A novel PHF6 mutation results in enhanced exon skipping and mild Börjeson-Forssman-Lehmann syndrome.
Explore the source record for details and available documents.
Abnormalities, Multiple↗
Biomedical subjects
A G Hunter
Publications and source records attributed to A G Hunter.
Ethical, legal, and practical concerns about recontacting patients to inform them of new information: the case in medical genetics.
There is a consensus among medical geneticists that it is desirable to recontact patients as new information becomes available. Furthermore, some have suggested that there are legal arguments to support an obligation, creating a duty to recontact. Thus far much of the discussion among medical geneticists has focused on the practical concerns of implementing such a policy. However, we think that any such policy raises a number of important ethical concerns that must first be considered. Furthermore, there has not been a careful evaluation of the legal precedents that may reflect on a hypothetical duty to recontact. In this paper we first present an analysis of the scope of approaches and issues to be addressed in the development of ethical policy on this question. Secondly, we examine whether there is a legal obligation to recontact former patients about advances in genetics, as well as the legal implications if such a policy were to be adopted. Finally, we consider some of the functional and resource implications of adopting a policy of recontact. Our goal is to provide a framework for further discussion of this question and to stimulate further debate and research.
Data Collection↗
Low rate of adequate folic acid supplementation in well-educated women of high socioeconomic status attending a genetics clinic.
Explore the source record for details and available documents.
Adult↗
APC I1307K increases risk of transition from polyp to colorectal carcinoma in Ashkenazi Jews.
BACKGROUND & AIMS: The I1307K allele of the APC gene has been shown to confer a modestly elevated risk of colorectal cancer in the Ashkenazi Jewish population (relative risk, 1.5-1.7). However, it is unclear whether the alteration predisposes to adenomas and whether the genetic information can be used in clinical practice. To further address the pathogenic significance of I1307K, we offered both a genetic test and a screening program to individuals considered to be at increased risk for colorectal cancer. We compared the prevalence of polyps and their characteristics between carriers and noncarriers. METHODS: Invitations to participate in a DNA and colonoscopy screening program were mailed, together with a family questionnaire, to 3540 households forming the Jewish Community in Ottawa. The I1307K variant was analyzed in 242 eligible respondents who were selected because they had a personal or family history of colon cancer. Nearly 80% of these respondents (n = 189; age range, 32-83 years) consented to undergo a single colonoscopic examination. RESULTS: The overall carrier frequency of I1307K in the study group was 10.3%. A higher proportion of heterozygous gene carriers was found in the subgroup of colon cancer survivors (27%) than among asymptomatic individuals (8%, P < 0.02). A total of 59 polyps were identified in 44 subjects. Histologically confirmed adenomatous polyps were diagnosed in 11.8% of carriers and 12.8% of noncarriers (P > 0.5). No significant differences in polyp size, multiplicity, location, degree of villosity, or age-dependent prevalence were found between the 2 groups of participants. CONCLUSIONS: The high frequency of I1307K colorectal cancer patients found in the Ashkenazi Jewish community of Ottawa and the equivalent proportion of carriers and noncarriers who developed adenomatous polyps suggest that in this community, I1307K is associated with a significant predisposition to carcinoma but not adenoma.
Adenomatous Polyps↗
Outcome of the routine assessment of patients with mental retardation in a genetics clinic.
