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Background Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. Methods Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. Results Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. Conclusions Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.

Neuroimmune cells, particularly microglia and astrocytes, play a critical role in neurodevelopment. Neurocognitive delays are common in children with congenital heart disease, but their etiology is poorly understood. Our objective was to determine whether prenatal hypoxemia, at levels common in congenital heart disease, induced neuroimmune activation to better understand the origins of neurobehavioral disorders in congenital heart disease.Eight fetal sheep at gestational age 109 ± 3 days (term ∼145 days) were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 22 ± 2 days under normoxic (n = 4) or hypoxic (n = 4) conditions. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were stained with ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein antibodies to quantify microglia and astrocytes, respectively, in gray and white matter in frontotemporal and cerebellar sections. Microglia were classified into 4 morphologic types based on cell shape. Data were analyzed with 1-way analysis of variance or Fisher exact test, as appropriate.Oxygen delivery was significantly reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min; P .01). Rates of apoptosis were similar in hypoxic, normoxic, and intrauterine control animals in all examined areas. There were also no differences between groups in area occupied by glial fibrillary acidic protein-labeled astrocytes or ionized calcium-binding adaptor molecule 1-labeled microglia in all examined areas. However, round microglia were significantly increased in hypoxic animals compared with normoxic animals (33% vs 6%; P .01) and control animals (33% vs 11%; P .01).Prenatal hypoxemia altered microglial morphology without significant gliosis. Additional studies characterizing these mechanisms may provide insight into the origins of neurobehavioral disabilities in children with congenital heart disease.

Extracorporeal membrane oxygenation is a life-saving intervention, but bleeding complications are frequent. Given that the combination of platelet loss and dysfunction is a major contributor to this acquired bleeding diathesis, efforts to combat these phenomena are of great clinical importance. In this study, we investigated the effects of nitric oxide (NO) added to the sweep gas of an extracorporeal circuit in a neonatal ovine model. Eight lambs (age 9.6 ± 1.9 days) were cannulated via the neck vessels and maintained on a pumpless arteriovenous extracorporeal membrane oxygenation circuit with blood flow restricted to 100 ml/min for 72 hours. All animals were heparinized, and a subset (n = 4) also received NO in the sweep gas at a concentration of 200 ppm. We observed no adverse effects from NO administration, and methemoglobin levels remained unchanged. Platelet counts significantly declined in all animals over the course of the study; however, mean counts were higher in the NO-treated group, and this difference was statistically significant at 24 hours (62 ± 3% vs. 32 ± 7% of baseline, P < 0.01). Likewise, mean plasma levels of beta-thromboglobulin, a marker of platelet activation, were lower in the NO-treated group, and this difference was also significant at the 24 hour time point (9.5 ± 2.2 vs. 19.7 ± 6.5 pg/mL/10 platelets, P < 0.05). We conclude that 200 ppm NO can be safely blended into the oxygenator sweep gas of a low-flow extracorporeal circuit and that it may transiently attenuate platelet consumption and activation.

We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment.Eight mid-gestation fetal sheep were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid-filled environment for 22 ± 2 days under normoxic or hypoxic conditions. Total parenteral nutrition was provided. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were fixed for histopathology. Neurons were quantified in white matter tracts, and the thickness of the external granular layer of the cerebellum was measured to assess neuronal migration. Capillary density and myelination were quantified in white matter. Data were analyzed with unpaired Student t tests or 1-way analysis of variance, as appropriate.Oxygen delivery was reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min, P .01), but umbilical blood flow and caloric delivery were not different between the 2 groups. Compared with normoxic and control animals, hypoxic fetuses had reduced neuronal density and increased external granular layer thickness. Compared with normoxic and control animals, hypoxic fetuses had increased capillary density in white matter. Cortical myelin integrity score was lower in the hypoxic group compared with normoxic and control animals. There was a significant negative correlation between myelin integrity and capillary density.Chronic fetal hypoxia leads to white matter hyper-vascularity, decreased neuronal density, and impaired myelination, similar to the neuropathologic findings observed in children with congenital heart disease. These findings support the hypothesis that fetal hypoxia, even in the setting of normal caloric delivery, impairs neurodevelopment.

