Burch Joanna M, Fassihi Hiva, Jones Catherine A, Mengshol Sarah C, Fitzpatrick James E, McGrath John A
Department of Dermatology, University of Colorado Health Sciences Center, Denver, USA.
Arch Dermatol. 2006 May;142(5):620-4. doi: 10.1001/archderm.142.5.620.
Kindler syndrome (KS) is a rare genetic disorder that is characterized by blistering in infancy, followed by the onset of poikiloderma and photosensitivity in childhood. The recently elucidated molecular pathogenesis involves mutations in KIND1, a gene encoding the protein kindlin-1, which is involved in the attachment of the actin cytoskeleton to the extracellular matrix in basal keratinocytes.
We describe a child with the neonatal diagnosis of epidermolysis bullosa simplex who developed poikiloderma and skin fragility at 6 years of age. His skin showed diminished staining with anti-kindlin-1 antibody, and genetic analysis revealed that he was a compound heterozygote with a previously unreported mutation in KIND1. Ultrastructural clues to the diagnosis of KS were present in a biopsy specimen that was obtained when the patient was 10 months old, before he developed poikiloderma and photosensitivity.
In this case, a combination of a known mutation (R271X) and a newly described mutation (1755delT) in the KIND1 gene produced loss of function in kindlin-1, leading to the clinical features of KS. Ultrastructural findings characteristic of KS were evident years before the onset of poikiloderma and sun sensitivity. In infancy, electron microscopy can enable early, accurate diagnosis of KS.
Kindler综合征（KS）是一种罕见的遗传性疾病，其特征为婴儿期出现水疱，随后在儿童期出现皮肤异色症和光敏性。最近阐明的分子发病机制涉及KIND1基因突变，该基因编码蛋白kindlin-1，其参与基底角质形成细胞中肌动蛋白细胞骨架与细胞外基质的附着。
我们描述了一名新生儿期诊断为单纯性大疱性表皮松解症的儿童，其在6岁时出现皮肤异色症和皮肤脆弱。他的皮肤抗kindlin-1抗体染色减弱，基因分析显示他是一个复合杂合子，在KIND1基因中有一个以前未报道的突变。在该患者出现皮肤异色症和光敏性之前10个月时获取的活检标本中存在KS诊断的超微结构线索。
在本病例中，KIND1基因中已知突变（R271X）和新描述的突变（1755delT）共同导致kindlin-1功能丧失，从而产生KS的临床特征。在皮肤异色症和日光敏感性出现数年之前，KS特征性的超微结构发现就已很明显。在婴儿期，电子显微镜检查能够实现KS的早期准确诊断。
