Unaffected Parents Of Children Research Articles

Identifying Needs, Challenges, and Benefits Among Adults and Parents of Children With Hirschsprung Disease.

Adults with Hirschsprung disease (HD), unaffected parents of children with HD, and affected adults with an affected child completed a cross-sectional survey with open-ended questions about greatest needs at diagnosis and at current time, greatest challenges encountered, and any benefits of having HD or having a child with HD. In the 297 respondents, information and good medical care were common needs at diagnosis and at the time of survey, but the information needed evolved with time. Managing ongoing symptoms was a frequently cited need and challenge, along with managing medical care and the social and emotional impact of HD. Perceived benefits included empathy for others and new perspectives on life. The needs and challenges identified in this study can guide healthcare providers in discussions with families. Provision of information, recommendations, and referrals based on each individual family's needs can support families with HD throughout the lifecycle and facilitate adaptation.

Health Outcomes of Parents of Children with Chronic Illness: A Systematic Review and Meta-Analysis

To assess health outcomes of parents caring for children with chronic illnesses compared with parents of healthy children. We searched OvidSP MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, EMBASE, and EBSCOHost CINAHL through September 2019. Included were English-language studies reporting health conditions or mortality of parents of affected children compared with healthy controls. Of 12 181 screened publications, 26 met inclusion criteria. Eight studies reported on anxiety, 23 on depression, 1 on mortality, and 1 on cardiovascular disease. Parents of chronically ill children had greater anxiety (standardized mean difference 0.42; 95% CI 0.24-0.60; P<.001) and depression scores (standardized mean difference 0.35; 95% CI 0.26-0.45; P<.001) than parents of healthy children. Thirty-five percent of parents of affected children met cut-offs for clinical depression, compared with 19% in the control (relative risk 1.75; 95% CI 1.55-1.97). Fifty-seven percent of such parents met cut-offs for anxiety, compared with 38% in the control (relative risk 1.40; 95% CI 1.18-1.67). One study of mothers of children with congenital anomalies reported a greater mortality risk than a comparison (adjusted hazard ratio 1.22; 95% CI 1.15-1.29), and another reported that these mothers experience an increased risk of cardiovascular disease (adjusted hazard ratio 1.15; 95% CI 1.07-1.23). Parents of chronically ill children experience poorer mental health (more anxiety and depression), and mothers of those with congenital anomalies may have greater risk of cardiovascular disease and mortality than parents of unaffected children. Our findings suggest a need for targeted interventions to attenuate adverse parental caregiver health outcomes. PROSPERO CRD42018094657 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=94657).

Attention as neurocognitive endophenotype of ADHD across the life span: a family study.

Endophenotypes mediate pathways between genetic variations and the psychiatric phenotype, or share genetic risk with the psychiatric phenotype. Identifying endophenotypes is an important step to unravel disease pathways underlying complex psychiatric phenotypes such as ADHD. Potential viable endophenotypes for ADHD across the lifespan are neurocognitive measures of basic attention functions, such as sustained attention, and executive attention functions (EF), such as inhibition. The present study evaluated the endophenotype criteria of familiality and state-independency for measures of basic attention and EF in affected- and unaffected parents of children with ADHD (N = 139), and typically developing children (N = 60). In addition, the added value of neurocognitive measures relative to questionnaire data in genetically informed designs was explored by comparing the intergenerational transmission of neurocognitive measures to those of ADHD symptom scores. Results revealed small-to-medium-sized familial effects of ADHD for reaction time measures of EF components and state-independency given familial effects. Parent-child correlations as estimates of intergenerational transmission of those neurocognitive measures were not higher than those of behavioral ADHD symptom ratings. Taken together, our results argue against neurocognitive measures as pivotal endophenotypes for ADHD across the lifespan. If studied as neurocognitive endophenotypes of ADHD in adults, reaction time measures of executive-rather than basic attention function-seem to be more sensitive.

Do Unaffected Parents of Children with Orofacial Clefts have Decreased Facial Integration Compared to Controls?

