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THE CLINICAL PRESENTATION OF INDIVIDUALS WITH SUBTELOMERIC
DELETIONS: A RETROSPECTIVE CHART REVIEW
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| The subtelomeric regions of human chromosomes are the most gene rich regions in the human genome. Deletions in these regions have been identified in 5-7% of children with unexplained mental retardation or developmental delay. This study was performed as a retrospective chart review at the University of California, Los Angeles to identify the features and clinical presentations of individuals identified as carriers of a subtelomeric deletion. Medical records for patients seen in the UCLA Genetics Clinic for developmental delay, mental retardation, dysmorphic features, congenital anomalies, seizures, hypotonia, or autism from January 2003 through December 2004 were reviewed. Of the 178 patients meeting these criteria, 62 were tested by the UCLA Cytogenetics Laboratory for subtelomeric abnormalities using fluorescence in situ hybridization. Abnormalities were identified in seven (11.3%) of these individuals and included abnormalities of the 1p, 5q, 6q, 10q, 15q, and Xp subtelomeric regions. The phenotypes were subsequently described and compared to the findings within the literature. The patients with 1p, 5q, 6q, 10q, and Xp subtelomeric deletions fit within the spectrum of previously reported phenotypes. Detailed phenotypic information on 15q subtelomeric deletions is limited, and comparison was not possible. This study supported the high prevalence of subtelomeric deletions in children with mental retardation or developmental delay previously reported. | |
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ŇSHARING GENETIC TEST INFORMATION WITH FAMILY MEMBERSÓ |
| Hearing loss as a result of a variant in Connexin-26 and/or Connexin-30 provides as a common explanation for prelingual hearing loss. Clinical genetic testing is widely available to determine a possible explanation for a childŐs hearing loss. However, there is limited information regarding the effects of this genetic test information on families, including family dynamics and the sharing of test results. The purpose of this study was to get a better understanding of if, how, and why parents of children with hearing loss who have had Connexin-26 genetic testing share the genetic test information with family members. This study reports a qualitative analysis of 12 interviewed participants who are parents of a child with hearing loss who had genetic testing for Connexin-26 and Connexin-30 through the University of California, Los Angeles (UCLA) Genetics of Hearing Loss study. All (100%) of the participants, regardless of the outcome of the genetic test result, indicated sharing their childŐs genetic test result with at least one family member for a variety of reasons, however, 8 (66.7%) of the participants reported not sharing with at least one family member for other reasons. Regardless of the test result, some (41.7%) participants reported explaining the test result to family members to be a difficult task. These findings suggest that similar to the disclosure process of genetic information to family members in other conditions, individuals whose child had Connexin-26 and/or Connexin-30 genetic testing share genetic test information with close family members for a myriad of reasons depending on the genetic test result and, in response, get predictable reactions from relatives. | |
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AGENESIS OF THE CORPUS CALLOSUM:
EXAMINATION OF FUNCTIONAL INDEPENDENCE AND IMPACT ON FAMILY
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| The corpus callosum is the primary fiber tract that connects the left and right cerebral hemispheres. The connections provided by this structure allow for the integration of motor, sensory, and cognitive functions between the two hemispheres of the brain. Agenesis or dysgenesis of the corpus callosum (ACC/DCC) is one of the most commonly observed malformations of the human brain; it can occur as an isolated CNS malformation or as a component of over 50 characterized neurologic or systemic malformation syndromes. Despite the prevalence of ACC, very few of the specific causes of this condition are known, and prognosis can be difficult to determine. Furthermore, no published studies have examined the ability of the affected individual to produce change in the family. The purpose of this study was to quantitatively evaluate the level of independence in basic functions of daily living exhibited by individuals with ACC, as well as the primary caregiverŐs perception of the impact of ACC on the family system. We also aimed to identify and characterize relationships between and within these assessments. Results of telephone interviews with 53 primary caregivers revealed that individuals with ACC were less independent than expected for children their age without disability in each of the areas assessed, including self care, mobility, and cognition. Mothers reported that the presence of a child with ACC affected many areas of family life, including personal, social, and financial. However, despite this reported negative impact on the family in general, the familyŐs ability to cope with the hardships experienced seemed to remain intact. The level of independence exhibited by