Acta Dermato-Venerelogica Issue No 7, 2017 97-7CompleteContent | Page 24

858 SHORT COMMUNICATION Heterozygous PDGFRB Mutation in a Three-generation Family with Autosomal Dominant Infantile Myofibromatosis Clémence LEPELLETIER 1,2 , Yasser AL-SARRAJ 3 , Christine BODEMER 1,2 , Hibbah SHAATH 3 , Sylvie FRAITAG 2,4 , Marios KAMBOURIS 3,5,6 , Dominique HAMEL-TEILLAC 1 , Hatem EL-SHANTI 3,7,8 and Smail HADJ-RABIA 1,2 Departments of 1 Dermatology and 4 Pathology, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, FR-75015 Paris, 2 Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), INSERM U1163, Université Paris Descartes – Sorbonne Paris Cité, Institut Imagine, Hôpital Universitaire Necker-Enfants Malades, Paris, France, 3 Qatar Biomedical Research Institute, Medical Genetics Center, 5 Pathology – Genetics, Sidra Medical and Research Center, Doha, Qatar, 6 Yale University School of Medicine, Genetics, New Haven CT, 7 University of Iowa, Carver College of Medicine, Iowa City, IA, USA, and 8 University of Jordan, School of Medicine, Amman, Jordan. E-mail:[email protected] Accepted Apr 6, 2017; Epub ahead of print Apr 17, 2017 Infantile myofibromatosis (IM; MIM#228550) is a rare disorder of myofibroblastic proliferation and is one of the most common causes of benign fibrous tumour of infancy (1). IM is categorized into solitary, multicentric and generalized forms, with solitary IM be- ing the most common. While solitary IM is characterized by the presence of a single cu- taneous nodule, multicentric IM involves t he skin, subcutaneous tissues, muscles and bones. Both forms of IM regress spontaneously during childhood. Generalized IM is characterized by visceral involvement, and may have a poor outcome. Although IM is mainly sporadic, 30 families suggestive of autosomal dominant (AD) or autosomal recessive (AR) inheritance have been reported. Recently, heterozygous mutations in PDGFRB and NOTCH3 have been reported in 13 families with AD IM (2, 3). We report here, a 3-generation family with multicentric AD IM and a novel PDGFRB mutation (c.1679C>T; p.P560L). history of IM. Variants in NOTCH3 and PTPRG were excluded by whole-exome sequencing. https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2671 1 CASE REPORT A male patient (III-2) was referred at birth due to the presence of 4 firm, flesh-coloured subcutaneous nodu- les; 2 on the scalp, 1 on the left shoulder and 1 on the back (Fig. 1a–c). Histopathology of the dorsal nodule biopsy was consistent with a diagnosis of IM (Fig. 1d, e). Systemic monitoring showed multiple skeletal in- volvement and a 3-cm nodule of the left psoas muscle, partially infiltrating the spinal canal. No visceral lesions were found. Spontaneous, complete and uncomplicated regression occurred during the first 2 years of life. The patient belongs to a French family of Spanish origin. Six of his relatives presented with AD multi- centric IM (Fig. 1a, Table SI 1 ). Of note, individual III-3 had a solitary IM subcutaneous nodule 5 years after complete regression of the neonatal lesions. None of the affected relatives presented with skeletal overgrowth, neurological deterioration or dysmorphic features. After obtaining informed consent, DNA extracted from blood leucocytes was analysed by whole exome sequencing for each patient and relative. Re-sequencing of PDGFRB identified a heterozygous missense mutation in exon 12 (c.1679C>T;p.P560L), which segregates with the disease in the family, and identified individual I-1 as the founder despite no doi: 10.2340/00015555-2671 Acta Derm Venereol 2017; 97: 858–859 Fig. 1. Familial autosomal dominant infantile myofibromatosis (IM): pedigree, clinical and histopathological pictures. (a) Pedigree shows autosomal dominant inheritance. At birth, patient III-2 presented with: (b) 2 firm, flesh-coloured nodules on the back; and (c) 2 firm nodules on the scalp with necrotic evolution. Histopathological analyses of a removed dorsal nodule (patient III-2) showed a lesion located in the dermis and upper subcutis composed of both a spindle-shaped cell proliferation and a vascular proliferation. This angiomatous area, mostly seen at the periphery, is composed of more-or-less dilated capillaries arranged in a haemangiopericytoma-like pattern. The deep dermis is more cellular, less vascular and contains fibrosis. It is likely to be a regressing infantile myofibromatosis lesion (d: haematoxylin and eosin (HE) ×25). The periphery is composed of small myofibroblast fascicles arranged as rounded and hyalinized nodules. Beneath the periphery there are vascular channels, some exhibiting staghorn shapes. Between these the cells are poorly differentiated, polygonal or spindled (e: HE×50). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.