AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Buschke-Ollendorff syndrome is a rare hereditary disorder of connective tissue. It is inherited as a pleiotropic autosomal dominant trait with incomplete penetrance. This condition was described for the first in 1902 and was termed "scleroderma adultorum" by Abraham Buschke. Then, Heinrich Ernst Albers-Schönberg described this syndrome in 1915. Finally, Buschke and Helene Ollendorff Curth described it in 1928 in a 41-year-old woman. Buschke-Ollendorff syndrome is considered to be a hamartoma, an association of osteopoikilosis and connective tissue nevi.^{1, 2, 3, 4, 5}

Pathophysiology

In the presence of 10% calf serum, cultured fibroblasts of patients with Buschke-Ollendorff syndrome produce 2-8 times more tropoelastin than fibroblasts of healthy individuals. Elastin production is higher in involved and uninvolved skin.^{6, 7, 8} Elevated elastin mRNA levels suggest that Buschke-Ollendorff syndrome may result from abnormal regulation of extracellular matrix, leading to increased levels of elastin mRNA and increased accumulation of elastin in the dermis [10]. Noteworthy is that heterozygous loss-of-function mutation in the LEMD3 (LEM domain containing 3) gene (locus 12q14) for an inner nuclear membrane protein has been identified in patients with osteopoikilosis with or without Buschke-Ollendorff syndrome.^{5, 9, 10, 11}

Frequency

International

Buschke-Ollendorff syndrome is rare (1 case per 20,000 population).⁵

Mortality/Morbidity

The cause of mortality may be malignant transformation of bone densities into osteosarcoma, chondrosarcoma, and giant cell tumor. The otosclerosis with hearing impairment, stenosis of the aortae, and diabetes frequently found in this syndrome make the patient's condition serious.^{4, 12, 13}

Race

No racial predilection is reported for Buschke-Ollendorff syndrome.⁵

Sex

The incidence is equal for males and females.⁵

Age

Skin lesions are visible in neonates just after birth. Other factors of the syndrome are revealed with time.⁴

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

History findings are as follows^{1, 4, 5, 14, 15}:

• The coexistence of cutaneous lesions, such as disseminated lenticular dermatofibrosis, and skeletal changes, such as osteopoikilosis, characterize Buschke-Ollendorff syndrome.
• Cutaneous lesions appear in childhood, often in the first year of life. They may be observed in the fetus. Rarely, they may occur in adulthood.
• They are usually located on the trunk and the proximal extremities, and the skin folds are often involved.
• The lesions are painless, nonpruritic, and enlarge with the growth of the child.

Physical

Physical findings are as follows^{1, 3, 4, 5, 14, 15, 16, 17, 18, 19, 20, 21}:

• Buschke-Ollendorff syndrome is an association of disseminated lenticular dermatofibrosis and osteopoikilosis. The dermal lesions are composed of collagen and elastin fibers and, in some instances, mucopolysaccharides. The cutaneous lesions are usually localized on the trunk; in the sacrolumbar region; and, symmetrically, on the extremities. Occasionally, the lesions may be found on the head. They present with slightly elevated and flattened yellowish papules and nodules grouped together forming plaques several centimeters in diameter. The plaques are of irregular shape and sharply demarcated. They are numerous, painless, nonpruritic, and develop over several years. In some individuals, only dermal or osteopoikilosis manifestations may be present.
• Other findings in Buschke-Ollendorff syndrome include nasolacrimal duct obstruction, amblyopia, strabismus, benign lymphoid hyperplasia, hypopigmentation, and short stature.
• The bones demonstrate osteopoikilosis in the stratum spongiosum of the epiphysis and the metaphysis of the long bones, especially in the fingers, the ulna, and the radius. Focal bone densities are often present in the carpal bones, the metacarpal bones, and the phalanges. They also occur in the lumbosacral spine. Each focal area of density may measure from 1-16 mm in length. Other forms of osteosclerosis, including osteopathia striata, melorheostosis, and mixed sclerosis bone dystrophy, may be present.
• Congenital spinal stenosis, disc herniation, clubfoot deformity, and nerve root compression may be present.
• Otosclerosis with or without hearing loss may occur. It is caused by bone resorption and redeposition, and it may be clinically asymptomatic; however, otosclerosis is a rare phenomenon in patients with Buschke-Ollendorff syndrome.

Causes

The syndrome is inherited as an autosomal dominant variant with incomplete penetrance.^{1, 4, 5}

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Disseminated nevus anelasticus
The differential diagnosis of osteopoikilosis includes osteopathia striata, melorheostosis, sclerotic bone metastases, tuberous sclerosis (see Tuberous Sclerosis), osteomas (Osteoma Cutis), and mastocytosis (Mastocytosis).

