The Buschke-Ollendorff syndrome: a case report of simultaneous osteo-cutaneous malformations in the hand

Abstract

Background: We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised 7 years before because of consecutive skin contracture. Latest radiological examination showed a spotted pattern consistent with osteopoikilosis.

Case presentation: A corrective osteotomy of the thumb was carried out due to the patients discomfort. Facing the simultaneous osteo-cutaneous malformation we postulated a Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome is a rare autosomal-dominant hereditary disorder of connective tissue with typical osteo-cutaneous manifestations. To explore our hypothesis, biopsies were taken from the affected bone lesions and surrounding skin and soft tissue for histological investigation and genetic testing of the LEMD3 gene was performed on blood of the patient. The histology showed typical changes of the bone architecture and a fibrotic collagenous nodule of the skin. The genetic testing on DNA extracted from peripheral blood leucocytes confirmed a heterozygous loss of function mutation in the LEM domain-containing protein 3 (LEMD3) gene coding for the inner nuclear membrane protein MAN1, which causes osteopoikilosis by antagonizing transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signalling.

Conclusions: In atypical cases of simultaneous occurrence of fibrotic skin lesions and a spotted pattern in the X-ray we recommend the genetic screening of the LEMD3 gene. A correct diagnosis of Buschke-Ollendorff syndrome is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease.

Keywords: Buschke–Ollendorff syndrome; Dermatofibrosis lenticularis disseminata; LEMD3; Osteopoikilosis.

Fig. 1

Radial angulation of the thumb and hypertrophic scar of the soft tissue nodule excision 7 years before. The arrow marks the area where the skin and soft tissue biopsy was taken

Fig. 2

Osteopoikilosis (“spotty bone”)

Fig. 3

Medial closing wedge osteotomy of the proximal phalanx. Note the thickened sclerotic cortical bone

Fig. 4

Histological findings in the skin (H&E, 50×): normal epidermis. Intradermal hypocellular collagenous nodule

Fig. 5

Histological findings in the bone (H&E, 200×): area of thickened cortical bone with remodelling and formation of numerous enlarged Havesian canals

Fig. 6

Electropherogram from Sanger sequencing confirming the heterozygous mutation c.1832T>A detected by next generation sequencing in our patient. The mutation in exon 6 of the LEMD3 gene is predicted to result in a premature stop codon at position 611 (p.Leu611*) of the protein (reference sequence LEMD3 according to GenBank NM_014319.4)