This study reviewed hospital and genetics clinic records of 411 patients evaluated in our department from 1986 to 1997 inclusive. Major objectives were to establish how often and under what circumstances a specific genetic/syndrome diagnosis was made and to determine the value of laboratory tests in the hope of gaining a more selective approach to referral, evaluation, and use of the laboratory. A specific genetic/syndrome diagnosis was made in 19.9% of cases, and in a further 4.4% the referring diagnosis was eliminated but no new diagnosis made. There was a significant excess of affected males (277:134) and of affected male sib pairs over expectation, suggesting an additional, potentially important, contribution from nonspecific X-linked mental retardation (MR). Factors associated with making a diagnosis included referral from a pediatrician or neurologist, absence of cerebral palsy, presence of more than three minor anomalies and/or an unusual appearance, a recognizable Gestalt or key anomaly. There was a linear relationship between the likelihood of making a diagnosis and the number of minor anomalies. Factors not associated with making a diagnosis included the year when the patient was seen, degree of MR, number of prior specialists seen, presence of a major malformation, occurrence of seizures, and a head circumference either <3rd or >97th centile. Although chromosome studies were somewhat less likely to be ordered in patients with less severe MR, the positive rate was unaffected by the severity of the MR. The rate of abnormal results was positively correlated with the presence of minor anomalies and/or an unusual appearance. None of 134 studies carried out on patients with </=3 minor anomalies alone were positive. Fragile X studies were less likely to be ordered with increasing levels of MR and 10 of 14 positive test results were among those with mild delay. Thirteen of 14 diagnoses were based on Gestalt. Molecular and fluorescence in situ hybridization studies had a positive rate of >60% when ordered by a clinical geneticist compared with 0% when ordered by other physicians. Results showed that use of the laboratory was inconsistent and not clearly based on the findings in a particular child. Significant changes in patterns of referral and the evaluation process could be made that would result in significant economies of time and laboratory use and a minimum level of missed diagnoses.
Child↗
A pilot study of the possible role of familial defects in anticoagulation as a cause for terminal limb reduction malformations.
Terminal limb deficiency defects affect between three and eight babies per 10000 births and are an important cause of disability. Established causes for these malformations include single gene disorders, chromosome abnormalities, teratogens, and amniotic bands. However, the etiology remains unknown in a significant proportion of cases. Several authors have hypothesized that vascular accidents, either bleeds or vessel occlusions, may underlie a substantial number of cases; but, for the most part, the origin of such events remains obscure. Over the past several years, an increasing number of genetic thrombophilias have been recognized and have been associated with increased risks of peri- and post-natal occlusive disease, and with higher rates of recurrent pregnancy loss. The hypothesis to be examined in this pilot study was whether the inherited thrombophilias might be associated with a vascular cause of some terminal limb deficiency defects. Towards that end, protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin (G20210A) variant, methylenetetrahydrofolate reductase variant, plasma homocysteine, anticardiolipin IgM and IgG antibodies, and lipoprotein (a) were measured in 24 mother-child pairs in which the child had a terminal limb defect. The results provided some evidence that there may be an excess of thrombophilias present in such families and that they may play some etiological role in a subset of these types of limb malformations.
Antibodies, Anticardiolipin↗
A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center.
The medical community and general population have become aware that genetic testing is available to look for BRCA1 and BRCA2 mutations. However, criteria for who should be referred for genetic counseling and possible subsequent testing have yet to be determined, and many genetics centers have been overwhelmed by the demand for service. We set out to develop a family history assessment tool (FHAT) that could be used by physicians to select individuals for genetic counseling. Arbitrarily, we chose individuals who would have an approximate doubling of their lifetime risk for breast or ovarian cancer. The FHAT was then applied to 184 unrelated families, with an index patient who had breast or ovarian cancer and who had accepted the offer of BRCA1 BRCA2 testing. Data were compiled to compare the number of individuals who would have been referred for genetic counseling and the number of mutation-positive individuals who would have been screened out from counseling using FHAT, the tables from Claus, and the BRCAPRO system. In this population, FHAT was effective in minimizing both the number of referrals and the likelihood of missing women who were later found to be mutation-positive.
Adult↗
Why patients do not attend for their appointments at a genetics clinic.
Explore the source record for details and available documents.
Adolescent↗
Clinical and radiological assessment of a family with mild brachydactyly type A1: the usefulness of metacarpophalangeal profiles.
The brachydactylies are a group of conditions in which various subtypes have been defined based upon the specific pattern of digital bones involved. Type A1 brachydactyly is principally characterised by maximal involvement of the middle phalanges. We report an extended family with a mild brachydactyly A1 which was, except for some short stature, not associated with any of the additional clinical findings reported in several published families. While all the hand bones tended to be small, the principal features of the affected members were shortened middle and distal phalanges, proximal 1st phalanges, and 5th metacarpals. The feet were similarly involved and tended to have a broad, slightly adducted forefoot. The two affected children showed multiple coned epiphyses. This paper provides a detailed description of the family including the radiographic signs and metacarpophalangeal profiles, which proved to be useful in distinguishing the mildly affected persons.
