Cuell A, Bansal N, Cole T, Kaur M R, Lee J, Loffeld A, Moss C, O'Donnell M, Takeichi T, Thind C K, McGrath J A
Department of Dermatology, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, UK.
Department of Dermatology, Solihull Hospital, Heart of England NHS Foundation Trust, Solihull, UK.
Clin Exp Dermatol. 2015 Dec;40(8):860-4. doi: 10.1111/ced.12702. Epub 2015 Jul 14.
Familial progressive hyper- and hypopigmentation (FPHH) is an autosomal dominant skin condition presenting in childhood with generalized macular dyspigmentation, usually reported in patients of East Asian origin. It overlaps phenotypically with other dyschromatoses, but can now be distinguished by mutations in the KIT ligand gene (KITLG).
We report two unrelated white families with similar phenotypic presentations of FPHH developing in early childhood in several generations.
Sanger sequencing of the exons and flanking introns of KITLG was performed.
This identified a new heterozygous missense mutation in each family (p.Thr34Asn and p.Val37Gly, respectively). Of the six affected individuals examined by us, two had cancer: a 62-year-old man in family 1 had developed two primary melanomas and a pharyngeal carcinoma, and a 42-year-old woman in family 2 had developed thyroid carcinoma. All had unusually sparse lateral eyebrows, a finding not previously reported in this condition.
We summarize the genetic spectrum of the dyschromatoses and discuss a possible increased risk of malignancy in FPHH.
家族性进行性色素沉着过多和过少症（FPHH）是一种常染色体显性遗传性皮肤病，在儿童期表现为全身性黄斑色素沉着异常，常见于东亚裔患者。它在表型上与其他色素沉着异常症有重叠，但现在可通过KIT配体基因（KITLG）的突变来区分。
我们报告两个不相关的白人家族，几代人中均有儿童期发病且具有相似FPHH表型表现。
对KITLG的外显子和侧翼内含子进行桑格测序。
在每个家族中均鉴定出一个新的杂合错义突变（分别为p.Thr34Asn和p.Val37Gly）。在我们检查的6名受影响个体中，有2人患癌：家族1中的一名62岁男性患了两种原发性黑色素瘤和一种咽癌，家族2中的一名42岁女性患了甲状腺癌。所有人的外侧眉毛都异常稀疏，这一发现在此病症中此前未见报道。
我们总结了色素沉着异常症的遗传谱，并讨论了FPHH中可能增加的恶性肿瘤风险。
