Paternal Family History Research Articles

Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease.

Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy.1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries.2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother. This results in infant morbidity and substantial healthcare expenditure.4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic. Both hypertension and proteinuria implicate the endothelium as the target of the disease. The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance.5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost.7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown. The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop. Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers. When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes. Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis.10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops.12 Approximately 20% of …

Australian Women’s Perceptions of Breast Cancer Risk Factors and the Risk of Developing Breast Cancer

Background Numerous studies have shown that the majority of women overestimate both their own risk and the populations’ risk of developing breast cancer. A number of factors have been found to correlate with perceived risk. Methods This paper reports on a telephone survey of a nationally representative sample of approximately 3,000 Australian women aged 30 to 69 years, conducted in 2007, and compares the findings with those of a similar survey conducted in 2003. Results There was a clear tendency for respondents to overestimate the proportion of women who will develop breast cancer during their lifetime. Approximately half the respondents perceived themselves as being at the same risk of developing breast cancer as other women their age; older respondents were more likely to perceive themselves to be at a lower than average risk. Family history was recognized as a risk factor for breast cancer, although there was evident confusion in relation to risk from paternal family history. It was also evident that the association between age and risk status is poorly understood, and misconceptions of breast cancer risk factors identified in the previous survey persisted in 2007. Conclusion Overall, these results suggest that there remains an educational challenge if we seek to increase the accuracy of women’s perceptions of their risk for developing breast cancer, primarily in relation to the significance of age and family history as breast cancer risk factors.

Breast and Ovarian Cancer: The Forgotten Paternal Contribution

Five to 10% of all cases of breast and ovarian cancer are attributed to a heritable genetic predisposition. Transmission of BRCA1 and BRCA2 mutations is equally likely through maternal or paternal lineage; however, fewer referrals to cancer genetics clinics appear to be made for a paternal, than maternal, family history of breast and/or ovarian cancer. To examine this potential bias, a retrospective review of 315 patient and family charts was conducted by one familial cancer clinic in Toronto, Canada. Referral letters, risk estimates, and family histories were analyzed to identify significant differences between patients referred with maternal and paternal family histories. It was determined that patients are approximately five times more likely to be referred with a maternal family history of breast and/or ovarian cancer as compared to those with a paternal family history (p = <.0001). Individuals with a paternal family history were found to have a different, and higher, pattern of risk estimates (p = .00064). No significant difference was seen between the type of referrals sent by general practitioners, oncologists, and gynecologists. Recommendations to increase the awareness of paternal family history in assessing cancer risk are provided.

Structural brain changes in normal individuals with a maternal history of Alzheimer's

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH-) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH-, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH- in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH- and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.

Components of family history associated with women's disease perceptions for cancer: A report from the Family Healthware™ Impact Trial

PurposeTo determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. MethodsBaseline, cross-sectional data on 2,505 healthy women aged 35–65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. ResultsParticipants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel “spillover” effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. ConclusionsUnderstanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions.

P.1.e.028 Increase of whole brain volume and gray and white matter tissue in OCD: a volumetric and voxel-based morphometry MRI study

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH−) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH−, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH− in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH− and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.

Maternal Family History of Diabetes Is Associated With a Reduced Risk of Cardiovascular Disease in Women With Type 2 Diabetes

OBJECTIVETo investigate whether parental family history of diabetes influences cardiovascular outcomes in type 2 diabetes.RESEARCH DESIGN AND METHODSWe studied 1,294 type 2 diabetic patients (mean age 64.1 years, 51.2% female) recruited to a community-based cohort study from 1993 to 1996 and followed until mid-2006. A data linkage system assessed all-cause and cardiac mortality, incident myocardial infarction, and stroke. Cox proportional hazards modeling was used to determine the influence of maternal or paternal family history on these outcomes.RESULTSA maternal family history of diabetes was reported by 20.4% of the cohort, 8.3% reported paternal family history, and 2.0% reported both parents affected. Maternal and paternal family history was associated with earlier age of diabetes onset, and maternal family history was associated with worse glycemic control. For all patients, maternal family history was significantly associated with reduced risk of all-cause mortality and cardiac mortality. When analyzed by sex, maternal family history had no effect on male patients, whereas female patients with diabetic mothers had significantly reduced hazard ratios for death from all causes (0.63 [95% CI 0.41–0.96]; P = 0.033), for death from cardiac causes (0.32 [0.14–0.72]; P = 0.006), and for first myocardial infarction (0.45 [0.26–0.76]; P = 0.003). Paternal family history status was not associated with these outcomes.CONCLUSIONSA maternal family history of diabetes confers relative protection against cardiovascular disease in female patients but not in male patients with type 2 diabetes. Paternal family history is associated with risks equivalent to those without a family history of diabetes. Some of the clinical heterogeneity of type 2 diabetes is related to maternal transmission effects with differential impact on male and female patients.

Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor among cognitively normal (NL) individuals. This (11)C-Pittsburgh Compound B (PiB)-PET study examines whether NL individuals with LOAD parents show increased fibrillar amyloid-beta (Abeta) deposition, a hallmark of Alzheimer's disease (AD) pathology and whether there are parent-of-origin effects. Forty-two 50- to 80-year-old NL persons were examined with PiB-PET. These individuals included 14 NL subjects with a maternal family history (FH) of LOAD (FHm), 14 NL subjects with a paternal FH (FHp), and 14 NL subjects with a negative family history of any dementia (FH-). Statistical parametric mapping and automated regions-of-interest were used to compare cerebral-to-cerebellar PiB standardized uptake value ratios, reflecting fibrillar Abeta burden, across groups. FH groups did not differ in age, gender, education, and apolipoprotein E (ApoE) status. NL FHm subjects showed higher PiB retention in AD-affected anterior and posterior cingulate cortex (PCC), precuneus, parietal, temporal, occipital, and frontal cortices, right basal ganglia, and thalamus, compared with FH- and FHp subjects. FHp subjects showed increased PiB retention in the PCC and frontal cortex, intermediate between FHm and FH- subjects. Results remained significant after controlling for age, gender, education, and ApoE status. Children of parents with LOAD, particularly those with affected mothers, have increased fibrillar Abeta load in AD-vulnerable regions compared with controls, perhaps accounting for the known increased risk for AD. Present findings may motivate further research on familial transmission and parent-of-origin effects in LOAD.

The Effect of Parental Transmission of Diabetes on the Development of Gestational Diabetes Mellitus

The Effect of Parental Transmission of Diabetes on the Development of Gestational Diabetes Mellitus

Maternal transmission of Alzheimer's disease: Prodromal metabolic phenotype and the search for genes

After advanced age, having a parent affected with Alzheimer's disease (AD) is the most significant risk factor for developing AD among cognitively normal (NL) individuals. Although rare genetic mutations have been identified among the early-onset forms of familial AD (EOFAD), the genetics of the more common forms of late-onset AD (LOAD) remain elusive. While some LOAD cases appear to be sporadic in nature, genetically mediated risk is evident from the familial aggregation of many LOAD cases. The patterns of transmission and biological mechanisms through which a family history of LOAD confers risk to the offspring are not known. Brain imaging studies using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) have shown that NL individuals with a maternal history of LOAD, but not with a paternal family history, express a phenotype characterised by a pattern of progressive reductions of brain glucose metabolism, similar to that in AD patients. As maternally inherited AD may be associated with as many as 20 per cent of the total LOAD population, understanding the causes and mechanisms of expression of this form of AD is of great relevance. This paper reviews known genetic mutations implicated in EOFAD and their effects on brain chemistry, structure and function; epidemiology and clinical research findings in LOAD, including in vivo imaging findings showing selective patterns of hypometabolism in maternally inherited AD; possible genetic mechanisms involved in maternal transmission of AD, including chromosome X mutations, mitochondrial DNA and imprinting; and genetic mechanisms involved in other neurological disorders with known or suspected maternal inheritance. The review concludes with a discussion of the potential role of brain imaging for identifying endophenotypes in NL individuals at risk for AD, and for directing investigation of potential susceptibility genes for AD.

