Prenatal diagnosis for haemophilia: A nationwide survey among female carriers in the Netherlands

Carriers of haemophilia face difficult choices regarding prenatal diagnosis, but little is known about the determinants that influence their decisions. The aim of this study was to assess the incidence of prenatal diagnosis and potential determinants affecting the choice for prenatal diagnosis. A nationwide survey was performed among all women who underwent carriership testing for haemophilia in the Netherlands between 1992 and 2004. Prenatal diagnosis was assessed i

The use of preventive health care services: Carrier testing for the genetic disorder haemophilia

A retrospective study was performed to explore carrier testing among women who were possible or obligate carriers of the haemophilia gene. Knowledge of the possibility of carrier testing and use of carrier testing were studied separately. In our exploration we were guided by the diffusion theory and the Health Belief Model. Logistic regression analysis showed that four factors were statistically significant related to knowledge of carrier testing: information via mass media, a haemophilic relative in the nuclear family rather than in the extended family, medical severity of haemophilia, and information from the patients' organization. For those women acquainted with carrier testing two of the four factors just mentioned were significantly related to the utilization of carrier testing i.e. having a haemophilic relative in the nuclear family and the medical severity of the haemophilia. In addition the following factors were associated: attitude towards abortion because of haemophilia, educational level, and marital status. Notwithstanding the prominent function of the mass media and the patients' organization, the respondents themselves stated that relatives, especially parents and sisters, were the most important source of information on genetic counselling and carrier testing.genetic counceling prevention carrier testing haemophilia help-seeking behaviour health beliefs diffusion theory

Increased Urinary Excretion of 3-Methoxytyramine in Patients with Head and Neck Paragangliomas

Context: Patients with head-and-neck paragangliomas (HNPGL) are regularly screened for catecholamine excess. The clinical relevance of increased urinary secretion of 3-methoxytyramine is unclear in HNPGL. Objective: The aim of the study was to assess the prevalence and the clinical, biochemical, and radiological presentation of patients with HNPGL with increased urinary excretion of 3-methoxytyramine. Patients and Methods: A total of 136 consecutive patients with HNPGL were included and screened for catecholamine excess by measurement of 24-h urinary excretion of (nor) metanephrine, (nor) epinephrine, vanillylic mandelic acid, dopamine, and 3-methoxytyramine. In patients with catecholamine excess, abdominal/intrathoracic paragangliomas were excluded by I-123-metaiodobenzyl-guanidine scintigraphy, magnetic resonance imaging, and/or computed tomography. Results: Urinary 3-methoxytyramine excretion was increased in 31 of the 136 patients (23%). In 18 of these 31 patients, this was the only sign of biochemical activity of HNPGL. Dopamine excretion was higher in subjects with increased 3-methoxytyramine excretion (1.62 +/- 0.1 mu mol/24 h vs. 2.5 +/- 0.3 mu mol/24 h; P < 0.01). Of the 136 HNPGL patients, 21 (15%) had excessive excretion of at least one catecholamine and/or their metabolites when 3-methoxytyramine excretion was not taken into account. With the inclusion of patients with excessive 3-methoxytyramine excretion, 39 (29%) had excessive catecholamine excretion. Patients with 3-methoxytyramine excess had significantly more complaints of palpitations (P < 0.01), diaphoresis (P = 0.03), collapse (P < 0.05), and a higher pulse rate (P < 0.01). Increased excretion of 3-methoxytyramine was not associated with particular types of HNPGL or genotypes. Conclusions: A substantial number of HNPGL patients have biochemically active tumors, reflected in increased excretion of 3-methoxytyramine, associated with increased dopamine excretion. Some patients only display increased excretion of 3-methoxytyramine, but not of other catecholamines or their metabolites. (J Clin Endocrinol Metab 95: 209-214, 2010)Otorhinolaryngolog

Pheochromocytomas detected by biochemical screening in predisposed subjects are associated with lower prevalence of clinical and biochemical manifestations and smaller tumors than pheochromocytomas detected by signs and symptoms

Context: Sporadic pheochromocytomas are detected by clinical signs and symptoms, whereas pheochromocytomas in patients with a known hereditary predisposition for these tumors are detected by repetitive screening for catecholamine excess. Objective: To document the clinical, biochemical, and pathological differences between patients with sporadic pheochromocytomas, detected by signs and symptoms and patients with pheochromocytomas, detected by biochemical screening in established hereditary syndromes. Design: Retrospective follow-up study. Patients and methods: We included 60 consecutive patients diagnosed with pheochromocytoma (pheochromocytomas detected by signs and symptoms: n=28 and pheochromocytomas detected by screening: n=32) in our center. Results: Patients with pheochromocytomas detected by screening presented with less complaints of diaphoresis (P<0.01), palpitations (P=0.01), paleness (P=0.01), nausea (P<0.01), and vomiting (P=0.01) compared with patients with symptomatic pheochromocytomas. Patients with pheochromocytomas detected by screening tended to be younger at the time of diagnosis (41+/-2 vs 47+/-3 years, P=0.07). In addition, patients with pheochromocytomas detected by screening had significantly lower rates of 24-h urinary catecholamine excretion, and considerably smaller tumors (3.7+/-0.5 vs 7.3+/-0.7 cm, P<0.01). Conclusions: Pheochromocytomas detected by screening of patients with a hereditary predisposition have a much lower prevalence of signs and symptoms, lower catecholamine excess, and smaller tumors, compared with sporadic pheochromocytomas, detected by signs and symptoms. These data support the benefits of screening for pheochromocytomas in patients with hereditary syndromes predisposing for these tumors.Hereditary cancer genetic

