Kctd13 deletion reduces synaptic transmission via increased RhoA.

Copy-number variants of chromosome 16 region 16p11.2 are linked to neuropsychiatric disorders and are among the most prevalent in autism spectrum disorders. Of many 16p11.2 genes, Kctd13 has been implicated as a major driver of neurodevelopmental phenotypes. The function of KCTD13 in the mammalian brain, however, remains unknown. Here we delete the Kctd13 gene in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of Ras homolog gene family, member A (RhoA), a KCTD13/CUL3 ubiquitin ligase substrate, and is reversed by RhoA inhibition, suggesting increased RhoA as an important mechanism. In contrast to a previous knockdown study, deletion of Kctd13 or kctd13 does not increase brain size or neurogenesis in mice or zebrafish, respectively. These findings implicate Kctd13 in the regulation of neuronal function relevant to neuropsychiatric disorders and clarify the role of Kctd13 in neurogenesis and brain size. Our data also reveal a potential role for RhoA as a therapeutic target in disorders associated with KCTD13 deletion.

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.2 impact regional brain volume, white matter integrity, and early sensory responses in auditory cortex. Here, we test the hypothesis that abnormal cortical neurophysiology is present when genes in the 16p11.2 region are haploinsufficient, and in humans that this in turn may account for behavioral deficits specific to deletion carriers. We examine sensorimotor cortical network activity in males and females with 16p11.2 deletions compared with both typically developing individuals, and those with duplications of 16p11.2, using magnetoencephalographic imaging during preparation of overt speech or hand movements in tasks designed to be easy for all participants. In deletion carriers, modulation of beta oscillations (12-30 Hz) were increased during both movement types over effector-specific regions of motor cortices compared with typically developing individuals or duplication carriers, with no task-related performance differences between cohorts, even when corrected for their own cognitive and sensorimotor deficits. Reduced left hemispheric language specialization was observed in deletion carriers but not in duplication carriers. Neural activity over sensorimotor cortices in deletion carriers was linearly related to clinical measures of speech and motor impairment. These findings link insufficient copy number repeats at 16p11.2 to excessive neural activity (e.g., increased beta oscillations) in motor cortical networks for speech and hand motor control. These results have significant implications for understanding the neural basis of autism and related neurodevelopmental disorders.SIGNIFICANCE STATEMENT The recurrent ∼600 kb deletion at 16p11.2 (BP4-BP5) is one of the most common genetic etiologies of ASD and, more generally, of neurodevelopmental disorders. Here, we use high-resolution magnetoencephalographic imaging (MEG-I) to define with millisecond precision the underlying neurophysiological signature of motor impairments for individuals with 16p11.2 deletions. We identify significant increases in beta (12-30 Hz) suppression in sensorimotor cortices related to performance during speech and hand movement tasks. These findings not only provide a neurophysiological phenotype for the clinical presentation of this genetic deletion, but also guide our understanding of how genetic variation encodes for neural oscillatory dynamics.

Family experiences and attitudes about receiving the diagnosis of sex chromosome aneuploidy in a child.

The most common sex chromosome aneuploidies (SCA) (47, XXY; 47, XYY; 47, XXX) frequently result in a milder phenotype than autosomal aneuploidies. Nevertheless, these conditions are highly variable and more symptomatic phenotypes may require significant clinical involvement, including specialty care. While historically most individuals with mild phenotypes remained undiagnosed during their lifetime, the increasing use of genetic testing in clinical care has increased the prenatal and postnatal diagnosis of SCAs. These genetic tests are frequently ordered by nongenetic providers who are also responsible for delivering the diagnosis. We surveyed parents of children (n = 308) to evaluate their experience of receiving a diagnosis and their support needs. The majority (73.3%) received the diagnosis from a nongenetic medical provider. Following a prenatal diagnosis parents reported experiencing depression, anxiety, and less optimism than those receiving a postnatal diagnosis. Few parents reported receiving materials explaining their child's condition that they found to be up-to-date, accurate, and unbiased. The frequently negative reported experiences of parents at time of diagnosis suggests more educational opportunities should be provided for nongenetic providers in order to become more informed about these conditions and communicate the diagnosis in a way parents experience as supportive.

Incontinence and psychological symptoms in Phelan-McDermid syndrome.