Adolescent↗
Perceptions of the outcome of orthopedic surgery in patients with chondrodysplasias.
As part of a larger survey of patients with chondrodysplasias, 197 patients or their parents were asked whether they had undergone orthopedic surgery related to their chondrodysplasia and, if so, to rate their impression of the outcome. Seventy-four patients (37.6%) had undergone a total of 152 procedures (221 if concurrent bilateral operations are counted separately). The percentage of patients treated surgically ranged from a low of 8.3% for hypochondroplasia to a high of 87.5% for diastrophic dysplasia. Of the patients who had surgery, the mean number of procedures per patient ranged from 1.0 for hypochondroplasia to 2.69 for pseudoachondroplasia. Of 180 individual procedures related to the limbs, the outcome in 88.8% was judged 'a bit better' or higher and in 68.8% 'much better' or higher. The responses ranged from a low of 70.4 and 66.7%, respectively for proximal femoral osteotomies to a high of 100 and 85.9% for hip replacement. The comparable figures for spine related surgery were 81.8 and 48.5% with a low of 58.3 and 50.0% for foramen magnum-cervical surgery and a high of 93.8 and 43.8% for thoracolumbar procedures. The expressed perception of lack of satisfaction varied not only by procedure but by diagnosis. Overall, patients perceived a high level of post-surgical improvement, although a number experienced subsequent deterioration and the need for further intervention.
Adolescent↗
Some psychosocial aspects of nonlethal chondrodysplasias: I. Assessment using a Life-Styles Questionnaire.
Studies concerning the psychosocial aspects of skeletal dysplasias that cause disproportionate short stature have been few and have usually involved small numbers of patients. As part of a study involving patients with chondrodysplasias and their families, an assessment battery of standardised instruments designed to measure depression, anxiety, self-esteem, personal support networks, marital adjustment, and family structure were completed by patients and, in many cases, their sibs, spouses, and/or parents. This first in a series of six papers reports the results of a Life-Styles Questionnaire which provides some insights into the levels of satisfaction with various aspects of life, including friendships, employment, the use of some substances and services, and the impact of the skeletal dysplasia on career, marriage, and childbearing. Results are presented for patients and the unaffected parents of patients. Overall, the study has shown a high level of satisfaction with many aspects of life. However, there are important differences in attitudes between the married and unmarried patients, and in some cases the unaffected parents, in a number of areas including health, overall satisfaction with life, and concerns surrounding child bearing and employment.
Adolescent↗
Some psychosocial aspects of nonlethal chondrodysplasias: VI. Assessment of family interaction using the FACES II Questionnaire.
Intrafamilial dynamics, including those between parents, and between parents and their children, have an important influence on the ultimate success or failure of a child's becoming a well adapted and socially integrated individual. Disability and/or birth defects, such as dwarfism, may alter family functioning, either because of the psychological impact or the day-to-day functional demands or both. Family cohesiveness and adaptability and communication have been identified as key variables that define how a family interacts. The Circumplex Model of Family Systems defines the role of these factors in the family dynamic and the FACES II scale provides a standardised assessment of their level of function within the family. Thus families can be classified by their degree of cohesion, adaptability, and the combination of the two. This article reports on the results of the FACES II assessment that was completed by 107 patients with disproportionate short stature due to a chondrodysplasia, as well as by a variable number of their parents, sibs, or spouses.
Adolescent↗
Some psychosocial aspects of nonlethal chondrodysplasias: II. Depression and anxiety.