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

Perform a histologic examination of the dermal lesions and screen for diabetes.^{4, 22}

Imaging Studies

Consider the following with regard to image studies^{1, 2, 4, 5, 21, 23}:

• In Buschke-Ollendorff syndrome, the radiographic appearance of osteopoikilosis is diagnostic. Bone densities are often present in the fingers, the carpal and metacarpal bones, the lumbosacral spine, and the tibial and radial bones. They are sclerotic circular or ovoid lesions symmetrically distributed in a periarticular location, and they may be 1-16 mm in diameter. Lesions can increase or decrease in size and number or even disappear in serial radiographs. The bone densities are caused by condensations of the spongiosa.
• Other sclerosing dysplasias, including osteopathia striata, melorheostosis, and focal sclerosis, can be seen. When osteopoikilosis is seen in combination with these sclerosing dysplasias, the term mixed sclerosing bone dystrophy is used.
• Lesions do not have increased bone radiotracer uptake.
• T1-weighted MRI reveals multiple, well-circumscribed, low-signal foci usually in a symmetric distribution. The differential diagnosis includes blastic metastases, tuberous sclerosis, and mastocytosis. However, symmetry and uniform size of the lesions would be most suggestive of osteopoikilosis.

Other Tests

• Genetic tests
• Genomic Medicine Resource Center

Histologic Findings

Histopathologic examination reveals numerous thickened collagen fibers in the dermis. Orcein stain of the reticular layer of the dermis reveals numerous elastic fibers with various diameters. These fibers are frequently fragmented, and, in some places, they create a net of bundles. Weigert stain of the reticular dermis also reveals numerous elastic fibers with different diameters.⁷

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

Diabetes, if present, requires appropriate specialty care.

Surgical Care

• Surgical excision of the dermal lesions is indicated only for cosmetic reasons.
• In some patients, surgical treatment of deafness is possible.
• Surgical treatment of associated conditions, such as stenosis of the aortae, should be performed as appropriate.

Consultations

• Laryngologic examination with audiogram
• Ophthalmologic examination with ophthalmoscopy
• General physical examination with ECG

Activity

Osteopoikilosis is asymptomatic; however, 15-20% of patients experience pain and joint effusions. Usually, no special restrictions in activity are required.⁵

FOLLOW-UP

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Complications

Complications can include the following^{4, 12, 13}:

• Bone malignancy
• • Osteosarcoma
  • Chondrosarcoma
  • Giant cell tumor
• Hearing impairment
• Stenosis of the aortae
• Diabetes

Prognosis

When visceral or metabolic changes (diabetes) are present, the prognosis can be serious.

Patient Education

The patient and/or the patient's family should be educated concerning potential complications.

MISCELLANEOUS

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to diagnose potential associated features, such as hearing impairment, stenosis of the aortae, and diabetes, is a pitfall.

ACKNOWLEDGMENTS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Mieczyslawa Miklasewska, MD, and Grazyna Szybejko-Machaj, MD, to the development and writing of this article.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Plaque of grouped papular eruptions on the thigh.
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Media file 2:  Hematoxylin and eosin stain shows the histopathologic features of the skin lesions.
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Media file 3:  Small longitudinal lesions of increased bone density in the proximal epiphysis of the left tibial bone and in the distal epiphysis of the right tibial bone.
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Media type:  X-RAY

Media file 4:  Orcein stain of elastic fibers shows the histopathologic features of the skin lesions.
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Media type:  Photo

Media file 5:  Weigert stain of the elastic fibers shows the histopathologic features of the skin lesions.
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Media type:  Photo

Media file 6:  Plaque of grouped papules on the abdominal coat.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