Background: We recently developed an EXTrauterine Environment for Neonatal Development (EXTEND) that provides physiologic support for premature lambs. Here, we assess the efficacy of exogenous erythropoietin (EPO) to prevent anemia and transfusions on EXTEND. Materials and Methods: Lambs were cannulated at 0.7 gestation and supported on EXTEND for up to 4 weeks. The lambs were divided into three groups: (1) No EPO, (2) Low EPO (300 U kg–1 per day), and (3) High EPO (800 U kg–1 per day). Daily hematocrit and weekly complete blood count were assessed. Results: The mean percentage change in hematocrit from baseline was significantly different between the groups (No EPO –23.6 ± 7.8% vs. Low EPO –16.6 ± 6.4% vs. High EPO +2.6 ± 6.6%; p = 0.02). This occurred despite a greater median number of blood transfusions in the No EPO group (5 vs. 1 vs. 0; p = 0.02). EPO administration was associated with a higher mean corpuscular volume (MCV; p < 0.01) and reticulocyte count (p = 0.02). The High EPO group was comparable to in utero control fetuses with respect to hematocrit (p = 0.49), MCV (p = 0.24), and reticulocyte count (p = 0.68). Conclusions: EPO (800 U kg–1 per day) prevents anemia, eliminates transfusions, and restores normal red blood cell indices in premature lambs supported by EXTEND.

Background: In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants. Objectives: We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level. Methods: Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105–107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3–4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128–134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured. Results: There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed. Conclusions: Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Background Minimally invasive fetal surgery, or fetoscopy, is an alternative to open fetal surgery to repair common birth defects like myelomeningocele. Although this hysterotomy-sparing approach reduces maternal morbidity, the effects of in utero insufflation on the fetus are poorly understood. Our purpose was to determine the optimal fetal insufflation conditions. Methods Fetal sheep at gestational age 104 to 107 days were studied under insufflation conditions in utero and ex utero. The ex utero fetuses were cannulated via their umbilical vessels into a support device, the EXTra-uterine Environment for Neonatal Development (EXTEND). EXTEND fetuses were exposed to four different insufflation conditions for four hours: untreated carbon dioxide (CO2) (n = 5), warm humidified (whCO2) (n = 4), whCO2 with the umbilical cord exposed (n = 3), and whCO2 without amniotic fluid (skin and cord exposed) (n = 3). Results In utero insufflation led to significant increases in fetal CO2 and reductions in fetal pH. Ex utero insufflation with whCO2 did not lead to changes in fetal blood gas measurements or cerebral perfusion parameters. Insufflation with whCO2 with an exposed umbilical cord led to reduced umbilical blood flow. Conclusions Insufflation with warm humidified CO2 with an amniotic fluid covered umbilical cord is well tolerated by the fetus without significant changes in hemodynamics or cerebral perfusion parameters. Type of study Basic science Level of evidence N/A

Background The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children. Methods A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease. Results Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5–5.9, p = 0.002). Nodule dimension > 2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6–7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p Conclusion Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC. Type of Study Clinical Research, Retrospective Review. Level of Evidence Level IV.

In this model article, we present a protocol for continuous amniotic fluid exchange in rabbits using a novel system to test the effects of growth factor-deficient, artificial amniotic fluid on bowel development. Background: Ideally, the EXTrauterine Environment for Neonatal Development (EXTEND) will provide physiologic support to the extreme premature infant. An important component of that environment is the amniotic fluid. Thus, we developed an animal model to study the growth factors found within amniotic fluid and inform design of a synthetic fluid to optimize fetal development. Methods: We designed a model of amniotic fluid exchange within the pregnant rabbit, continuously removing the natural fluid from around 2 fetuses per doe and replacing it with a physiologic electrolyte solution during the final 100 h of gestation. Two fetuses from the contralateral uterine horn were used as sham-operated controls. Thirty-eight fetuses were analyzed, 19 in each group. We analyzed the fetal growth and bowel development. Results: Ultrasound after 100 h of exchange showed equivalent fluid volumes, p = 0.63. Cultures were negative for bacterial colonization. Final fluid protein concentrations were 11.6% that of control fluid (mean 1,451 ± 224.2 vs. 12,491 ± 849.2 μg/mL). There was no significant difference in fetal growth, with experimental weights 91.4% of control weights, p = 0.07. Fetal bowel weights (90.1%, p = 0.16) and lengths (94.2%, p = 0.49) were also not significantly less compared to controls. There was no significant difference in villous height or crypt depth measurements between the groups, and absorptive capacity of the bowel was not different between groups, p = 0.44. Conclusion: This animal model allows for manipulation of the components of amniotic fluid. Marked reduction of natural amniotic fluid proteins during gestation does not appear to significantly impair fetal growth or bowel development. Further work with this model will assess the importance of amniotic fluid components for normal development to inform design of a synthetic fluid for use during EXTEND.