Individuals with chondrodysplasias may have disproportionate short stature and in some cases a distinctive facial appearance. These physical signs have the potential of affecting parent-child interactions and those of the dwarfed person with broader society. Depression and anxiety are two psychological symptoms with potential for a major impact on a person's functioning within society. In this study depression and anxiety were assessed using the Beck Depression Inventories and the Spielberger State-Trait Anxiety Inventories. While in general depression did not appear more likely in dwarfs than in the general population, comparison of adult patients with their unaffected sibs did raise some concern. Also, having an unaffected parent or spouse appeared to be associated with higher depression scores. Adult trait anxiety levels appeared higher, especially among women, than normally expected in the general population and when compared with their unaffected sibs.
Adolescent↗
Some psychosocial aspects of nonlethal chondrodysplasias: III. Self-esteem in children and adults.
Self-esteem is considered one of the most important personality attributes. It correlates with physical and mental health and the ability to cope with stress. The attitudes of others, and the experiences of interacting with them, are considered as playing a major role in the development of self-esteem. Thus, those patients with disproportionate short stature due to a chondrodysplasia can reasonably be considered to be at risk of developing low self-esteem. In this study, self-concept and self-esteem were measured in 159 children and adults with various chondrodysplasias and disproportionate short stature. The results from the children did not suggest that they had a lower concept of self than did their unaffected sibs or a sample of average-size persons. By contrast, although the adults did not differ significantly from a population sample, they scored significantly below their unaffected sibs. There also appeared to be a trend to lower scores among women, patients who had had an unaffected parent, and those who were married to an unaffected spouse, although none of those differences were statistically significant.
Adult↗
Some psychosocial aspects of nonlethal chondrodysplasias: IV. Dyadic scale of marital adjustment.
This article examines marital adjustment of couples who have had a child with dwarfism due to a skeletal dysplasia, and of couples where one or both members are dwarfs. The instrument used was the Dyadic Adjustment Scale developed by Spanier [1976: Marriage Family 38:15-38]. The reasons for examining this psychosocial aspect of dwarfism were that the birth of a dwarfed child to average-size parents might be expected to cause stress in the relationship, and because several authors had raised concerns about the nature and/or quality of marriages involving dwarfs. This study provides evidence of a decrease in the level of marital adjustment for the average-size parents of affected children, gives tentative reassurance about marriages where both individuals are dwarfs, but raises some concerns about couples where only one member is a dwarf.
Adult↗
Some psychosocial aspects of nonlethal chondrodysplasias: V. Assessment of personal social support using the Personal Resource Questionnaire.
Social support has been shown to be an important influence on how an individual copes with a number of stresses, including acute and chronic illness, psychiatric morbidity, and life events. It can be thought of as a dynamic process consisting of a network of persons who are available to provide support, and the level of support that is perceived to be available from those persons. Patients with disproportionate short stature due to a chondrodysplasia might be expected to face greater challenges in developing a social support network. This study assessed social support among a group of dwarfed patients using the Personal Resource Questionnaire (PRQ85). The overall extent and functioning of social support appears comparable to that in the general population, but there are some differences when unmarried patients are compared with married patients and when those who have affected spouses are compared with those whose spouses are of average stature.
Adult↗
Heterozygote advantage of the MTHFR gene in patients with neural-tube defect and their relatives.
Explore the source record for details and available documents.
Abortion, Spontaneous↗
Medical complications of achondroplasia: a multicentre patient review.
Achondroplasia is the most prevalent chondrodysplasia and numerous authors have documented the varied social and medical complications that may compromise a full and productive life. Complications include cervicomedullary compression, spinal stenosis, restrictive and obstructive lung disease, otitis media, and tibial bowing, among others. These known complications have led to recommendations for the anticipatory management of such patients. There are relatively few data on the actual rates and timing of these problems. This paper reports data on the rates and age of occurrence of several of these complications based on a review of recorded chart information of 193 patients ascertained from several well established genetic centres with a known interest in the chondrodysplasias. The length of follow up varied and the rates of occurrence at specific age intervals were used to estimate the cumulative percentage affected for each complication. The report includes information on otitis media, ventilation tubes, hearing loss, tonsillectomy, speech problems, tibial bowing and osteotomy, ventricular shunting, apnoea, cervicomedullary decompression, and neurological signs attributable to spinal stenosis.
Achondroplasia↗