Systematic search for neutropenia should be part of the first screening in patients with poikiloderma

Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund–Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia, gingivitis, nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails. Previously undetected and silent neutropenia was evidenced after C16orf57 molecular analysis. Neutropenia was absent in the C16orf57-negative patients. This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis.

► Differential diagnoses of Rothmund–Thomson syndrome include Clericuzio-type Poikiloderma.
► 10 patients with syndromic poikiloderma and negative for RECQL4 were investigated for C16orf57.
► Two heterozygous nonsense mutations were identified in a child presenting with previously undetected neutropenia.
► Neutropenia was absent in the C16orf57-negative patients.
► Neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene, prior to RECQL4.