Dermatological Manifestations of Inherited Cancer Syndromes in Children

A. Karalis; M. Tischkowitz; G.W.M. Millington

Disclosures

The British Journal of Dermatology. 2011;164(2):245-256. 

In This Article

Abstract and Introduction

Abstract

Various cutaneous signs presenting in childhood, for example café-au-lait macules, may have systemic cancer associations. Indeed, this may be the first manifestation of the underlying cancer predisposition. The syndromes covered in this review fall into four main categories: (i) DNA damage processing defects including Fanconi anaemia, ataxia telangiectasia, Bloom syndrome, Rothmund–Thomson syndrome, constitutional mismatch repair defects and xeroderma pigmentosum; (ii) signalling pathway defects, including naevoid basal cell carcinoma and Costello syndromes; (iii) primary immunodeficiency syndromes; and (iv) syndromes that do not fit this molecular classification, such as X-linked dyskeratosis congenita. This review focuses on the dermatological findings of these conditions. Some of these conditions exhibit a milder heterozygous phenotype and this should be elicited in the family history. Where the dermatological findings are subtle, a targeted family history can provide clues towards making a diagnosis. Nondermatological features of each condition are summarized too, together with molecular testing strategies, which will direct genetic counselling and screening. This review will enable the dermatologist and other clinicians in the early recognition and molecular confirmation of underlying cancer-predisposing syndromes. This allows the possibility of surveillance and prevention strategies to be initiated in a timely manner, in affected children and other at-risk family members.

Introduction

Our understanding of familial cancer syndromes is increasing rapidly, with the emphasis shifting towards early detection of at-risk families.[1–4] A careful family history may identify this rare but important group of patients.[1–4] Cutaneous findings are often the first presentation, so cases may first appear in the dermatology clinic.[2] Note that the familial cancer syndromes and other genodermatoses associated with cancer discussed here do not necessarily strictly represent a 'syndrome' in the classic sense, i.e. the association of several clinically recognizable features each linked with an identical molecular pathology.[4]

We divide the inherited syndromes into four categories: (i) DNA repair defects[5,6] (Fig. 1), which are predominantly autosomal recessive; (ii) signalling defects that are either autosomal dominantly inherited (e.g. Gorlin syndrome[7]) or caused by new mutations (e.g. Costello syndrome[8]); (iii) conditions where primary immunodeficiency leads to both malignancy and cutaneous stigmata;[9] and (iv) a miscellaneous group of syndromes that do not fit this molecular classification. Each syndrome is summarized in Table 1. Many of the conditions discussed in this article have café-au-lait macules (CALMs) as a cutaneous manifestation (Table 1). However, CALMs are also found in a number of other genetic conditions in the absence of malignancy risk, as well as most commonly as a sporadic, isolated normal finding (Table 2). We have recently reviewed the dermatological manifestations of inherited cancer syndromes presenting predominantly in adults, namely Muir–Torre syndrome, Gardner syndrome, familial melanoma, Peutz–Jeghers syndrome, Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Birt–Hogg–Dubé syndrome and hereditary leiomyomatosis/renal cell cancer, so these are not discussed in this article.[2]

Figure 1.

An overview of the different types of DNA damage processing mechanisms which can lead to hereditary cancer predisposition syndromes with dermatological features. UV, ultraviolet. Modified from Hoejmakers.101

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