AIMS: Phelan-McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped-repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD. METHODS: Forty-one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4-55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills. RESULTS: Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty-two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher "anxiety/depression" subscale scores. Toileting skills were more developed in adults than in children. Sixty-eight percent had further physical disabilities. CONCLUSIONS: Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended.

Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome.

BACKGROUND: The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype-phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. METHOD: We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland-II Scale and the Child Behaviour Checklist, respectively. Socio-economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. RESULTS: Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non-verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland-II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio-economic status may contribute to overall patient development. CONCLUSION: Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio-economic conditions may influence cognitive development.

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome.

18p deletion syndrome is a rare chromosomal disease caused by deletion of the short arm of chromosome 18. By using cytogenetic and SNP array analysis, we identified a girl with 18p deletion syndrome exhibiting craniofacial anomalies, intellectual disability, and short stature. G-banding analysis of metaphase cells revealed an abnormal karyotype 46,XX,del(18)(p10). Further, SNP array detected a 15.3-Mb deletion at 18p11.21p11.32 (chr18:12842-15375878) including 61 OMIM genes. Genotype-phenotype correlation analysis showed that clinical manifestations of the patient were correlated with LAMA1, TWSG1, and GNAL deletions. Her neuropsychological assessment test demonstrated delay in most cognitive functions including impaired mathematics, linguistic skills, visual motor perception, respond speed, and executive function. Meanwhile, her integrated visual and auditory continuous performance test (IVA-CPT) indicated a severe comprehensive attention deficit. At age 7 and 1/12 years, her height was 110.8 cm (-2.5 SD height for age). Growth hormone (GH) treatment was initiated. After 27 months treatment, her height was increased to 129.6 cm (-1.0 SD height for age) at 9 and 4/12 years, indicating an effective response to GH treatment.

UK families with children with rare chromosome disorders: Changing experiences of diagnosis and counselling (2003-2013).

The latest United Kingdom (UK) strategy for rare diseases emphasises the need to empower affected populations to improve diagnosis, intervention, and coordination of care. Families who have a child with a rare chromosome disorder (RCD) are a challenging group to include. We report the findings of 2 large-scale surveys, undertaken by the UK RCD Support Group Unique, of these families' experiences over a 10-year period. Seven stages of the patient journey were examined. From pre-testing, through diagnosis, genetics consultation, clinical follow-up and peer support. Overall, 1158 families replied; 36.4% response rate (2003) and 53.6% (2013). Analysis of responses identifies significant differences (P < .001) over time with a decrease in results reported face to face (76%-62%), doubling by telephone (12%-22%), improved explanation of chromosome disorder (57%-75%), and increased signposting to peer support group (34%-62%). However, conduct of the consultation raises a number of important questions. Overall, 28 aspects of the patient journey are recognised as requiring improvement; only 12/28 are currently incorporated in UK service specifications. Involvement of RCD families has identified key service improvements. This approach can empower those affected by such extremely rare disorders, and also enable professionals to design improved services in partnership with "expert families." Further surveys are planned.

Phelan-McDermid syndrome in adult patient with atypical bipolar psychosis repeatedly triggered by febrility.

Phelan-McDermid syndrome (PMD) is a rare genetic condition with only a few cases describing patients diagnosed as adults. We describe a long diagnostic odyssey of a 30-year-old woman who was diagnosed with Phelan-McDermid syndrom. Array comparative genomic hybridization analysis confirmed a 22q13.33 deletion, encompassing exon 9-23 of the SHANK3 gene and exon 1 of the ACR gene. We provide an uncommon feature of the disease, where psychotic alteration is repeatedly triggered by the same physical factor in our patient - mild fever episodes.

Study protocol for The Emory 3q29 Project: evaluation of neurodevelopmental, psychiatric, and medical symptoms in 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is caused by a recurrent hemizygous 1.6 Mb deletion on the long arm of chromosome 3. The syndrome is rare (1 in 30,000 individuals) and is associated with mild to moderate intellectual disability, increased risk for autism and anxiety, and a 40-fold increased risk for schizophrenia, along with a host of physical manifestations. However, the disorder is poorly characterized, the range of manifestations is not well described, and the underlying molecular mechanism is not understood. We designed the Emory 3q29 Project to document the range of neurodevelopmental and psychiatric manifestations associated with 3q29 deletion syndrome. We will also create a biobank of samples from our 3q29 deletion carriers for mechanistic studies, which will be a publicly-available resource for qualified investigators. The ultimate goals of our study are three-fold: first, to improve management and treatment of 3q29 deletion syndrome. Second, to uncover the molecular mechanism of the disorder. Third, to enable cross-disorder comparison with other rare genetic syndromes associated with neuropsychiatric phenotypes. METHODS: We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR). DISCUSSION: The study of 3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.

