講演情報
[P19-3]良性家族性カフェオレ斑からNeurofibromatosis type1と診断された家族例
○中藤 大輔1, 小野 伊久美2, 三須 久美子2, 山田 茉未子1, 鈴木 寿人1, 宮 冬樹1, 武内 俊樹3, 小崎 健次郎1 (1.慶應義塾大学 医学部 臨床遺伝学センター, 2.慶應義塾大学病院, 3.慶應大学 医学部 小児科学教室)
[Background] Neurofibromatosis type 1(NF1) and Legius syndrome (LS) are caused by a pathogenic variant of the NF1 gene and the SPRED1 gene respectively. Cafe-au-lait macules (CALMs) represent essential clinical feature of both disorders and appear by 3 months of age. The natural history of the two disorders is distinctive after puberty: Cutaneous neurofibromas and nodular plexiform neurofibromas develop in NF1, but never in LS. Here, we report a family who had LS-like benign history characterized only CALMs, but had heterozygous NF1 pathogenic variant of the variant NF1 gene. [Case] The proband is a woman in her 30s. She, her mother, and proband’s first child had CALMs without accompanying symptoms. After the birth of her second affected child, the family was referred to our genetic clinic. The proband was diagnosed as having LS. Unexpectedly, genetic testing showed that the proband had a heterozygous pathogenic variant in the NF1:c.2970_2972del but no pathogenic variants in the SPRED1 gene. [Discussion] We reported a family history with clinical diagnosis of LS and multiple CALMs and NF1 pathogenic variant p.(M992del). In general, genotype-phenotype correlation is not apparent in the NF1 gene. However literature review showed that p.(M992del) variant represents an exception in that patients with p.(M992del) of the NF1 gene develop multiple CALMs but never neurofibromas. We recommend to add screening for p.(M992del) of the NF1 gene to SPRED1 variant analysis when one aims to rule in LS.