Nurses transforming health care using genetics and genomics

Nurses are well positioned to incorporate genetic and genomic information across all aspects of the United States (U.S.) health care system. Nurses, the most trusted health professionals [1], make unique contributions to the field of human genetics and genomics and complement the work of other health care providers to improve the health of the public. Health care benefits greatly from the unprecedented and ongoing work elucidating the genetic/genomic basis of health, illness, disease risk, and treatment response. The progress in genetics and genomics is applicable to the entire spectrum of health care and all health professionals and as such to the entire nursing profession (2.9 million) [2] in the United States regardless of role, clinical specialty, or academic preparation. The majority of disease risk, health conditions and the therapies used to treat those conditions have a genetic and/or genomic element influenced by environmental, lifestyle, and other factors therefore impacting the entire nursing profession [3]. Nurses have intimate knowledge of the patient’s, family’s, and community’s perspectives; an understanding of biologic underpinnings; experience with genetic/genomic technologies and information; skills in communication and building coalitions; and most importantly, the public’s trust. Across the lifespan, nursing focuses on health promotion and disease prevention, which is an integral component of genetic/genomic health care practices. Awareness of nurses’ strengths and skills, together with the recognition that prevention is the hallmark of genetic/genomic health care, will inform public policymaking groups as they address issues that affect heath care practice in the area of genetics/genomics. Policy making process will be informed with new insights will be gained with inclusion of nurses and professional nursing organizations. These policies can facilitate the ability of U.S. health care systems to use genetic/genomic knowledge to promote health and manage disease.

Risk factors for paternal vertical transmission of hepatitis B virus.

To explore the risk factors of and the influence of different hepatitis B virus (HBV) DNA load on paternal vertical transmission of HBV. Totally, 161 HBsAg negative women, whose husband was HBsAg positive, attended the antenatal clinics of the Provincial Maternity and Child Health Hospital of Fujian from September 2007 to December 2008 and their newborns were selected, and the epidemiologic information, the duration of being a HBV carrier, the first class HBV family history of the fathers, HBV markers, HBV DNA load, HBsAb of the gravidas, the outcomes of the newborns were all collected. Cord blood was sampled after delivery for HBV DNA quantification and those with HBV DNA load >/= 1.0 x 10(3) copy/ml were chosen as the case group and those < 1.0 x 10(3) copy/ml as control. (1) Among the 161 newborns, 36 HBV DNA positive cord blood samples were detected, giving a rate of 22.4% (36/161) for paternal vertical transmission of HBV. The HBV DNA positive rate in cord blood was 32.0% (23/72) in HBeAg-positive fathers and 14.6% (13/89) in HBeAg-negative fathers. (2) Univariate analysis showed that HBeAg-positive, HBV DNA positive, first class family history of HBV and the duration of being a HBV carrier of the fathers were risk factors of paternal HBV vertical transmission [chi(2) = 6.892, 29.916, 29.499 and 23.821, OR = 2.7, 5.2, 8.3 and 1.4 (P < 0.01)]. (3) Multivariate analysis found that paternal serum HBV DNA positive and the first class family history of HBV of the father side were risk factors of paternal vertical transmission of HBV (OR = 11.1, 95%CI: 4.6 - 27.1; OR = 17.1, 95%CI: 3.5 - 82.6). (4) According to the different serum HBV DNA load of the HBsAg-positive father, 7 groups were divided. A dose dependent effect was found that the HBV DNA positive rate of the cord blood increased with the rising of HBV DNA load. No HBV DNA positive cord blood was detected when paternal HBV DNA load was < 1.0 x 10(4) copy/ml, while 100% of the cord blood were positive when paternal HBV DNA load >/= 1.0 x 10(8) copy/ml. (5) The average birth weight of the newborns in the two groups was the same (3.3 +/- 0.4) kg. And the delivery mode, gestational age at delivery, height and Apgar score of the newborns at 1 minute, neonatal pathological jaundice and other complications had no significant difference between the two groups (P > 0.05). No relationship was found between the neonatal outcomes and the paternal HBV vertical transmission (P > 0.05). HBV DNA load in the serum of HBsAg-positive father, and the paternal first class family history of HBV are risk factors of paternal HBV vertical transmission. When the serum HBV DNA load in HBsAg-positive father is >/= 1.0 x 10(7) copy/ml, the possibility of paternal vertical transmission of HBV would increase.

Genetic assessment of breast cancer risk in primary care practice

Family history is increasingly important in primary care as a means to detect candidates for genetic testing or tailored prevention programs. We evaluated primary care physicians' skills in assessing family history for breast cancer risk, using unannounced standardized patient (SP) visits to 86 general internists and family medicine practitioners in King County, WA. Transcripts of clinical encounters were coded to determine ascertainment of family history, risk assessment, and clinical follow-up. Physicians in our study collected sufficient family history to assess breast cancer risk in 48% of encounters with an anxious patient at moderate risk, 100% of encounters with a patient who had a strong maternal family history of breast cancer, and 45% of encounters with a patient who had a strong paternal family history of breast and ovarian cancer. Increased risk was usually communicated in terms of recommendations for preventive action. Few physicians referred patients to genetic counseling, few associated ovarian cancer with breast cancer risk, and some incorrectly discounted paternal family history of breast cancer. We conclude that pedigree assessment of breast cancer risk is feasible in primary care, but may occur consistently only when a strong maternal family history is present. Primary care education should focus on the link between inherited breast and ovarian cancer risk and on the significance of paternal family history. Educational efforts may be most successful when they emphasize the value of genetic counseling for individuals at risk for inherited cancer and the connection between genetic risk and specific prevention measures.