Implementing Group Prenatal Counseling for Expanded Noninvasive Screening Options.

Recently, practices have begun integrating cell-free DNA-based noninvasive prenatal screening as a screening option for a variety of genetic conditions. According to the National Society of Genetic Counselors, the integration of cfDNA screening into clinical prenatal practice may "significantly shift the paradigm of prenatal testing and screening for all women." The purpose of this study was to determine whether group information sessions can feasibly serve as an alternative to extended one-on-one genetic counseling for the increasing number of women making decisions about prenatal testing and screening. This study assessed the effect of group genetic information sessions coupled with abbreviated counseling on pregnant women's knowledge about and attitudes toward prenatal testing and screening.

Investigating Pregnancy Outcomes After Abnormal Cell-Free DNA Test Results.

Cell-free DNA (cfDNA) testing has increased sensitivity and specificity compared to other prenatal screening methods, but invasive diagnostic testing (IDT) is recommended for confirmation. We performed a retrospective chart review of 39 women with abnormal cfDNA results between March 2012 and September 2015 at an urban academic hospital to evaluate patient choice and pregnancy outcomes. We analyzed data using descriptive statistics, Fisher's exact tests, and Wilcoxon rank-sum tests. Median maternal age was 36.0 years [interquartile range (IQR) 31, 39]; 64.1% of women (25/39) were advanced maternal age and 69.2% (27/39) had abnormal ultrasounds. Median gestational age at time of cfDNA testing was 18 3/7 weeks [IQR 12 2/7, 20 5/7]. cfDNA results included trisomy 21 (89.7%, 35/39), trisomy 18 (7.7%, 3/39), and both trisomy 21/monosomy X (2.6%, 1/39). Of 39 women, 22 (56.4%) continued and 10 (25.6%) terminated the pregnancy; six (15.4%) had fetal demises, and one was lost to follow-up. Of women continuing their pregnancies, 54.6% (12/22) declined further genetic counseling, and 77.3% (17/22) declined IDT. Only 14 women pursued IDT; not pursuing IDT was associated with continuing the pregnancy (Fisher's exact test, p = .001). All women terminating their pregnancy (90.0%, 9/10) pursued IDT or had major anomalies on ultrasound, suggesting that women considering termination undergo more confirmatory tests or already have high suspicion for an abnormal pregnancy.

Parental hopes, interventions, and survival of neonates with trisomy 13 and trisomy 18.

Trisomy 13 and 18 are life-limiting conditions for which a palliative approach is frequently recommended. The objective of this study was to examine parental goals/decisions, the length of life of their child and factors associated with survival. Parents of children who lived with trisomy 13 or 18 that were part of English-speaking social networks were invited to participate in a questionnaire study. Participants answered questions about their hopes/goals, decisions regarding neonatal interventions, and the duration of their children's lives. The participants were 332 parents who answered questions about their 272 children (87% response rate based on site visits; 67% on invitations sent). When parents were asked about their hope after the diagnosis, the main themes invoked by parents were the following: meet their child alive (80% of parents with a prenatal diagnosis), spend some time as a family (72%), bring their child home (52%), and give their child a good life (66%). Parents wanted to give them a chance, but also reported their fears were medical complexity, pain and/or life in the hospital (61%). Healthcare providers recommended comfort care at birth to all parents. Life-sustaining interventions "as for any other child" was chosen as a plan of care by 25% of parents. Of the 216 children with full trisomy, 69% were discharged home after birth and 40% lived >1 y. The presence of a prenatal diagnosis was the strongest independent factor negatively associated with longevity: 36% of children with a prenatal diagnosis lived <24 hr and 47% were discharged home compared to 1% and 87%, respectively for children with a postnatal diagnosis (P < 0.01). Male gender, low-birth weight, and cardiac and/or cerebral anomaly were also associated with decreased survival (P < 0.05). After a prenatal diagnosis, palliative care at birth consisted of limited interventions, whereas after a postnatal diagnosis (median age of 6 days) it consisted of various interventions, including oxygen, ventilation, tube feeding and intravenous fluids, complicating the analysis. In conclusion, the goals of parents of children with trisomy 13 or 18 were to meet their child, be discharged home and be a family. Having a postnatal diagnosis was the independent factor most associated with these goals. Children with a postnatal diagnosis were treated "as any other children" until the diagnosis, which may give them a survival advantage, independent of palliative care. Rigorous transparency regarding specific interventions and outcomes may help personalize care for these children. © 2016 Wiley Periodicals, Inc.

