Combined Malformations Research Articles

Combined malformation of the genitals — penoscortical transposition and proximal hypospadias: a clinical case and literature review

A case of a rare combined defect - penoscortical transposition and scrotal hypospadias is presented. A two-stage correction of hypospadias was performed, and the second stage was combined with penile transposition, resulting in good functional and cosmetic results.

Adolescent female reproductive system dysplasia: a clinical study of 356 cases

Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

Atriovenous Malformation of Pinna (A Rare Case) At a Tertiary Care Hospital, Patna, Bihar

Introduction: Arteriovenous malformations are vascular abnormalities in which the arterial vasculature connects to the venous, leading to potentially disfiguring and life-threatening complications. Venous malformations (70 %) are the most common CVM (congenital vascular malformation), followed by lymphatic malformations (12 %),arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).The majority of these lesions are sporadic in nature.Case Report: A 15-year-old male came to E.N.T.OPD at PMCH with a history of swelling and skin discoloration of the right pinna (medial as well as lateral side) since last 2 years.Physical examination Vital signs were normal. Nopallor, no localized lymphadenopathy. A pulsatile swelling with areas of skin discoloration at the right pinna with no necrosis .Ear canal and the tympanic membrane- normal.On palpation Well defined welling, circumscribed margins, soft, non-compressible, spongy, non-tender, and pulsatile with a thrill. Bruit on auscultation.Investigations Routine tests were within normal limits. PTA- bilateral mild S.N.H.L.MRI-High flow vascular malformation seen in right retro auricular region with feeding vessels arising from right superficial temporal artery and branches of right maxillary artery.Treatment- Patient underwent sclerotherapy of the lesion. Postoperatively, the patient was evaluated in the E.N.T OPD at one, two and four weeks following sclerotherapy without recurrence of a mass, pulsation or bruit.

Association of spinal cord abnormalities with vertebral anomalies: an embryological perspective.

To analyze the relationship between spinal cord and vertebral abnormalities from the point of view of embryology. We analyzed the clinical and radiological data of 260 children with different types of spinal cord malformations in combination with vertebral abnormalities. Among 260 individuals, approximately 109 presented with open neural tube defects (ONTDs), 83 with split cord malformations (SCMs), and 83 with different types of spinal lipomas. Pathological spina bifida emerged as the most frequent vertebral anomaly, affecting 232 patients, with a higher prevalence in ONTD. Vertebral segmentation disorders, including unsegmented bars, butterfly vertebrae, and hemivertebrae, were present in 124 cases, with a higher prevalence in SCM. The third most common spinal anomaly group consisted of various forms of sacral agenesis (58 cases), notably associated with blunt conus medullaris, spinal lipomas, and sacral myelomeningocele. Segmental aplasia of the spinal cord had a typical association with segmental spinal absence (N = 17). The association between SCM and neuroenteric cyst/canal and vertebral segmentation disorders is strong. High ONTDs often coincide with pathological spina bifida posterior. Type 1 spinal lipomas and focal spinal nondisjunction also correlate with pathologic spina bifida. Segmental spinal absence or dysgenesis involves localized spinal and spinal cord aplasia, sometimes with secondary filar lipoma.

Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors

ObjectiveTo review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC.MethodsPatients diagnosed with JIA who received...

Associated congenital anomalies and genetic anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery

Objective This study’s aim was to determine the prevalence of chromosomal anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery (ARSA) and to evaluate its association with other congenital anomalies. Methods From September 2018 to October 2021, 668 ARSA cases were diagnosed by prenatal ultrasound in our hospital; cases with missed visits and a lack of chromosomal findings were excluded and 363 cases were eligible for enrollment. General information, ultrasound presentation, chromosomal findings and pregnancy outcomes were retrospectively analyzed. Results Among the 363 cases, 296 were isolated, and 67 were associated with structural abnormalities or soft marker abnormalities. The proportion of fetuses with chromosomal abnormalities in the isolated ARSA group was significantly lower than that in the non-isolated ARSA group (p < .001). In the non-isolated ARSA group, 22 cases were combined with other soft marker abnormalities and 45 cases were combined with structural abnormalities. The most frequent structural abnormality coexisting with ARSA was cardiac malformations (38.81%). Conclusion The most common combined malformation in ARSA is intracardiac malformation. Isolated ARSA has a low risk of chromosomal abnormalities, so invasive chromosomal testing is not recommended. Non-isolated ARSA has a high incidence of chromosomal abnormalities, so early karyotyping should be recommended.

