Happle R, Torrelo A
Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
Department. of Dermatology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
J Eur Acad Dermatol Venereol. 2020 Nov;34(11):2511-2517. doi: 10.1111/jdv.16603. Epub 2020 Jul 21.
In patients with tuberous sclerosis, we can today distinguish between two different categories of segmental mosaicism. The well-known simple segmental mosaicism is characterized by a unilateral or otherwise localized arrangement of the ordinary lesions of the disorder, reflecting heterozygosity for an early postzygotic new mutation. By contrast, superimposed mosaicism is defined by a pronounced segmental involvement in a patient with ordinary non-segmental lesions of the same disorder, resulting in a heterozygous embryo from loss of the corresponding wild-type allele that occurred at a very early developmental stage. So far, the second category has been called 'type 2 segmental mosaicism', but here we propose the short and unambiguous term 'superimposed mosaicism'. In order to render physicians familiar with the manifold manifestations of this category as noted in tuberous sclerosis, we review the following clinical designations under which cases suggesting superimposed mosaicism have been published: forehead plaque; shagreen patch; fibrous cephalic plaque; fibromatous lesion of the scalp; folliculocystic and collagen hamartoma; segmental hypomelanosis; congenital segmental lymphedema; and segmental 'diffuse' lipomatosis. Molecular corroboration of this genetic concept has been provided in a case of forehead plaque and in a child with shagreen patch. - Extracutaneous manifestations suggesting superimposed mosaicism include columnar tuberous brain defects; 'radial migration lines' or 'cerebral white matter migration lines' as noted by brain imaging; linear hamartomatous lesions of the tongue; fibrous dysplasia of bones including macrodactyly; and unilateral overgrowth of an arm or leg. - Remarkably, superimposed mosaicism appears to occur in tuberous sclerosis far more frequently than simple segmental mosaicism.
在结节性硬化症患者中，如今我们可以区分出两种不同类型的节段性镶嵌现象。众所周知的单纯节段性镶嵌现象的特征是，该疾病的普通病损呈单侧或其他局限性分布，这反映了合子后早期新突变的杂合性。相比之下，叠加性镶嵌现象的定义是，在患有同一疾病的普通非节段性病损的患者中，出现明显的节段性受累，这是由于在非常早期的发育阶段相应野生型等位基因丢失，导致胚胎成为杂合子。到目前为止，第二类现象一直被称为“2型节段性镶嵌现象”，但在此我们提出一个简短且明确的术语“叠加性镶嵌现象”。为了让医生熟悉结节性硬化症中这一类型的多种表现，我们回顾了以下临床名称，在这些名称下曾发表过提示叠加性镶嵌现象的病例：前额斑块；鲛鱼皮斑；头皮纤维斑块；头皮纤维瘤性病变；毛囊囊肿性和胶原性错构瘤；节段性色素减退；先天性节段性淋巴水肿；以及节段性“弥漫性”脂肪瘤病。前额斑块病例和患有鲛鱼皮斑的儿童病例已提供了这一遗传概念的分子确证。——提示叠加性镶嵌现象的皮肤外表现包括柱状结节性脑缺损；脑成像显示的“放射状移行线”或“脑白质移行线”；舌部线性错构瘤性病变；包括巨指（趾）症在内的骨纤维发育不良；以及单侧上肢或下肢过度生长。——值得注意的是，叠加性镶嵌现象在结节性硬化症中的出现频率似乎远高于单纯节段性镶嵌现象。
