Quintáns B, Pardo J, Campos B, Barros F, Volpini V, Carracedo A, Sobrido M J
University Clinical Hospital of Santiago de Compostela-SERGAS, Spain.
Case Rep Neurol. 2011 Apr 11;3(1):86-90. doi: 10.1159/000327557.
Neurofibromatosis type 1 (NF1) is a multisystem disease with autosomal dominant inheritance and complete penetrance diagnosed by clinical findings. Cutaneous neurofibromas are present in almost all adult patients in the dermis, epidermis or along the peripheral nerves. Plexiform neurofibromas are subcutaneous or deep lesions involving nerve plexuses or roots. Neurofibromas can degenerate into malignant tumors, with important prognostic implications. NF1 shows a broad clinic variability even within a single family. Exceptions are cases reporting the in-frame microdeletion c.2970_2972delAAT, presenting with the typical pigmentary features of NF1, but no cutaneous or plexiform neurofibromas. We report a patient with a de novo c.2970_2972delAAT mutation who had few café-au-lait spots, only 2 of which measured >15 mm, axillary and submammary freckling, a flat angioma extending over the neck, arm and trunk, a high arched palate, micrognathia, macrocephaly, pes cavus and scoliosis. There was complete absence of observable cutaneous neurofibromas as well as external plexiform neurofibromas. She had had epileptic seizures since childhood; however, a diagnosis of NF1 had not been confirmed until she was 38, partly due to the paucity of characteristic cutaneous stigmata. We confirm the association of the c.2970_2972delAAT mutation in NF1 with a particular clinical phenotype, especially with lack of detectable neurofibromas. For an appropriate management of patients and family counseling, molecular study of the NF1 gene should be considered in patients not fulfilling NIH criteria when other features suggestive of NF1 are present. In the absence of neurofibromas, starting NF1 testing with the screening of exon 17 may be worthwhile.
1型神经纤维瘤病（NF1）是一种常染色体显性遗传且具有完全外显率的多系统疾病，通过临床症状进行诊断。几乎所有成年患者的真皮、表皮或沿周围神经都存在皮肤神经纤维瘤。丛状神经纤维瘤是涉及神经丛或神经根的皮下或深部病变。神经纤维瘤可恶变为恶性肿瘤，具有重要的预后意义。即使在单个家族中，NF1也表现出广泛的临床变异性。例外情况是报告框内微缺失c.2970_2972delAAT的病例，这些病例具有NF1的典型色素沉着特征，但无皮肤或丛状神经纤维瘤。我们报告了一名患有新发c.2970_2972delAAT突变的患者，其咖啡斑较少，其中只有2个直径大于15毫米，腋窝和乳腺下有雀斑，颈部、手臂和躯干有一个扁平血管瘤，高拱腭、小颌畸形、巨头畸形、高弓足和脊柱侧弯。完全没有可观察到的皮肤神经纤维瘤以及外部丛状神经纤维瘤。她自幼患有癫痫发作；然而，直到38岁才确诊为NF1，部分原因是特征性皮肤体征较少。我们证实了NF1中c.2970_2972delAAT突变与特定临床表型的关联，特别是与缺乏可检测到的神经纤维瘤有关。为了对患者进行适当管理和提供家庭咨询，当存在其他提示NF1的特征但不符合美国国立卫生研究院（NIH）标准的患者时，应考虑对NF1基因进行分子研究。在没有神经纤维瘤的情况下，从第17外显子开始进行NF1检测可能是值得的。
