Rachel Belk

A FAMILY STUDY AND THE NATURAL HISTORY OF PRENATALLY DETECTED UNILATERAL MULTICYSTIC DYSPLASTIC KIDNEY

PURPOSE We document the inheritance pattern of multicystic dysplastic kidney in 3 affected families and screen first-degree relatives of a cohort of children with prenatally detected multicystic dysplastic kidney for renal anomalies. The study also afforded an opportunity to document the natural history of prenatally detected multicystic dysplastic kidney. MATERIALS AND METHODS We identified 3 families during clinical treatment of children with prenatally detected multicystic dysplastic kidneys. Other members of these families were evaluated with renal ultrasonography. For the family screening study index cases were identified from a fetal uropathy database. A total of 94 first-degree relatives (52 parents, 35 full siblings and 7 half siblings) of 29 children with prenatally detected multicystic dysplastic kidneys were studied with urinary tract ultrasonography, blood pressure measurement, urinalysis and plasma biochemistry. RESULTS Two families had affected sibling pairs, 1 of which also had a half sibling with vesicoureteral reflux. The third family included 3 individuals with multicystic dysplastic kidney and 1 with renal agenesis thought to have resulted from involution of multicystic dysplastic kidney. This family is consistent with autosomal dominant inheritance with variable expressivity and reduced penetrance. In the screening study ultrasonography did not demonstrate significant renal anomalies in any of the 94 first-degree relatives of the multicystic dysplastic kidney index cases. Followup assessment of prenatally detected multicystic dysplastic kidneys in index cases demonstrated total involution in 52% at a median age of 6.5 years with no multicystic dysplastic kidney related morbidity. CONCLUSIONS Multicystic dysplastic kidney can be familial but is most commonly a sporadic anomaly. Formal screening of relatives is not recommended. Followup data on a cohort of children with prenatally detected multicystic dysplastic kidney add further support to conservative management.

BRCA1/2 predictive testing: a study of uptake in two centres

Differences in reported uptake of genetic testing for mutations in BRCA1 and BRCA2 can largely be accounted for by different methodologies and by studying research vs nonresearch families. In our joint study of 75 nonresearch families from two UK centres in which at least 3 years had elapsed since the initial proband had been informed of the availability of testing, only 45 and 34% of eligible individuals from Manchester and London, respectively, had come forward for counselling. Final uptake rates using a non-proactive approach were 53 and 29% for women and 11–12% for men, but the figure among those attending clinic was 73 and 62%, respectively. Unlike previous studies, we did not find that uptake had stabilised after a year with 25% of those being tested more than 2 years after the family was informed, and several delaying a considerable time between genetics appointments. We believe that the particularly low uptake even of counselling in men may need to be addressed by improving family communication or providing information sheets for family members to disseminate.

Better life expectancy in women with BRCA2 compared with BRCA1 mutations is attributable to lower frequency and later onset of ovarian cancer

Purpose: No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers. Methods: Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy. Results: Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers. Conclusion: Interventions to reduce ovarian cancer incidence are likely to have a greater effect on life expectancy in BRCA1 compared with BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1535–42)

Translation, validity and reliability of the British Sign Language (BSL) version of the EQ-5D-5L

PurposeTo translate the health questionnaire EuroQol EQ-5D-5L into British Sign Language (BSL), to test its reliability with the signing Deaf population of BSL users in the UK and to validate its psychometric properties.MethodsThe EQ-5D-5L BSL was developed following the international standard for translation required by EuroQol, with additional agreed features appropriate to a visual language. Data collection used an online platform to view the signed (BSL) version of the tests. The psychometric testing included content validity, assessed by interviewing a small sample of Deaf people. Reliability was tested by internal consistency of the items and test–retest, and convergent validity was assessed by determining how well EQ-5D-5L BSL correlates with CORE-10 BSL and CORE-6D BSL.ResultsThe psychometric properties of the EQ-5D-5L BSL are good, indicating that it can be used to measure health status in the Deaf signing population in the UK. Convergent validity between EQ-5D-5L BSL and CORE-10 BSL and CORE-6D BSL is consistent, demonstrating that the BSL version of EQ-5D-5L is a good measure of the health status of an individual. The test–retest reliability of EQ-5D-5L BSL, for each dimension of health, was shown to have Cohen’s kappa values of 0.47–0.61; these were in the range of moderate to good and were therefore acceptable.ConclusionsThis is the first time EQ-5D-5L has been translated into a signed language for use with Deaf people and is a significant step forward towards conducting studies of health status and cost-effectiveness in this population.