the proband was found to be significantly related to the amount of negative familial/social and financial impact sustained by the family. Furthermore, deficits in cognitive independence were more highly correlated with degree of negative social/familial impact than deficits in the areas of self care or mobility. The results of this study offer information to medical providers concerning which of the basic functions of daily living are most often compromised in individuals with ACC, as well as the degree to which these functions are affected. This study also outlines the areas of family life that are perceived to sustain the highest amount of negative impact. Our findings emphasize the importance of appropriate referrals to assist with management of negative impact on families, especially for families containing a child who experiences a greater degree of cognitive impairment. | |
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EVALUATION OF PRE-TEST PROBABILITY MODELS IN IDENTIFYING
hMLH1 AND hMSH2 MUTATIONS IN HNPCC:
A RETROSPECTIVE STUDY
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| Hereditary non-polyposis colorectal cancer (HNPCC) is the most common familial colorectal cancer syndrome and is thought to account for two to eight percent of all cases of the disease. There are several criteria available for the clinical diagnosis of HNPCC, some of which take into account the high risk of extra-colonic cancers in individuals with a mismatch repair (MMR) mutation. However, there is little data available of the probability of a MMR mutation in individuals suspected of having HNPCC. The purpose of this study was to evaluate the Wijnen (1998) pre-test probability model and the Myriad prevalence table (2004) at predicting mutations in individuals suspected of having HNPCC. A retrospective analysis was performed in 49 patients that were previously screened for germline mutations in both the hMLH1 and hMSH2 genes and enrolled in the City of Hope National Medical Center (COH) confidential registry (IRB #96144). Sensitivity, specificity, negative and positive predictive values, and areas under receiver operator characteristic (ROC) curves were calculated for the Wijnen model and Myriad table. Using a ten percent MMR gene mutation probability threshold, the Wijnen model and Myriad table performed poorly with both low sensitivities (55.6% and 60% respectively) and specificities (54.8% and 23.8% respectively). In addition, the calculated pre-test probabilities from the Wijnen model and Myriad table inadequately correlated with mutation prevelance, which is shown by the small areas underneath their ROC curves (0.616 and 0.400 respectively). As expected, the Bethesda guidelines showed a high sensitivity (94.4%) and unacceptebly low specificity (12.9%), while the Amsterdam criteria II had a sensitivity of (38.9%) and specificity of (71.0%). The results of this study demonstrate the need for an easy to use pre-test probability model that genetic counselors can use to accurately assess the likelihood of a MMR mutation in individuals suspected of having HNPCC. | |
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FETAL CHROMOSOME ABNORMALITIES RESULTING IN MISCARRIAGE IN OLDER AND YOUNGER WOMEN |
| Tn estimated 15-20% of all recognized pregnancies end in miscarriage. Chromosomal abnormalities account for at least 50% of all miscarriages and approximately 60% of pregnancies lost within the first trimester. The correlation between advanced maternal age and the likelihood of a fetal trisomy is well established. It is also known that trisomy leads to a high likelihood of spontaneous pregnancy loss. The purpose of this study was to investigate whether women of advanced maternal age have an increased likelihood of having experienced a miscarriage due to fetal trisomy. Analysis of 322 products of conception revealed that a finding of fetal trisomy was associated with a mean maternal age of 38 years, whereas a finding of fetal euploidy was associated with a mean maternal age of 33 years. This suggests that genetic counseling for pregnancy loss should differ, depending on maternal age. The second part of the study was designed to investigate the impact of these results on genetic counseling; it was determined that many genetic counselors are knowledgeable about the relationship between maternal age and fetal trisomy, and counsel women accordingly. | |
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Interest in Genetic Testing for Spinocerebellar Ataxia: A Descriptive Analysis of the Motives among Symptomatic and at-Risk Individuals |