Why do some fathers become primary caregivers for their infants? A qualitative study

Despite recent advances, research on father-infant relations is still relatively lacking. One hitherto neglected area is the subjective experience of primary caregiving (PCG) fathers, including their reasons for taking on a PCG role. Twenty-five PCG fathers, defined as those providing sole child care for their 1-year-old infant for at least 20 waking hours a week, completed semi-structured interviews as part of a large two-centre English study of child care. Interviews were tape-recorded, transcribed and analysed using emergent theme analysis. Themes with a bearing on the fathers' explicit and implicit reasons for providing relatively high levels of sole child care were grouped using an iterative process of independent analysis, comparison and rechecking. Reasons included mother's and father's employment situation and relative earning power, the absence of acceptable alternative child care, perceptions of societal values, maternal and paternal health, family history and ideological values. Flexibility of paternal employment, or its relative unimportance, and motivation or willingness on the part of the father to share in child care were invariably present. For some, the fact of one or other of their own parents having been emotionally distant or physically absent had led to a determination to do things differently with their own children. Fathers reported that they valued the increased time spent with their child, even if they had not been consciously motivated beforehand. Fathers describe a wide range of reasons for becoming primary caregivers for their infant, and generally experience themselves as being actively involved in that decision. If fathers are to take an increasing role in child care, societal values and financial pressure may need to be addressed.

Maternal family history of hypertension attenuates neonatal pain response

Reduced sensitivity to naturally occurring and laboratory pain stimuli has been observed in individuals with hypertension, high-normal blood pressure, and a family history of hypertension. The present study sought to extend these findings by examining the relationship between familial history of hypertension and pain responsivity in neonates. Eighty infants had intramuscular (IM) injections of vitamin K performed in the delivery room within 1 h of birth as per institutional practice. Video recordings of the injection procedure were used by trained observers to code infant pain responses using facial grimacing and cry duration. Prior to the birth of the child, the infants’ parents each completed a family blood pressure history survey and these responses were used to identify infants with and without a maternal and paternal family history of hypertension. As compared to infants without a maternal family history of hypertension, infants with a maternal family history of hypertension had significantly shorter crying times, F(1, 74) = 6.96, p = .01, η 2 = .086, and marginally lower facial grimacing scores, F(1, 74) = 2.68, p = .10, η 2 = .035, during vitamin K injection. The presence of attenuated responses to the IM injection in neonates with a maternal family history of hypertension provides important and novel evidence that reduced pain responding in individuals at risk for hypertension is not a learned response style, but rather may arise from prenatal or genetic influences.

A genetic syndrome of chronic renal failure with multiple renal cysts and early onset diabetes

Department of Radiology, University of IowaCollege of Medicine, Iowa City, Iowa, USACASE PRESENTATIONThe patient is a 48-year-old female who was referred fora renal transplant evaluation in 2006. She was firstdiagnosed with kidney disease in her teens afterpresenting with fatigue and general malaise. On referral toa local nephrologist approximately 30 years ago, animaging study was performed demonstrating renal cystsand the patient was diagnosed to have medullary cystickidney disease (MCKD). At the age of 19, the patient wasdiagnosed with type 1 diabetes and insulin therapy wasstarted. Over the next several years, her kidney functiondeclined slowly (Figure 1).On presentation for her transplant evaluation, hermajor symptom was fatigue, which had not changedsubstantially in 30 years. She also had occasional backpain, which was attributed to bleeding within renal cysts.The patient had no history of gout or genitourinary tractanomalies.There was no history of kidney disease, gout, ordiabetes in first-degree relatives. She has two healthybrothers and healthy parents and has no children. There isa paternal family history of diabetes in second-degreerelatives. Her first menses was at age 12 and were regularuntil 3 months before her appointment. The patient hashad no pregnancies or miscarriages.Physical examination revealed a temperature of36.91C, pulse 101, and blood pressure of 128/92mmHg.There was no evidence of dysmorphic features,pre-auricular pits, or tophi. Her oropharynx was withoutlesions and her palatal arch and dentition were normal.Fundoscopic examination was significant for evidenceof copper wiring with early AV nicking, scatteredmicroaneurysms without hemorrhage, and sharp diskmargins. Her neck examination showed no goiter orlymphadenopathy. Cardiovascular examination wasnormal and her lung fields were clear to auscultation.Examination of the abdomen was unrevealing with nohepatosplenomegaly. There were no flank masses ortenderness noted.Laboratory studies at the time of transplant evaluationshowed a creatinine of 2.8mg/100 ml with an estimatedglomerular filtration rate of 19.9ml/min/1.73 m