Orofacial clefts are the most common congenital craniofacial anomaly affecting humans. Non‐syndromic clefts may result from decreased integration of the palate during fetal facial growth. This study will investigate whether this pattern is detectable in individuals who do not have a cleft, but do have a child with an orofacial cleft (and therefore carry genetic risk factors for clefting). In order to examine this, we hypothesize that 1) facial shape differences exist between unaffected parents of children with clefts (cases) compared to adults with no history of clefting (controls), and 2) cases will have lower facial integration values compared to controls.For this study, 3D facial scans were obtained from the University of Pittsburgh Center for Craniofacial and Dental Genetics (CCDG). 34 landmarks were placed on n=230 case faces of unaffected parents from the Pitt Orofacial Cleft Study and n=490 control faces from the Pitt 3D Facial Norms Study. Landmarks were aligned using Generalized Procrustes Analysis (GPA) and geometric morphometrics were used for quantifying facial phenotypes. Facial shape differences as a function of age were removed prior to all analyses using linear regression. Canonical Variate Analysis (CVA) was employed to examine shape differences in three different subsets of facial landmarks: a midfacial nose and mouth dataset, a lower facial mouth and jaw dataset and a third dataset consisting of the nose and jaw. Two Block Partial Least Squares analysis (2B PLS) was used to measure the strength of integration by comparing RV coefficients between the case and control populations.Results from the CVA identify significant differences in facial morphology, including jaw width, chin projection, nasal height and mouth width, between cases and controls across all datasets (nose/mouth midfacial set p&lt;0.001, mouth/jaw lower facial set p&lt;0.001, and nose/jaw dataset p=0.028). 2B PLS results, however, showed overall equivalent or higher integration levels in case faces compared to the controls. When comparing levels of integration within the midface (nose and mouth dataset), case samples demonstrate significant (p&lt;0.001) overall higher integration levels (RV=0.352) compared to control samples (RV=0.301). This pattern is also seen within the nose and jaw dataset, with cases (RV=0.614) showing increased integration compared to controls (RV=0.554). Interestingly, integration levels within the lower facial mouth and jaw dataset were nearly identical in both case samples (RV=0.444) and controls (RV=0.447).While facial shape differences exist between unaffected cleft relatives and controls with no family history of clefting, integration values were actually higher in case samples compared to control samples. This indicates that integration in facial soft tissue structures may not serve as a good indicator of cleft risk. Future studies will examine skeletal structures (such as the maxilla and mandible) to test if differences in integration are quantifiable in the facial skeleton only.Support or Funding InformationNIDCR: R01‐DE016148, U01‐DE020078This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Mid-Life Symptoms of Alcoholism on the Health and Wellbeing of Aging Parents of Adults with Disabilities

ABSTRACTThe study examined the effect of adult children’s disability on parents’ physical health in later life and the extent to which parents’ symptoms of alcoholism in mid-life moderates the link between children’s disability and later life parental health. Analyses are based on data from the Wisconsin Longitudinal Study. The analytic sample included parents of children with developmental disabilities (n = 145) or mental health problems (n = 200) and 2,432 parents of unaffected children. The results showed that the negative health consequences in later life of having a child with a developmental disability were greater for those who showed more symptoms of alcoholism in mid-life. However, symptoms of alcoholism in mid-life did not significantly moderate the impact of an adult child’s mental health problems on parents’ later life physical health. The findings suggest a potential area where gerontological social workers could intervene, given the negative impact of symptoms of alcoholism on the health of aging parents of children with a disability who may be significantly more susceptible to the negative health impacts of alcohol compared to their younger counterparts.

Expanding the cleft phenotype: the dental characteristics of unaffected parents of Australian children with non‐syndromic cleft lip and palate

The aetiology of isolated clefts of the lip and/or palate remains obscure. Unaffected family members are treated as if their genetic risks are equivalent and low. Given the number of genes associated with both clefting and dental anomalies, the hypothesis that such anomalies contribute to the cleft phenotype should be explored. To describe the dental characteristics of parents of children with non-syndromic cleft lip ± palate. Unaffected parents of Australian children with a cleft of the lip ± palate underwent dental examination including radiographs, photographs, and impressions. Dental anomalies were identified. Data were available on 101 parents (49 males, 52 females). Fifty-one participants had at least one dental anomaly. Twelve (11.8%) individuals had congenital absence of teeth, with seven missing multiple teeth. The tooth most commonly missing was the upper right lateral incisor. Five subjects (4.9%) had microdontia (upper lateral incisor most commonly affected). Four subjects (4.0%) had supernumerary teeth. Enamel defects were present in 27 (26.7%) cases with the incisors (46.8%) followed by premolars (24.2%) most affected. This study supports previous work suggesting that 'unaffected' parents of children with clefts of the lip ± palate may present with dental anomalies.

