Buschke-Ollendorff syndrome associated with hypertrophic scar formation: a possible role for LEMD3 mutation
Authors: A. Korekawa, H. Nakano, Y. Toyomaki, N. Takiyoshi, D. Rokunohe, E. Akasaka, K. Nakajima, D. Sawamura
Journal: British Journal of Dermatology (2011)

Funding sources: none. Conflicts of interest: none declared. Madam, Buschke–Ollendorff syndrome (BOS; OMIM 166700) is a rare autosomal dominant condition characterized by the development of multiple connective tissue naevi in association with osteopoikilosis and occasionally melorheostosis.1 The clinical expression of this syndrome is quite variable; skin and skeletal lesions may arise independently in affected family members.2 BOS results from loss‐of‐function mutations in the LEMD3 gene, which encodes a potent negative regulator of transforming growth factor (TGF)‐β and bone morphogenic protein signalling pathways;1 the pathogenetic role played by LEMD3 defects in BOS is not fully understood. We report a Japanese family with BOS associated with hypertrophic scar (HS) after traumatic injury. A 5‐year‐old boy presented with asymptomatic multiple cutaneous nodules on his trunk. The lesions had gradually increased in number since they were first noticed on his lower back when he was 5 months old. On physical examination, multiple flesh‐coloured round or oval cutaneous plaques were noted on his abdomen (Fig. 1a) and lower back (Fig. 1b). The lesions were asymmetrically distributed and covered by normal‐appearing skin. There were firm, nodular hypertrophic lesions on his left knee (Fig. 1d) and glabella. These lesions were reported to have arisen after traumatic injury. Lesional skin biopsy from the lower back of the proband revealed increased levels of collagen in the dermis extending into the subcutaneous fat (Fig. 1c). Notably, HS formed at the biopsy incision as it healed. Physical examination of the other family members demonstrated that the proband’s father and elder sister had, to a lesser extent, similar skin plaques on their lower backs, presenting as connective tissue naevi, whereas the mother had no significant skin involvement. Hypertrophic skin lesions at sites of injury, reportedly less elevated than ∼10 years before, were seen on the upper left arm of the father (Fig. 1e) and the right knee of the sister. Neither the collagenous naevi nor the HS lesions followed known cutaneous segments such as Blaschko’s lines. X‐rays of the long bones and pelvis revealed osteopoikilosis, which was distributed symmetrically, in the father (Fig. 1f), but not in the proband. In the affected family members, routine laboratory examinations were within normal limits. Based on these findings, we made a diagnosis of BOS associated with HS. Reverse transcription–polymerase chain reaction (RT‐PCR) was performed as follows: the partial cDNA of LEMD3, spanning exons 5–9, was RT‐PCR amplified from total RNA extracted from peripheral blood leucocytes using an RNeasy extraction kit (Qiagen, Hilden, Germany). Reverse transcription with 0·25 μg of total RNA was carried out using the reverse transcriptase ReverTra Ace™ (Toyobo, Osaka, Japan). First‐strand cDNAs were synthesized by incubation for 10 min at 30 °C, 20 min at 42 °C, 5 min at 99 °C, and 5 min at 4 °C. cDNA for exons 5–9 was PCR amplified using the following specific primers: forward 5′‐TTGGAATAAGGTGTGTTGGT‐3′; reverse 5′‐CTCATTAGCAGCAAGGAAGT‐3′.