence: 99%

Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS

Whyte

Griffith

Trani

et al. 2017

Bone

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“…Although a benign dysplasia, the osseous changes can cause morbidity. Skin and subcutaneous tissue involvement can result in fibrosis and joint contractures leading to deformity and limb-length discrepancy (3,(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Melorheostosis and a review of the literature in China

Zhang

Dai

Yang

et al. 2013

Intractable Rare Dis Res

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“…In some cases the soft tissues overlying the bones may show sclerosis [92,93]. The cutaneous manifestations may include scleroderma-like asymmetrical bands of sclerosis, and fibrotic contractures.…”

Section: Other Hereditary Scleroderma-like Dis-ordersmentioning

confidence: 96%

Clinical Features of Scleroderma-Like Disorders: A Challenge for the Rheumatologist

Czirják¹,

Varjú

2006

CRR

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Systemic sclerosis (SSc) is characterized by vascular abnormalities, fibrosis, inflammatory changes, and late stage atrophy/obliterative vasculopathy. Localized scleroderma forms show a longitudinal or circumscribed skin involvement. In scleroderma-like disorders the distribution/characteristics of skin involvement seem to be "atypical" as compared to classic SSc, and the acral skin involvement is usually missing. Exposure to certain chemicals or drugs may also suggest the presence of a scleroderma-like disease. Lack of Raynaud's phenomenon, scleroderma-specific antinuclear antibodies, scleroderma capillary pattern on nailfold capillaroscopy, and typical internal organ manifestations may also indicate the presence of a scleroderma-like disorder. For differential diagnosis skin biopsy is almost always required.Scleroderma-like disorders include diseases with mucin deposition (scleromyxedema, scleredema, etc.). Some disorders show papular-nodular skin changes with or without dermal deposition of materials (amyloid, mucin deposition; fibroblastic rheumatism, etc.). Diseases with monoclonal gammopathy (scleromyxedema, POEMS syndrome, myeloma with scleroderma-like skin changes) also belong to the large group of scleroderma-like diseases. Some disorders are characterized by eosinophilia (diffuse fasciitis with eosinophilia, eosinophilia-myalgia syndrome, toxic oil syndrome), metabolic/biochemical abnormalities (IDDM, nephrogenic fibrosing dermopathy), and endocrine abnormalities (POEMS syndrome, hypo/hyperthyroidism with mucin deposition, diabetes). Chronic graft-versus host disease (cGVHD) may also show scleroderma-like skin changes.Scleroderma-like disorders can be induced by drugs or chemicals (eosinophilia-myalgia syndrome, toxic oil syndrome, vinyl-chloride disease; cytostatic/appetite suppressant, etc), and also by physical injury (trauma, vibration stress, radiation injury). Inherited progeroid syndromes with early ageing (Werner's syndrome, etc.), and a large heterogeneous group of hereditary disorders with either skin thickening (porphyria, phenylketonuria) or skin atrophy/tightening (restrictive dermopathy, scleroatrophic and keratotic dermatosis of the limbs, etc.) should also be taken in consideration in the differential diagnosis of scleroderma-like disorders. These categories are not mutually exclusive, because the remarkably different scleroderma-like diseases show overlapping features.

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Linear scleroderma and melorheostosis: Case presentation and literature review

Abstract: The case of a 9 year-old male patient with linear scleroderma and melorheostosis of the iliac bone is described. Radiological findings suggestive of osteopoikilosis were found in carpal and tarsal bones. A review of the literature on this unusual disease association is made.

Cited by 21 publications

References 10 publications

Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS

Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS

Melorheostosis and a review of the literature in China

Clinical Features of Scleroderma-Like Disorders: A Challenge for the Rheumatologist

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