Evaluation of terminology used to describe disorders of sex development

Objective The terminology used to describe abnormalities of sex determination and sex differentiation was revised in 2006. It was anticipated that new terms, such as ‘disorders of sex development’ (DSD), would improve communication between health professionals, aid parental understanding and be acceptable to affected individuals. The purpose of this study was to evaluate the success of the new terminology. Subjects and methods Using a questionnaire, we evaluated the acceptance of these new terms by parents of children with a DSD ( n = 19), health professionals ( n = 15) and parents of unaffected children ( n = 25). Results Comparing the term ‘DSD’ to ‘intersex’, overall 86.4% of participants preferred the term ‘DSD’, and parents of a child with a DSD had an even higher preference (94.7%). Parents of an affected child considered the new term to improve their understanding of their child’s condition (83.3%), and to aid explanation by parent to affected child (82.4%) and to wider family and friends (84.2%). Health professionals preferred the genotype-based terms, whereas parents considered these terms confusing. Overall, 59.3% of participants agreed DSD was an acceptable new term. Conclusions There was broad support for the new terminology by parents and health professionals. The description ‘disorder of sex development’ may be helpful to parents at the time when it is not possible to assign gender, after which aetiologically based diagnoses should be used where possible.

Abstract 1327: Study the effect of IGFBP5 in human fibroblast cells

Abstract Retinoblastoma (Rb) is a rapidly developing cancer which develops in the cells of the retina, the light detecting tissue of the eye. It is the most common primary ocular malignancy (eye cancer) of childhood. There are both hereditary and sporadic forms of retinoblastoma. The hereditary form of retinoblastoma is associated with a germ line mutation in one of the RB genes and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. These second tumors often occur in patients treated by radiation therapy. In the previous study, an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb was observed. By use of the prediction analysis for microarrays (PAM) and principal component analysis (PCA), 42 significantly differential expressed genes were selected and identified as radiosensitive genes. Therefore, one of these 42 genes, IGFBP5 (insulin-like growth factor binding protein 5) was chosen to further investigate the role in radiosensitivity in fibroblast cells. IGFBP5 was overexpressed or knocked down in HS68 (the human foreskin fibroblast) cells. The cells were irradiated with γ -ray, and then counted and seeded into the plates for colony formation assays. According to the results, IGFBP5-ovexpressed cells seemed to be more resistant to radiation. Also, IGFBP5 knocked down cells might be more sensitive to radiation under low dose of radiation. In summary, these results suggested that IGFBP5 may play a role in radiosensitivity in human fibroblast cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1327.

Abnormal Gene Expression Profiles in Unaffected Parents of Patients with Hereditary-Type Retinoblastoma

The hereditary form of retinoblastoma (Rb) is associated with a germ line mutation in one RB allele and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. In an earlier study, we observed an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb. In at least four of these five families, there was no family history of Rb, indicating a new germ line mutation. We hypothesize that the increased parental cell sensitivity to radiation may reflect the presence of an as yet unrecognized genetic abnormality occurring in one or both parents of children with Rb. In the present study, we use DNA microarray technology to determine whether differences in gene expression profiles occurred in the unaffected parents of patients with hereditary Rb relative to normal individuals. Microarray analyses were validated by quantitative reverse transcription-PCR measurements. A distinct difference was observed in the patterns of gene expression between unaffected Rb parents and normal controls. By use of the prediction analysis for microarrays and principal component analysis methodologies, significant differences between the two groups were identified when as few as nine genes were analyzed. Further study of this phenomenon may offer a new insight into the genetic mechanisms of Rb and perhaps more broadly in cancer biology.

Parental craniofacial morphology in cleft lip with or without cleft palate as determined by cephalometry: a meta‐analysis

To integrate findings from previous cephalometric studies comparing the craniofacial complex of unaffected parents with cleft lip with or without cleft palate (CL/P) children to controls with no history of the disease. Meta-analysis of case-control cephalometric data. Studies were selected if the unaffected parents of children with CL/P were included and were not combined with parents of children with isolated CP; quantitative data were obtained through cephalometry; the cephalometric variables used were not unique to a study; a case-control design was used; and the means and standard deviations for all variables were reported or could be calculated for both the experimental and the control group. Using raw data obtained from nine studies, mean weighted effect sizes with 95% confidence intervals were calculated for 28 cephalometric variables (mothers and fathers combined) or 18 variables (mothers and fathers separately). Heterogeneity statistics for the effect sizes were also calculated. In general, unaffected parents of children with CL/P possessed significantly wider interorbital, nasal cavity and upper facial dimensions, narrower cranial vaults, longer cranial bases, longer and more protrusive mandibles, shorter upper faces and longer lower faces compared with controls. Increased width of the nasal cavity was the most robust finding. Significant effect size heterogeneity was observed in roughly half of the variables examined. Unaffected parents of children with CL/P are characterized by a suite of consistent, yet subtle, craniofacial differences, which could indicate an underlying genetic liability.

