Summary Skin disease can cause severe disability and handicap in children. Measurement of the impact of skin disease on the quality of life is required to aid clinical decision‐making, for clinical research, for audit of paediatric dermatology services, and for political reasons, to aid arguments for more resources for the care of children with skin disease. Adult measures are inappropriate, as the lives of children differ markedly from those of adults. The purpose of this study was to create and initially validate a simple practical questionnaire for use in children. One hundred and sixty‐nine children, aged 3–16 years, attending a paediatric dermatology clinic, wrote down, with the help of their parents, all the ways in which their skin disease affected their lives. One hundred and eleven different aspects were identified; 10 questions were composed to cover these aspects, using a structure similar to the Adult Dermatology Life Quality Index. This draft questionnaire was piloted on two series, totalling 40 children, and minor alterations were made to improve clarity. The Children's Dermatology Life Quality Index (CDLQI) questionnaire (maximum score 30) was then given to a further 233 dermatology paediatric out‐patients (CDLQI mean = 5.1, SD = 4.9), 47 normal controls (mean 0.4, 0.7) and 55 control patients attending a general paediatric clinic (mean 0.7, 2.5). The CDLQI scores for eczema (mean = 7.7, 5.6, n = 47), psoriasis (5.4, 5.0, n = 25) and acne (5.7, 4.4, n = 40), were all highly significantly greater than for moles and naevi (2.3, 2.9, n = 29). The highest mean score was that for scabies (mean = 9.5, 10.5, n = 6). Overall, the highest scoring questions (each maximum score 3) related to symptoms (mean = 1.05, n = 233), feelings (0.90), swimming and sports (0.51), sleep (0.49) and treatment effects (0.47), with the question on effects on friendships (0.18) scoring least. Forty‐six additional patients completed the CDLQI on two occasions, with a 4‐day interval to check reliability of test‐retesting. The standard deviation of the differences between pairs (2.5) was substantially less than the standard deviation of the measurements themselves (before = 4.79, after = 5.08). confirming acceptable repeatability. This study has confirmed the major impact of widespread inflammatory skin disease, in particular atopic eczema, on the quality of life of children. Although further validation is required, the CLDQI provides a new technique for comparative purposes.

Little information is available about the effect of childhood atopic dermatitis (AD) on family function. The aim of this study was to identify the areas of family life most affected and their perceived importance. Intensive qualitative interviews with 34 families were conducted and 11 basic problem areas were identified. A detailed questionnaire was prepared, part of which addressed the perceived importance of particular issues using the framework of multi-attribute utility theory. The results from using this questionnaire in 41 families were analysed and a shorter 10-question one-page Dermatitis Family Impact (DFI) questionnaire designed (maximum score = 30). In affected families the mean DFI score was 9.6 +/- 7.0 (range 0-27, n = 56) and in unaffected families the mean score was 0.4 +/- 0.9 (range 0-3, n = 26, P < 0.0001). The DFI could potentially be used as an extra measure in clinical studies, or to help guide appropriate management of AD.

Using the CLQI we have shown that HRQL impairment in children with chronic skin disease is at least equal to that experienced by children with many other chronic diseases of childhood, with AD and psoriasis having the greatest impact on HRQL among chronic skin disorders and only cerebral palsy scoring higher than AD. Cross-validation of the CLQI with the CDLQI in the group of children with skin disease demonstrates a strong linear association and good agreement between the two.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.