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


METHODS
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.
Department of Hand Plastic and Reconstructive Surgery, Cantonal Hospital, St. Gallen, Switzerland. michael.brodbeck@kssg.ch.
Michael
M
Brodbeck
Department of Hand Plastic and Reconstructive Surgery, Cantonal Hospital, St. Gallen, Switzerland.
Q
Q
Yousif
Department of Pathology, Cantonal Hospital, St. Gallen, Switzerland.
P A
PA
Diener
Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
M
M
Zweier
Department of Hand Plastic and Reconstructive Surgery, Cantonal Hospital, St. Gallen, Switzerland.
J
J
Gruenert
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010023:Osteopoikilosis / Q000235:genetics / Q000473:pathology*; D012689:Sequence Homology, Nucleic Acid; D012868:Skin Abnormalities; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000473:pathology*; D013933:Thumb / Q000002:abnormalities* / Q000601:surgery; D055815:Young Adult
D004268:DNA-Binding Proteins; C405329:LEMD3 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins
Buschke–Ollendorff syndrome; Dermatofibrosis lenticularis disseminata; LEMD3; Osteopoikilosis