ORAL MUCOSAL MICROVASCULAR NETWORK ABNORMALITIES INDE NOVOMUTATION ACHONDROPLASIA

Approximately 90% of achondroplasia (ACH) cases are the result of a de novo mutation, with no phenotypical markers for the unaffected ACH parents being known to date. Here, the hypothesis of the presence of an oral mucosal microvascular abnormality in ACH children and unaffected ACH parents was tested. Two-dimensional vascular network geometry was analyzed in 15 children with sporadic ACH, 30 unaffected parents of children with typical ACH phenotype, and 45 control subjects, using high-resolution photographs of the lower gingival and vestibular oral mucosa. The vascular networks of ACH patients and ACH parents exhibited higher D(1–46) (P ≤ 0.013) and D(1–15) (P ≤ 0.0032) fractal dimensions, higher minimum-path dimension (P ≤ 0.0013), higher relative Lempel-Ziv (L-Z) complexity (P &lt; 0.0001), and lower vessel-free area size (P &lt; 0.00001) than controls. A vessel-free area size ≤ 56,832 μm2and L-Z complexity &gt; 0.62 showed 100%-sensitivity and 100%-specificity in identifying unaffected ACH parents. These findings indicate (1) how complexity measures can be used to discover biological differences not demonstrable with traditional measures, and (2) the presence of a previously unrecognized microvascular network abnormality in both ACH patients and unaffected parents of children with de novo mutation ACH.

Unexpected sensitivity to radiation of fibroblasts from unaffected parents of children with hereditary retinoblastoma.

The response to ionizing radiation was examined in diploid skin fibroblasts derived from 5 patients with hereditary type retinoblastoma as well as their parents. Unexpected sensitivity to cell killing, as measured by clonogenic survival, as well as enhanced radiation-induced G(1) arrest were observed in at least 1 parental fibroblast strain in all 5 families. In all cases, parental strains were equally or more radiosensitive than the probands. The mutation of the retinoblastoma gene (RB) determined in 4 of 5 probands was either absent from the parental cells, as expected from the negative family histories, or identical, in 1 father who was a known carrier. In the fifth family, the family history was negative for retinoblastoma. We hypothesize that the increased parental cell sensitivity to radiation suggests the presence of an as yet unrecognized genetic event occurring in 1 or both parents of children with retinoblastoma. Whether it increases mutability of the RB locus or other loci or interacts with RB is conjectural.

A High-Risk Pilot Study of the Children of Adults with Social Phobia

Children of patients with social phobia were studied to estimate their rates of psychiatric disorder. Twenty-six social-phobic outpatients who had at least one child between the ages of 4 and 18 years participated in the study. Information was collected from parents on all 47 children and from the children between 12 and 18 years of age. Diagnoses in the children were made based on DSM-III-R and were done by a best-estimate method, using parent and child reports from a modified Anxiety Disorders Interview Schedule for Children, the Survey Diagnostic Instrument, the Current Self-Report Childhood Inhibition Scale, and the Alcohol Dependence Survey. Of the 47 children, 49% had at least one lifetime anxiety disorder diagnosis. The most common diagnoses were overanxious disorder (30%), social phobia (23%), and separation anxiety disorder (19%). Sixty-five percent had more than one anxiety disorder diagnosis. Lifetime major depression was found, in 8.5% of the children. Parents whose children met criteria for an anxiety disorder had a greater mean number of comorbid diagnoses than did the parents of unaffected children. This pilot study suggests that children of social-phobic parents may have increased rates of psychiatric disorder. Further studies incorporating a control group are needed.

Fish odour syndrome: verification of carrier detection test.

An oral trimethylamine challenge test has been used to confirm the heterozygous status of patients with 'fish-odour syndrome'. By measuring the percentage of total urinary trimethylamine-related material excreted as the N-oxide, no discrimination could be made between obligate heterozygotes (parents of 'fish-odour syndrome' patients) (n = 15; 96 +/- 2%, range 92-98%) and control individuals (parents of unaffected children) (n = 16; 96 +/- 2%, range 93-99%) on a normal diet. However, after ingesting a trimethylamine load (600 mg base) the obligate heterozygotes were clearly distinguishable (76 +/- 3%, range 71-79%) from controls (95 +/- 2%, range 91-99%) (t-test; p <0.001). One of a hundred apparently normal volunteers who were subsequently challenged with trimethylamine had a N-oxidation capacity which fell within the range found among the obligate heterozygotes.