Medical Genetics, Experimental Medicine Department, University La Sapienza, S. Camillo-Forlanini Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy, Medical Pathophysiology Department, University La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy, I Division of Dermatology, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy, Laboratory of Molecular and Cell Biology, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy
Segmental neurofibromatosis 1 (SNF1) is a rare genodermatosis caused by somatic mutations in the NF1 gene. It consists of localized characteristic pigmentary lesions (i.e. café-au-lait spots and freckling) and/or neurofibromas intermingled with areas of unaffected skin, often configuring specific mosaic patterns. Oculo-auriculo-vertebral spectrum (OAVS) is a developmental field defect primarily affecting the 1
st and 2
nd branchial arch derivatives. This condition recognizes a wide range of environmental and genetic causes, including postzygotic mutations. We report on a 24-year-old female presenting with a constellation of features fitting both with SNF1 and OAVS. Neurofibromatosis 1 pigmentary lesions are confined to the left arm and adjacent trunk skin surface with sharp midline demarcation. OAVS characteristic craniofacial anomalies, including neurosensorial hearing loss, hemimandibular and tongue underdevelopment, are homolateral to the SNF1 features. Additional findings, such as prearicular tags and multiple costo-vertebral segmentation defects, mainly involving the cervical and upper thoracic metameres, support the diagnosis of OAVS. To our knowledge, this is the first published patient who presents with an association of SNF1 and OAVS. The spatial relationship between craniofacial and skin pigmentary anomalies has prompted us to speculate about the possible underlying pathogenetic mechanism (s).