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children

AimsTo investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM).MethodsThis cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 ± 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed.ResultsAfter adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history × tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels.ConclusionsMaternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.Diabet. Med. 25, 1043–1048 (2008)

The Contribution of Family History to Hearing Loss in an Older Population

Although it has been well established that the prevalence of and severity of hearing loss increase with age, the contribution of familial factors to age-related hearing loss cannot be quantified. This is largely because hearing loss in older people has both genetic and environmental contributions. As environmental factors play an increasing role with age, it is difficult to delineate the separate contribution of genetic factors to age-related hearing loss. In a population-based survey of hearing loss in a representative older Australian community, we attempted to overcome this using logistic regression analysis, accounting for known factors associated with hearing loss including age, sex, noise exposure at work, diabetes, and current smoking. We tested hearing thresholds using pure tone audiometry and used a forced choice questionnaire to determine the nature of family history in a population of individuals aged 50 yrs or older in a defined region, west of Sydney, Australia (N = 2669). We compared the characteristics of participants with and without family history of hearing loss. Of those reporting a positive family history, we compared subgroups for age, gender and severity of hearing loss, and trends by the severity of hearing loss. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence intervals (CIs) that compared the chances of having hearing loss in participants with and without family history, after adjusting for other factors known associated with hearing loss. Our findings indicate that family history was most strongly associated with moderate to severe age-related hearing loss. We found a strong association between maternal family history of hearing loss and moderate to severe hearing loss in women (adjusted OR 3.0; 95% CI 1.6-5.6 in women with without a maternal history). Paternal family history of hearing loss was also significantly, though less strongly, associated with moderate-severe hearing loss in men (adjusted OR 2.0; CI 1.01-3.9 in men with than without a paternal history). Findings from this study are important in the identification of individuals whose auditory system may be genetically susceptible to aging and environmental insult. Genetic counseling may assist in ameliorating the effects of hearing loss.

P2-008: Regional gray matter brain volume differences in individuals with a maternal versus paternal family history of Alzheimer's disease

P2-008: Regional gray matter brain volume differences in individuals with a maternal versus paternal family history of Alzheimer's disease

UNIPARENTAL DISOMY OF CHROMOSOME 1 CAUSING CONCURRENT CHARCOT-MARIE-TOOTH AND GAUCHER DISEASE TYPE 3

Uniparental disomy (UPD) can be the cause of atypical disease manifestations in patients with Mendelian disorders. Consideration of this disease mechanism proved essential in our evaluation of a 3-year-old boy, referred to the NIH Clinical Center for further evaluation of Gaucher disease (GD). ### Case report. The patient was born at term to non-consanguineous parents with a paternal family history of autosomal dominant Charcot-Marie-Tooth disease type I (CMT1). His medical history included moderate sensorineural hearing loss, Wolff-Parkinson-White arrhythmia, bicuspid aortic valve, and motor delay, ambulating at 26 months. At 17 months, hepatosplenomegaly was noted and a bone marrow biopsy led to the diagnosis of type 3 GD. Molecular analysis revealed homozygosity for the NM_000157.2:c.1448T>C (L444P) mutation in the glucocerebrosidase gene ( GBA ). He began enzyme replacement therapy (Imiglucerase, 120 U/kg biweekly), with significant resolution of his organomegaly. On examination, he had mild hepatosplenomegaly, bilateral pes cavus, externally rotated hips, genu valgus, hammertoes, decreased muscle tone, and mild foot drop. Reflexes were depressed in the upper extremities and absent in knees and ankles. Ophthalmologic evaluation revealed nystagmus, dysconjugate gaze, slowed, hypometric horizontal saccades, and decreased pupillary constriction (Adie-like). Nerve conduction studies were 13 …