Psychotic disorders in children are more heterogeneous than is captured by categorical diagnoses. In a new cohort of children and adolescents, we evaluated the relationships among age at onset (AAO), clinical symptoms and developmental impairments. Patients with schizophrenia and other "spectrum" psychotic diagnoses (N = 88; AAO 6-17, mean 12.6) were evaluated with diagnostic interviews, a new clinical scale (Lifetime Dimensions of Psychosis Scale-Child and Adolescent), and neuropsychological and medical evaluations. Key findings were replicated in an adult cohort of 2420 cases, including 127 with retrospective AAO13. Factor and cluster analyses were carried out to identify clinical profiles. Five clinical factors were identified in each cohort: Positive, Bizarre Positive, Negative/Formal Thought Disorder, Depression and Mania. Earlier AAO predicted severity of bizarre positive symptoms in children and of bizarre and other symptoms in adults. Four clinical clusters in the child cohort were characterized by: more severe bizarre positive symptoms (N = 31); negative symptoms (N = 15); premorbid autism spectrum features and developmental delay (N = 12); and depressive symptoms with heterogeneous diagnoses and mild positive/negative symptoms (N = 25). Previous factor-analytic studies of childhood psychosis did not specifically consider bizarre positive symptoms. Here, bizarre positive symptoms emerged as clinical markers of severe, childhood-onset psychosis similar to adult schizophrenia. The four clusters are clinically meaningful and useful for treatment planning and potentially for biological research. Childhood-onset cases are rare and thus difficult to study, but additional, larger cohorts may be useful in dissecting the biological and developmental heterogeneity of psychotic disorders.

Introduction: Fetuses with “high-risk” sacrococcygeal teratoma (SCT) have a mortality rate of 40–50%. While fetal surgery may benefit select fetuses prior to 27 weeks’ gestation, many fetuses die due to consequences of rapid tumor growth after 27 weeks. Here we report our experience applying “preemptive” delivery to fetuses who manifest signs of decompensation between 27 and 32 weeks. Methods: A retrospective review of SCT fetuses delivered between 2010 and 2016 at ≤32 weeks’ gestation was performed. Patients who decompensated prior to 27 weeks and were treated with fetal surgery or neonatal palliation were excluded. Results: Forty-two SCT fetuses were evaluated, and 11 were preemptively delivered in response to impending fetal or maternal decompensation. Nine (81.8%) survived. One death was due to pulmonary hypoplasia in a neonate with significant intra-abdominal tumor burden, and the other was due to in utero tumor rupture. There were no deaths related to prematurity in this cohort. Conclusions: Many fetuses with SCT manifest signs of decompensation between 27 and 32 weeks. In the absence of fetal hydrops prior to 27 weeks or tumor rupture in utero, early delivery is associated with favorable outcomes. Our single-center experience supports a management algorithm change to incorporate “preemptive” delivery for selected cases.

Background/Purpose Neurologic injury remains the most important morbidity of prematurity. Those born at the earliest gestational ages can face a lifetime of major disability. Perinatal insults result in developmental delay, cerebral palsy, and other profound permanent neurologic impairments. The EXTracorporeal Environment for Neonatal Development (EXTEND) aims to transition premature neonates through this sensitive period, but it's impact on neurologic development requires analysis. Methods Fetal sheep were maintained in a fluid-filled environment for up to 28 days. Physiologic parameters were measured continuously; tissues were subsequently fixed and preserved for myelin quantification, glial cell staining, and structural assessment via magnetic resonance. Surviving animals were functionally assessed. Results No evidence of fetal brain ischemia or white matter tract injury associated with the EXTEND system was detected, and the degree of myelination was regionally appropriate and consistent with age matched controls. No evidence of neurologic injury or immaturity was visible on magnetic resonance; animals that transitioned from the system had no persistent neurologic deficits. Conclusions No evidence of major neurologic morbidity was found in animals supported on the EXTEND system, though more work needs to be done in order to verify its safety during critical periods of neurologic development.