| The motives for genetic testing for some neurodegenerative diseases have been well studied, yet little is known about why someone might test for spinocerebellar ataxia (SCA). The aim of this study is to determine the reasons for and against genetic testing for SCA. This investigation surveyed 42 individuals either affected by SCA or at-risk of getting SCA. The survey quantitatively assessed participantsŐ levels of agreement with potential reasons for and against testing. It was expected that results would be similar to those reported in the literature for other neurodegenerative diseases. Participants were recruited at a California ataxia research meeting, though ataxia support groups, and though the National Ataxia FoundationŐs website. The majority of participants had already completed testing and were symptomatic at that time. The main testing motives for symptomatic individuals were to establish a diagnosis of SCA and to reduce uncertainty about the future. The main testing motives for presymptomatic individuals were to know if their children were at-risk, to know if they needed to save for future expenses, to collaborate with research to help others, and to reduce uncertainty about the future. The reasons for not wanting testing included fear of insurance discrimination and concerns about future implications for participantsŐ families. These findings suggest that motives for testing for SCA are similar to those found in other neurodegenerative diseases. Knowledge of these motives can help genetic counselors better understand their patients who test for SCA and can enable them to help at-risk individuals make informed decisions about genetic testing. | |
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PSYCHOSOCIAL EVALUATION OF FAMILIES AFFECTED BY MUCOPOLYSACCHARIDOSIS I |
| DMucopolysaccharidosis I (MPS I) is a rare, autosomal recessive, lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDUA), an enzyme that is responsible for breaking down glycosaminoglycans (GAG). In MPS I, GAG accumulates in the cells, leading to irreversible cellular and tissue damage. The phenotypes for MPS I range from the severe form of Hurler syndrome to the less severe form of Scheie syndrome. Patients with Hurler syndrome have many medical problems, in which respiratory, cardiac, and joint problems may severely restrict mobility and the ability to perform activities of daily living. Most patients die by the age of 10 years. Initially, until the 1980s, palliative and nonspecific therapies were the only options for treatment. The only two disease-specific treatments available are bone marrow transplantation (BMT) and enzyme replacement therapy (ERT), both of which are not curative. Physiological studies have been done to test the effectiveness of ERT, yet no published studies have examined the psychosocial effects of treatment on the patient and the family. The purpose of this study was to explore the social and emotional impact the disease and treatment has on the family affected by MPS I. Five primary care givers of children with MPS I participated in tape-recorded interviews focused on obtaining diagnosis, family, and treatment information as well as eliciting experiences with and feeling about having a child diagnosed with MPS I. Results from this study indicate that despite the obstacles and time invested in enzyme replacement therapy, the families feel that ERT is worth the effort because either the children or the parents gain some sort of benefit, whether it is physiological, social or emotional. Given the financial and social implications of ERT, the results of this study suggest that health care professionals need to evaluate criteria set for determining when a patient should discontinue treatment. | |
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Perceived Risk of Breast Cancer and Adherence to Screening Guidelines in Armenian American
Women
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| TAn increased risk perception of breast cancer development and more favorable attitudes toward screening practices have been previously reported to be associated with adherence to breast cancer screening guidelines. Information regarding relevant cancer screening guidelines is an important component of cancer genetic counseling sessions. Genetic counselors in the Los Angeles area serve a culturally diverse community, and acquiring an awareness of the perceptions of distinct populations may enhance communication in the health care setting. Los Angeles County holds one of the largest Armenian communities in America. No published studies have examined the risk perceptions and attitudes of Armenian Americans with respect to breast cancer and screening. The purpose of this study was to determine the relationship of risk perception and attitudes towards breast cancer screening practices in Armenian American women. The information obtained from the study may enhance risk communication in genetic counseling sessions. Surveys of 58 Armenian American women from four different organizations in the Greater Los Angeles area were administered to assess demographic characteristics, cultural attributes, risk perception, attitudes towards screening, screening practices, attitudes towards genetic counseling, and interactions with health care providers. Attitudes towards screening were measured by the willingness to perform screening and the worry associated with screening. Simultaneous multiple regression analysis was performed and demonstrated no relationship of numeric risk perception, affective risk perception, willingness to perform screening, and worry related to screening practice with adherence to breast cancer screening guidelines. The values of R_ for breast self-examination, clinical breast examination, and mammography screening were 0.036, 0.064, and 0.183, respectively. A fear of bad results was cited as the most common cause of worry about screening, reluctance to practice screening, and disinterest in genetic counseling. Future research should delineate the factors contributing to risk perception and adherence to breast cancer screening guidelines in Armenian American women. | |
