Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.
Am J Med Genet C Semin Med Genet. 2023 Jun;193(2):109-115. doi: 10.1002/ajmg.c.32055. Epub 2023 Jun 8.
In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of heterozygosity, probably during the first week after fertilization. In biallelic phenotypes, such overlaying mosaic involvement may coexist with disseminated mosaicism, for example, in neurofibromatosis or tuberous sclerosis. In other phenotypes, however, classical nonsegmental involvement tends to appear much later, which is why the superimposed mosaic is a heralding feature. In Brooke-Spiegler syndrome (eccrine cylindromatosis), a large pedigree documented a 5-year-old boy with multiple, congenital small eccrine cylindromas along the lines of Blaschko. Disseminated cylindromas were absent because they usually appear in adulthood. ̶ In Hornstein-Knickenberg syndrome, an affected woman had an 8-year-old son with a nevus comedonicus-like lesion exemplifying a forerunner of the syndrome. ("Birt-Hogg-Dubé syndrome" represents a nonsyndromic type of hereditary perifollicular fibromas.) In glomangiomatosis, neonatal superimposed mosaicism is a heralding feature because disseminated lesions appear during puberty or adulthood. Linear porokeratosis is a harbinger of disseminated porokeratosis that develops 30 or 40 years later. ̶ Cases of superimposed linear Darier disease were forerunners of nonsegmental manifestation. ̶ In a case of Hailey-Hailey disease, neonatal mosaic lesions heralded nonsegmental involvement that began 22 years later.
在常染色体显性皮肤疾病中,杂合子胚胎在受精后第一周内可能由于早期杂合性丢失而出现明显的镶嵌性受累,新生儿中有时会出现这种情况。在双等位基因表型中,这种重叠的镶嵌性受累可能与弥漫性镶嵌性共存,例如神经纤维瘤病或结节性硬化症。然而,在其他表型中,经典的非节段性受累往往出现得更晚,这就是为什么重叠的镶嵌性是一个预示特征。在布鲁克-斯皮格尔综合征(大汗腺瘤病)中,一个大型家系记录了一名 5 岁男孩,他沿着 Blaschko 线有多发性先天性小汗腺圆柱瘤。弥漫性圆柱瘤不存在,因为它们通常在成年后出现。在霍恩斯坦-克尼克伯格综合征中,一名受影响的女性有一个 8 岁的儿子,他有一个类似于粉刺瘤样的病变,这是该综合征的先驱。(“Birt-Hogg-Dubé 综合征”代表一种遗传性毛囊周围纤维瘤的非综合征型。)在血管球瘤病中,新生儿重叠镶嵌性是一个预示特征,因为弥漫性病变在青春期或成年期出现。线状角层松解症是随后出现的弥漫性角层松解症的先兆,后者在 30 或 40 年后发展。重叠的线状 Darier 病病例是节段性表现的先驱。在一例 Hailey-Hailey 病中,新生儿镶嵌性病变预示着随后 22 年开始的非节段性受累。