In utero hypoxia is a major cause of neonatal morbidity and mortality and predisposes to adult cardiovascular disease. No therapies exist to correct fetal hypoxia. In a new ex utero fetal support system, we tested the hypothesis that hypoxemic support of the fetus impairs myocardial development, whereas normoxic support allows normal myocardial development. Preterm fetal lambs were connected via umbilical vessels to a low-resistance oxygenator and placed in a sterile-fluid environment. Control normoxic fetuses received normal fetal oxygenation, and hypoxemic fetuses received subphysiologic oxygenation. Fetuses with normal in utero development served as normal controls. Hypoxemic fetuses exhibited decreased maximum cardiac output in both ventricles, diastolic function, myocyte and myocyte nuclear size, and increased myocardial capillary density versus control normoxic fetuses. There were no differences between control normoxic fetuses in the fetal support system and normal in utero controls. Chronic fetal hypoxemia resulted in significant abnormalities in myocyte architecture and myocardial capillary density as well as systolic and diastolic cardiac function, whereas control fetuses showed no differences. This ex utero fetal support system has potential to become a significant research tool and novel therapy to correct fetal hypoxia.

Aim of the study Pediatric surgery trainees at our program are allowed to perform unsupervised laparoscopic appendectomies during their last year of training to promote independent operative decision-making skills. We reviewed the outcomes of laparoscopic appendectomies done by senior trainees without supervision and compared them to experienced pediatric surgeons. Methods We reviewed 500 laparoscopic appendectomies performed without supervision by the last 10 pediatric surgery trainees during their last year of training (first 50 cases of each trainee). We compared the outcomes of those 500 cases to the outcomes of 200 laparoscopic appendectomies performed by eight experienced pediatric surgeons (last 25 cases of each surgeon). Data are expressed as mean (SD), unless otherwise indicated. A P value of ≤ 0.05 was regarded as significant. Main results Median age in the “trainees” and “surgeons” groups was 11 (range 2–22) and 12 (2–20) years, respectively (P = 0.35). The proportion of perforated appendicitis was similar: 98/500 (19.6%) in the trainees group and 42/200 (21%) in the surgeons group, respectively (P = 0.75). Mean operative time was 41 (SD 14.5) min in the trainees group vs. 39 (SD 16.1) min in the surgeons group (P = 0.05). Minor intraoperative complications occurred in 3/500 (0.6%) cases in the trainees group vs. 1/200 (0.5%) in the surgeons group (P = 0.69). No major complications occurred in either group. Mean hospital stay was 2 (range 0.5–26) and 2.3 (range 0.5–18) days in the trainees and surgeons groups, respectively (P = 0.25). There were 13/500 vs. 5/200 readmissions (P = 0.92), and 1/500 vs. 1/200 reoperations in the trainees and surgeons groups, respectively (P = 0.91). Conclusion Allowing senior pediatric surgery trainees to perform laparoscopic appendectomies without supervision to stimulate surgical autonomy is safe and does not compromise patient outcomes. Level of evidence III.

Background Recent studies suggest improved outcomes for children undergoing thyroidectomy at high-volume pediatric surgery centers. We present outcomes after thyroid surgery at a single center and advocate for referral to high-volume centers for multidisciplinary management of these children. Methods Medical records were reviewed for all pediatric patients undergoing thyroid surgery at a single institution from 2009 through 2017. Routine recurrent laryngeal nerve and parathyroid hormone monitoring was used. Lymph node dissections were performed in appropriately selected cancer patients. Data collection focused on pathologic diagnosis, surgical technique, and surgical complications, including postoperative hematoma, neurapraxia, permanent nerve damage, hypocalcemia, and transient and permanent hypoparathyroidism. Results From 2009 through 2017, 464 patients underwent thyroid surgery. Median age of the cohort was 15 years (range 2–24). Thirty-three percent were diagnosed with benign nodules (n = 151), 36% with papillary or follicular thyroid cancer (n = 168), 27% with Graves’ disease (n = 124), 3% with medullary thyroid cancer (n = 14), and 1.5% underwent prophylactic thyroidectomy for MEN2a (n = 7). Six patients required return to the OR for hematoma evacuation including 5 patients after surgery for Graves’ disease (RR 8.7, 95% CI 1.06–71.85). In sixteen cases, concern about neurapraxia resulted in laryngoscopy, revealing eleven patients with vocal cord paresis. Two of these patients demonstrated a persistent deficit at 6 months postoperatively (0.4%). Thirty-seven percent of patients had transient hypoparathyroidism (n = 137), and two patients had persistent hypoparathyroidism 6 months after total thyroidectomy (0.6%). There was no significant difference in either hypocalcemia or hypoparathyroidism after total thyroidectomy based on age or diagnosis. Conclusions Characterizing outcomes for pediatric patients based on diagnosis will assist in preoperative counseling for patients and their families. This high-volume center reports low complication rates after pediatric thyroid surgery, highlighting that referral to high-volume centers should be considered for children and adolescents with thyroid disease requiring surgery. Level of evidence Level IV