What results to disclose, when, and who decides? Healthcare professionals' views on prenatal chromosomal microarray analysis.

OBJECTIVES: This study explored the views of healthcare professionals (HCPs) in the UK about what information should be disclosed, when; and whether women/parents should be given a choice as to what they wish to know. METHODS: Q-methodology was used to assess the views of 40 HCPs (genetic HCPs, fetal medicine experts, lab-scientists). RESULTS: Most participants agreed that variants of unknown clinical significance should not be disclosed. Participants were divided between those who considered variants of uncertain clinical significance helpful for parents and clinicians, and those who considered them harmful. Although recognising the potential disadvantages of disclosing risks for adult-onset conditions, participants thought it would be difficult to withhold such information once identified. Participants largely supported some parental involvement in determining which results should be returned. Most participants believed that information obtained via CMA testing in pregnancy should either be disclosed during pregnancy, or not at all. CONCLUSION: HCPs taking part in the study largely believed that variants that will inform the management of the pregnancy, or are relevant to other family members, should be reported. Recent UK guidelines, published after this research was completed, reflect these opinions.

Swedish University Students' Opinion Regarding Information About Soft Markers.

The aim of this study was to investigate the opinions of Swedish university students about information regarding soft markers, when observed at second trimester ultrasound screening. A cross-sectional survey, where 85 Swedish university students completed a study specific questionnaire containing eleven hypothetical scenarios, involving various parameters (disease/syndromes/malformations with different characteristics), and location of the markers. Almost all participants indicated that they would wish to be informed, prior to the ultrasound examination, about the assessment and significance of soft markers. However, the number of respondents who requested information about a potential actual finding was considerably less. Several participants wanted to be informed about detected markers associated to serious conditions but not when the marker indicated an increased risk for a treatable disease. Also, the specific location of the marker was of importance to the participants. The majority of respondents wished to be informed about the soft markers if they were observed in the heart or the brain of the foetus, compared to if they were located in the intestine or the skeleton. The students' opinion, in this study, implicate the importance of pre-examination information to enable expectant parents to make informed choice regarding the second trimester ultrasound screening as well as on reciving information of actual findings.

16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.

Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome.

Trisomy 13: Changing Perspectives.

The diagnosis of trisomy 13 has been considered incompatible with life. Trisomy 13 is associated with a pattern of congenital anomalies and mental disabilities that make caring for these infants a challenge for both the family and health care professionals. The clinical management of trisomy 13 varies based on the organ systems involved. The current standard of care has been withholding intensive support and providing comfort care. Recent literature suggests there are improved outcomes in infants who receive intensive care at birth. In addition, case reports evaluating older children with trisomy 13 report that, although there are significant intellectual and psychomotor disabilities, these children do meet developmental milestones such as smiling in response to parents, sitting unassisted, and walking with a walker. This case review will include a discussion of the clinical course of an infant born with mosaic trisomy 13 where the parents requested intensive care.

"How should I tell my child?" Disclosing the diagnosis of sex chromosome aneuploidies.

To date, the disclosure of a sex chromosome aneuploidy (SCA) diagnosis to an affected individual has not been explored. This study aimed to assess the timing and content revealed to an affected child by his or her parent(s), resources accessed in preparation, parental feelings of preparedness, common parental concerns, and recommendations for disclosure approaches. Two online surveys were created: 1) for parents of a child with a diagnosis and 2) for individuals with a diagnosis. One-hundred thirty-nine parent surveys (XXY n = 68, XXX n = 21, XYY n = 9, other SCAs n = 41) and 67 individual surveys (XXY n = 58, XXX n = 9) were analyzed. Parents most frequently discussed the topics of learning disabilities (47 %) and genetics (45 %) with their child during the initial disclosure. A significantly greater proportion of parent respondents reported feeling prepared vs. unprepared for disclosure, regardless of their child's diagnosis (z-test of proportions, all p's < 0.001). Both prepared and unprepared parents most frequently accessed resources such as websites, support groups, and discussion with the child's physician prior to disclosure, with unprepared parents accessing fewer resources (M = 2.0 ± 1.41) than prepared parents [M = 2. ± 1.56; t(101) =-2.02, p < 0.05]. Common parental concerns included making the conversation age-appropriate, discussing infertility, and possible impact on the child's self-esteem. Both parent and individual respondents endorsed being honest with the child, disclosing the diagnosis early and before puberty, and discussing the diagnosis gradually over time. These results provide recommendations for parents, and suggest benefits from additional resources and supports to alleviate concerns when approaching diagnosis disclosure.