1. Benli IT, Akalin S, Boysan E, Mumcu EF, Kis M, Türkoglu D. Epidemiological, clinical and radiological aspects of osteopoikilosis. J Bone Joint Surg Br. Jul 1992;74(4):504-6. [Medline].
2. Crivellato E. Disseminated nevus anelasticus. Int J Dermatol. Apr 1986;25(3):171-3. [Medline].
3. Dahan S, Bonafe JL, Laroche M, et al. [Iconography of Buschke Ollendorff syndrome: x ray computed tomography and nuclear magnetic resonance of osteopoikilosis]. Ann Dermatol Venereol. 1989;116(3):225-30. [Medline].
4. Lin F, Morrison JM, Wu W, Worman HJ. MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum Mol Genet. Feb 1 2005;14(3):437-45. [Medline].
5. de la Salmonière P, Janier M, Chemlal K, Lazareth I, Carlotti A, Charasson I, et al. [Buschke-Ollendorff syndrome]. Ann Dermatol Venereol. 1994;121(10):718-20. [Medline].
6. Ehrig T, Cockerell CJ. Buschke-Ollendorff syndrome: report of a case and interpretation of the clinical phenotype as a type 2 segmental manifestation of an autosomal dominant skin disease. J Am Acad Dermatol. Dec 2003;49(6):1163-6. [Medline].
7. Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PC, Costa T, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. Nov 2004;36(11):1213-8. [Medline].
8. Trattner A, David M, Rothem A, Ben-David E, Sandbank M. Buschke-Ollendorff syndrome of the scalp: histologic and ultrastructural findings. J Am Acad Dermatol. May 1991;24(5 Pt 2):822-4. [Medline].
9. Ben-Asher E, Zelzer E, Lancet D. LEMD3: the gene responsible for bone density disorders (osteopoikilosis). Isr Med Assoc J. Apr 2005;7(4):273-4. [Medline].
10. Grimer RJ, Davies AM, Starkie CM, Sneath RS. [Chondrosarcoma in a patient with osteopoikilosis. Apropos of a case]. Rev Chir Orthop Reparatrice Appar Mot. 1989;75(3):188-90. [Medline].
11. Lagier R, Mbakop A, Bigler A. Osteopoikilosis: a radiological and pathological study. Skeletal Radiol. 1984;11(3):161-8. [Medline].
12. Ayling RM, Evans PE. Giant cell tumor in a patient with osteopoikilosis. Acta Orthop Scand. Feb 1988;59(1):74-6. [Medline].
13. Giro MG, Duvic M, Smith LT, Kennedy R, Rapini R, Arnett FC, et al. Buschke-Ollendorff syndrome associated with elevated elastin production by affected skin fibroblasts in culture. J Invest Dermatol. Aug 1992;99(2):129-37. [Medline].
14. Morrison JG, Jones EW, MacDonald DM. Juvenile elastoma and osteopoikilosis (the Buschke--Ollendorff syndrome). Br J Dermatol. Oct 1977;97(4):417-22. [Medline].
15. Schorr WF, Optiz JM, Reyes CN. The connective tissue nevus-osteopoikilosis syndrome. Arch Dermatol. Aug 1972;106(2):208-14. [Medline].
16. Al Attia HM, Sherif AM. Buschke-Ollendorff syndrome in a grande multipara: a case report and short review of the literature. Clin Rheumatol. 1998;17(2):172-5. [Medline].
17. Atherton DJ, Wells RS. Juvenile elastoma and osteopoikilosis (the Buschke-Ollendorf syndrome). Clin Exp Dermatol. Jan 1982;7(1):109-13. [Medline].
18. Cantatore FP, Carrozzo M, Loperfido MC. Mixed sclerosing bone dystrophy with features resembling osteopoikilosis and osteopathia striata. Clin Rheumatol. Jun 1991;10(2):191-5. [Medline].
19. Miklaszewska M, Szybejko-Machaj G, Szepietowski J. [Buschke-Ollendorf syndrome - case report with a literature review.]. Dermatol Klin Zabieg. 1999;2:85-9.
20. Schnur RE, Grace K, Herzberg A. Buschke-Ollendorff syndrome, otosclerosis, and congenital spinal stenosis. Pediatr Dermatol. Mar 1994;11(1):31-4. [Medline].
21. Woodrow SL, Pope FM, Handfield-Jones SE. The Buschke-Ollendorff syndrome presenting as familial elastic tissue naevi. Br J Dermatol. Apr 2001;144(4):890-3. [Medline].
22. Smith AD, Waisman M. Connective tissue nevi; familial occurrence and association with osteopoikilosis. Arch Dermatol. Feb 1960;81:249-52. [Medline].
23. Holbrook KA, Byers PH. Structural abnormalities in the dermal collagen and elastic matrix from the skin of patients with inherited connective tissue disorders. J Invest Dermatol. Jul 1982;79 Suppl 1:7s-16s. [Medline].
24. Hassikou H, Tabache F, Safi S, Baaj M, Hadri L. Buschke-Ollendorff syndrome. Joint Bone Spine. Mar 2008;75(2):212-4. [Medline].
25. Uitto J, Santa Cruz DJ, Starcher BC, Whyte MP, Murphy WA. Biochemical and ultrastructural demonstration of elastin accumulation in the skin lesions of the Buschke-Ollendorff syndrome. J Invest Dermatol. Apr 1981;76(4):284-7. [Medline].

Article Last Updated: Jul 2, 2008