PA15 Becker naevus syndrome associated with a mosaic pathogenic variant in ACTB

Abstract

Abstract A 15-year-old girl presented with an 8-year history of a gradually enlarging, irregular, nonconfluent hyperpigmented patch on her left flank. The lesion demonstrated an area of increased hair growth, did not cross the midline and was mildly pruritic but otherwise asymptomatic. Another pigmented patch, present since birth, was also noted on her right lower back and was consistent with a café-au-lait macule. Medical history included a marfanoid phenotype with musculoskeletal complications including scoliosis and joint hypermobility, for which she was under the care of the orthopaedic team for bilateral patellar instability associated with recurrent dislocation. She was also noted to have increased skin laxity, mild pectus excavatum, mitral valve prolapse and symptomatic tachyarrhythmias. She was born at term, to nonconsanguineous parents, with no postnatal developmental concerns. There was a family history of an older brother with significant scoliosis and hip dysplasia requiring hip replacements, developing from the age of 14 years. Genetic testing was negative for FBN1 and five other genes associated with Marfan syndrome. Thyroid function and bone profile were normal. Menarche occurred at 11 years of age, and a full hormone profile was normal except for a mildly raised prolactin level, deemed to be a normal variant in puberty. Abdominal and pelvic ultrasounds were normal. Skin biopsy from the left flank revealed orthokeratosis, irregular elongation of rete ridges and sparse perivascular chronic inflammation in the superficial dermis. Next-generation sequencing and droplet digital polymerase chain reaction from DNA extracted from skin revealed de novo mosaic pathogenic variants in ACTB, which encodes β-actin, an intracellular protein involved in cell migration, signalling and proliferation. Recurrent mosaic variants in ACTB have previously been associated with 61% of Becker naevi and one case of Becker naevus syndrome in one study (Cai ED, Sun BK, Chian A et al. Postzygotic mutations in beta-actin are associated with Becker’s nevus and Becker’s Nevus syndrome. J Invest Dermatol 2017; 137:1795–8), as well as congenital smooth muscle hamartomas and odontomaxillary dysplasia. Our patient had cutaneous and extracutaneous features suggestive of Becker naevus syndrome. This rare syndrome predominantly involves skeletal and soft tissue abnormalities, with breast hypoplasia most frequently reported. Notable features here include a café-au-lait macule, scoliosis and pectus excavatum. This case highlights the value of DNA analysis from skin in confirming a diagnosis, after 9 years of presentation to paediatric services. Given the heterogeneous extracutaneous phenotypes, there are also important implications for counselling and screening of associated conditions.