Parental decisions following prenatal diagnosis of chromosomal abnormalities: implications for genetic counseling practice in Japan.

Parental decision-making to terminate or continue a pregnancy was studied after prenatal diagnosis of a chromosome aneuploidy among a sample of patients around the city of Nagoya, Japan. A total of 1,051 amniocentesis cases at 15-18 weeks of gestation were analyzed. Of these, 60 cases of chromosomal anomalies with aneuploidies were diagnosed by conventional cytogenetic analysis. Of the 45 diagnoses of autosomal chromosome aneuploidies, pregnancy was terminated in 93.3 % of the cases. Of the 15 cases diagnosed with sex chromosome aneuploidy, pregnancy was terminated in 46.7 %. Differences in parental decisions with respect to maternal age, gestational week at diagnosis, number of pregnancies per individual and existing number of children were not significant in patients diagnosed either with autosomal or sex chromosome aneuploidy. The findings indicate that when diagnosed with a chromosome aneuploidy in which a severe prognosis was expected, most couples decided to terminate the pregnancy in Japan. Implications of these findings for expanding the profession of genetic counseling are discussed and research recommendations are provided.

A Case Study of Trisomy 13: Balancing Hope and Reality.

BACKGROUND: Trisomy 13, also known as Patau syndrome, occurs in 1/10,000 live births. Trisomy 13 is traditionally considered "lethal" with death as an outcome to be expected quickly. With regard to treatment decisions, families may feel that they are being judged by the medical community and their perception of quality of life. PURPOSE: This case describes an intrauterine growth restricted preterm female presenting with multiple dysmorphic features. METHODS: Using a case description as an example, the use of palliative care and alternative approaches to caregiving with the family of an infant with Trisomy 13 are explored. FINDINGS/RESULTS: A definitive diagnosis of trisomy 13 was made and discussed with the family at day 4 of life. Palliative care was initially used along with life-extending care. IMPLICATIONS FOR PRACTICE: With progression of the disease palliative care comes more to the forefront to help relieve physical and emotional suffering for not only the infant but the family, too. Offering nontraditional opportunities can help create a legacy and allow the families to know that their baby's life had meaning. IMPLICATIONS FOR RESEARCH: Providing caregiver information on the diagnosis and specialized palliative care may improve infant and family outcomes.

Our children are not a diagnosis: the experience of parents who continue their pregnancy after a prenatal diagnosis of trisomy 13 or 18.

Trisomy 13 and trisomy 18 (T13-18) are associated with high rates of perinatal death and with severe disability among survivors. Prenatal diagnosis (PND) may lead many women to terminate their pregnancy but some women choose to continue their pregnancy. We sent 503 invitations to answer a questionnaire to parents who belong to T13 and 18 internet support groups. Using mixed methods, we asked parents about their prenatal experience, their hopes, the life of their affected child, and their family experience. 332 parents answered questions about 272 children; 128 experienced PND. These parents, despite feeling pressure to terminate (61%) and being told that their baby would likely die before birth (94%), chose to continue the pregnancy. Their reasons included: moral beliefs (68%), child-centered reasons (64%), religious beliefs (48%), parent-centered reasons (28%), and practical reasons (6%). At the time of the diagnosis, most of these parents (80%) hoped to meet their child alive. By the time of birth, 25% chose a plan of full interventions. A choice of interventions at birth was associated with fewer major anomalies (P < 0.05). Parents describe "Special" healthcare providers as those who gave balanced and personalized information, respected their choice, and provided support. Parents make decisions to continue a pregnancy and choose a plan of care for their child according to their beliefs and their child's specific medical condition, respectively. Insights from parents' perspective can better enable healthcare providers to counsel and support families.