Pheochromocytomas detected by biochemical screening in predisposed subjects are associated with lower prevalence of clinical and biochemical manifestations and smaller tumors than pheochromocytomas detected by signs and symptoms

Context: Sporadic pheochromocytomas are detected by clinical signs and symptoms, whereas pheochromocytomas in patients with a known hereditary predisposition for these tumors are detected by repetitive screening for catecholamine excess. Objective: To document the clinical, biochemical, and pathological differences between patients with sporadic pheochromocytomas, detected by signs and symptoms and patients with pheochromocytomas, detected by biochemical screening in established hereditary syndromes. Design: Retrospective follow-up study. Patients and methods: We included 60 consecutive patients diagnosed with pheochromocytoma (pheochromocytomas detected by signs and symptoms: n=28 and pheochromocytomas detected by screening: n=32) in our center. Results: Patients with pheochromocytomas detected by screening presented with less complaints of diaphoresis (P<0.01), palpitations (P=0.01), paleness (P=0.01), nausea (P<0.01), and vomiting (P=0.01) compared with patients with symptomatic pheochromocytomas. Patients with pheochromocytomas detected by screening tended to be younger at the time of diagnosis (41+/-2 vs 47+/-3 years, P=0.07). In addition, patients with pheochromocytomas detected by screening had significantly lower rates of 24-h urinary catecholamine excretion, and considerably smaller tumors (3.7+/-0.5 vs 7.3+/-0.7 cm, P<0.01). Conclusions: Pheochromocytomas detected by screening of patients with a hereditary predisposition have a much lower prevalence of signs and symptoms, lower catecholamine excess, and smaller tumors, compared with sporadic pheochromocytomas, detected by signs and symptoms. These data support the benefits of screening for pheochromocytomas in patients with hereditary syndromes predisposing for these tumors.Otorhinolaryngolog

Prenatal diagnosis for haemophilia: a nationwide survey among female carriers in the Netherlands

Clinical epidemiolog

Psychological distress and use of psychosocial support in familial adenomatous polyposis

Objective: Familial adenomatous polyposis (FAP) is characterized by multiple adenomas in the colorectum with a high risk to develop colorectal cancer. It is unclear whether individuals at risk of FA P experience distress due to this potentially life-threatening disease. This nationwide study assessed: (I) the prevalence of psychological distress; and (2) the need for and use of specialized professional psychosocial support. Methods: In this cross-sectional study, all individuals from families at high risk for FAP registered at the Netherlands Foundation for the Detection of Hereditary Tumours were invited to complete a questionnaire assessing, among other issues, generalized, cancer-specific and FAP-specific distress. Results: In total, 525 individuals completed the questionnaire. Approximately 20% of the respondents had moderate to severe levels of FAP-specific distress. Levels of generalized distress were comparable to the general Dutch population. Significantly more individuals with a FAP diagnosis had frequent cancer worries than those at risk of FAP or non-carriers (p = 0.02). Distress levels were more strongly associated with psychosocial variables (e.g. perceived cancer risk), than with sociodemographic or clinical variables. Up to 43% of the variance in distress could be explained by all variables combined. Of those moderately to severely distressed, 26% had received specialized professional psychosocial support, while 30% of those did not receive the support they wanted. Conclusions: A substantial minority of individuals reported moderate to severe distress levels associated with FAP. However, only one-third of those received specialized professional psychosocial support. We recommend the use of a screening questionnaire to identify individuals in need of such support. Copyright (C) 2009 John Wiley & Sons, Ltd.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Mutations in SDHD are the major determinants of the clinical characteristics of Dutch head and neck paraganglioma patients

OBJECTIVE Head and neck paragangliomas (HNPGL) are associated with mutations in genes encoding subunits of succinate dehydrogenase (SDH). The aim of this study was to evaluate SDH mutations, family history and phenotypes of patients with HNPGL in the Netherlands. DESIGN We evaluated the clinical data and the mutation status of 236 patients referred between 1950 and 2009 to Leiden University Medical Center. RESULTS The large majority of the patients carried mutations in SDHD (83%), and the p.Asp92Tyr Dutch founder mutation in SDHD alone accounted for 72% of all patients with HNPGL. A mutation in SDHAF2 was found in 4%, mutations in SDHB in 3% and a mutation in SDHC was identified in a single patient (0·4%). Over 80% of patients presented with positive family history, of whom 99·5% carried a mutation in an SDH gene. SDH mutations were also found in 56% of isolated patients, chiefly in SDHD (46%), but also in SDHB (8%) and SDHC (2%). The clinical parameters of these different subgroups are discussed: including the age at diagnosis, associated pheochromocytomas, tumour multifocality and malignancy rate. CONCLUSION The majority of Dutch patients with HNPGL present with a positive family history, in contrast to other European countries. The clinical characteristics of patients with HNPGL are chiefly determined by founder mutations in SDHD, the major causative gene in both familial and isolated patients with HNPGL. The high frequency of founder mutations in SDHD suggests a higher absolute prevalence of paraganglioma syndrome in the Netherlands.Hereditary cancer genetic