Clause 14(4)(9) of embryo bill should be amended or deleted

Amendments to the Human Fertilisation and Embryology Act 1990 are currently passing through the UK Houses of Parliament.1 Clause 14, section 4, number 9 (lines 23-30, page 10) says that people or embryos known to have a gene, chromosome, or mitochondrion abnormality that confers a significant risk of serious physical or mental disability, serious illness, or other serious medical condition must not be preferred over those not known to have an abnormality.

A qualitative exploration of trial-related terminology in a study involving Deaf British Sign Language users

BackgroundInternationally, few clinical trials have involved Deaf people who use a signed language and none have involved BSL (British Sign Language) users. Appropriate terminology in BSL for key concepts in clinical trials that are relevant to recruitment and participant information materials, to support informed consent, do not exist. Barriers to conceptual understanding of trial participation and sources of misunderstanding relevant to the Deaf community are undocumented.MethodsA qualitative, community participatory exploration of trial terminology including conceptual understanding of ‘randomisation’, ‘trial’, ‘informed choice’ and ‘consent’ was facilitated in BSL involving 19 participants in five focus groups. Data were video-recorded and analysed in source language (BSL) using a phenomenological approach.Results and discussionSix necessary conditions for developing trial information to support comprehension were identified. These included: developing appropriate expressions and terminology from a community basis, rather than testing out previously derived translations from a different language; paying attention to language-specific features which support best means of expression (in the case of BSL expectations of specificity, verb directionality, handshape); bilingual influences on comprehension; deliberate orientation of information to avoid misunderstanding not just to promote accessibility; sensitivity to barriers to discussion about intelligibility of information that are cultural and social in origin, rather than linguistic; the importance of using contemporary language-in-use, rather than jargon-free or plain language, to support meaningful understanding.ConclusionsThe study reinforces the ethical imperative to ensure trial participants who are Deaf are provided with optimum resources to understand the implications of participation and to make an informed choice. Results are relevant to the development of trial information in other signed languages as well as in spoken/written languages when participants’ language use is different from the dominant language of the country.

Reproductive liberty and deafness: Clause 14(4)(9) of embryo bill should be amended or deleted

Amendments to the Human Fertilisation and Embryology Act 1990 are currently passing through the UK Houses of Parliament.1 Clause 14, section 4, number 9 (lines 23-30, page 10) says that people or embryos known to have a gene, chromosome, or mitochondrion abnormality that confers a significant risk of serious physical or mental disability, serious illness, or other serious medical condition must not be preferred over those not known to have an abnormality.

Clause 14(4)(9) of embryo bill should be amended or deleted [Letter]

Amendments to the Human Fertilisation and Embryology Act 1990 are currently passing through the UK Houses of Parliament.1 Clause 14, section 4, number 9 (lines 23-30, page 10) says that people or embryos known to have a gene, chromosome, or mitochondrion abnormality that confers a significant risk of serious physical or mental disability, serious illness, or other serious medical condition must not be preferred over those not known to have an abnormality.

Response to editorial change and Stallworthy letter: Reproductive liberty and deafness: Clause 14(4)(9) of embryo bill should be amended or deleted

Amendments to the Human Fertilisation and Embryology Act 1990 are currently passing through the UK Houses of Parliament.1 Clause 14, section 4, number 9 (lines 23-30, page 10) says that people or embryos known to have a gene, chromosome, or mitochondrion abnormality that confers a significant risk of serious physical or mental disability, serious illness, or other serious medical condition must not be preferred over those not known to have an abnormality.

Reproductive Liberty and Deafness: Clause 14(4)(9) of the UK Human Fertilisation and Embryology Bill should be amended or deleted.

Amendments to the Human Fertilisation and Embryology Act 1990 are currently passing through the UK Houses of Parliament.1 Clause 14, section 4, number 9 (lines 23-30, page 10) says that people or embryos known to have a gene, chromosome, or mitochondrion abnormality that confers a significant risk of serious physical or mental disability, serious illness, or other serious medical condition must not be preferred over those not known to have an abnormality.