Introduction: We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of supporting premature fetal lambs and have been able to replicate hypoxic in utero conditions by controlling fetal oxygen delivery. In this study, we investigated the fetal mitochondrial response to hypoxia. Methods: Eight premature fetal lambs were delivered via hysterotomy and transitioned to extra-uterine support for 3 weeks. The lambs were divided into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and hypoxic fetuses in which oxygen delivery was significantly reduced. Control fetuses were delivered via hysterotomy but not cannulated. Measurements of mitochondrial membrane potential (MMP) were performed in peripheral blood mononuclear cells. Results: There were no significant differences in MMP between normoxic EXTEND fetuses and controls. Hypoxic fetuses had significantly more depolarized mitochondria compared to normoxic fetuses overall, and these changes were specifically appreciated in weeks 1 and 2, but not by week 3. Hypoxic fetuses had significantly elevated levels of HIF-1α compared to normoxic fetuses in the first 2 weeks. Discussion: Normoxic fetal lambs supported by EXTEND demonstrate normal mitochondrial function as evidenced by equivalent membrane potentials compared to control fetuses. Hypoxic fetuses exhibit mitochondrial dysfunction, though they do show evidence of adaptation after 3 weeks of hypoxic exposure.

Mae Euroepinomics-Res Mae; International audience; Objective We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype–phenotype correlations.Methods We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed.Results We describe 17 unrelated affected individuals carrying 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent associated neurological features. With the exception of one patient who experienced a single seizure, all patients had epilepsy, characterised by falls or head drops due to atonic or myoclonic seizures, (myoclonic) absences and/or eyelid myoclonia. Triggers of seizures were frequent (n=7). Seizures were pharmacoresistant in half of the patients. The severity of the epilepsy did not correlate with the presence of autistic features or with the severity of cognitive impairment. Mutations were distributed throughout the gene, but spared spliced 3′ and 5′ exons. Seizures in patients with mutations in exons 4–5 were more pharmacoresponsive than in patients with mutations in exons 8–15.Conclusions SYNGAP1 encephalopathy is characterised by early neurodevelopmental delay typically preceding the onset of a relatively recognisable epilepsy comprising generalised seizures (absences, myoclonic jerks) and frequent triggers.

High throughput genetic technologies offer the opportunity to gain precision in the diagnosis of numerous diseases and to better understand their molecular basis. However they bring new practical and ethical challenges, some of which are foreseeable and therefore amenable to the timely adoption of strategies to ensure that they are introduced and used in a just and beneficial manner. One way of foreseeing these challenges is to examine technologies that have already been transferred from research to the clinical setting in order to identify the ethical issues and develop strategies to move forward in an ethical way. One such model for new genetic technologies is Array Comparative Genomic Hybridization (aCGH), which has been gradually adopted in recent years as a standard technique in clinical genetics. CGH challenging current clinical practice regarding the detection and diagnosis of human chromosome abnormalities in intellectual disability (ID) and congenital malformations in children. Experience with aCGH has shown that it delivers an unprecedented volume of information for patients, counsellors, and health care providers but it also raises specific ethical challenges which can serve as signposts for potential issues with future, even more detailed, genetic technologies. These issues are described and illustrated through case histories, and their consequences for the patient-clinician relationship in genetic consultation are discussed. The consequences of employing this technology, as compared to the more traditional genetic diagnostic methods used in cases of intellectual disability are categorised into issues linked to 1) the vulnerable nature of patients who are mostly children, mentally retarded people or “future parents”; 2) the way in which information is controlled at each stage of the process, as a function of its potential relevance to the clinical condition being diagnosed, 3) the information related to conditions other than ID or “incidental findings” that become the rule with high throughput technologies. The issues highlighted by the clinical scenarios discussed here can be expected to occur with even greater frequency in the future as whole exome and whole genome sequencing are introduced. Building on our experience with the transfer and adoption of aCGH into clinical genetics, we have developed a grid of points to be considered when translating such technologies from research to clinic.