Features of the Genitourinary System in Anorectal Malformations in Children

In anorectal anomalies, combined malformations of the urogenital system are often observed [1,5,7]. This can be explained by the close relationship between the embryonic development of these organs and systems. It is no coincidence that a lot of attention in the literature of the last decade is paid to urological problems of anorectal anomalies [ 12,15,20]. However, the true frequency has not yet been established and the structure of pathological conditions of urogenital system in anorectal anomalies has not been fully studied, the consequences of their delayed diagnosis have not been analyzed, treatment and tactical and operative technical aspects have not been developed and the organizational side of the issue needs improvement

Validation and effect of the NASA-TLX score on the assessment of the workload of pediatric robotic operations.

The objective of the study was to assess the validity of the NASA-TLX score in rating the workload of pediatric robotic operations. The workload of 230 pediatric gastrointestinal and thoracic robotic operations was rated using the NASA-TLX score. The difference between the high workload group and the low workload group in each subscale of the NASA-TLX score was analyzed. The correlation of each subscale with the total workload score in the high workload group and low workload group was also analyzed. A logistic regression analysis was subsequently conducted to assess the effects of different factors (sex, age, weight, procedure duration, procedure specialties, combined malformation and blood loss) on the workload. The average NASA-TLX score was 56.5 ± 5.1 for the total group, 56.9 ± 5.0 for the gastrointestinal group and 54.6 ± 4.8 for the thoracic group, p = 0.007. The score of the high workload group was 62.7 ± 3.2, while it was 50.6 ± 2.7 for the low workload group (p < 0.001). The score on each subscale was also significantly different between the high and low workload groups. In the high workload group, a stronger correlation was observed between the total score and TD and Fr and a lower correlation with MD and Pe. In the low workload group, all six subscales showed a moderate correlation with the total score. A multivariate logistic regression analysis revealed that the procedure duration was an independent influencing factor for a higher workload score. NASA-TLX is a valid tool to rate the surgeon's workload in pediatric robotic surgery. A longer operative time contributes to a higher workload.

Sirolimus Early Treatment in Vascular Anomalies Leads to a Better Response

Objectives: Sirolimus has become a relevant drug in the treatment of vascular anomalies, initially relegated to rescue therapy for refractory lesions but more recently has become first line. Our objective is to determine when it is best to start sirolimus treatment. Methods: A retrospective review of patients with vascular anomalies treated with sirolimus during a 9-year period was performed. The variables analyzed included subtype of vascular anomaly, age at the start of treatment, sirolimus dosage and levels, response, and duration of treatment among others. Results: One hundred twenty-two patients were included and classified according to ISSVA in: tumor (7), lymphatic malformation (60), venous malformation (16), combined malformations (18), associated overgrowth (8), and others (15). Overall response was positive in 90.8%. Median duration of treatment was 32 months (0–116). Response was not influenced by dosage or levels, neither by the subtype of vascular anomaly, location, extension, symptoms, genetic testing nor previous treatments. However, the lower the age of starting sirolimus, the better the response, mainly under 5 years of age (P = 0.004). At 6 months, 67% of patients had responded while at 12 months &gt;84% did. By age, patients &lt;5 years showed positive response at a median time of 2 months, compared to &gt;5 months from older patients. Time until a positive response was not influenced by subtype or severity. Conclusion: Overall response to sirolimus was good and most patients responded irrespective of their severity in location, extension or symptoms. Patients &lt;5 years old respond better and faster making our goal to attempt for an early treatment.

Anatomical features of the malformation, methods and results of bladder exstrophy primary closure. Literature review

Background. Bladder exstrophy (ВE) is a complex combined malformation of the organs of the genitourinary system, the methods of treatment of which have not been fully developed. Materials and methods. When writing a literature review, materials devoted to the problem of BE published in the databases of PubMed, eLIBRARY (the scientific electronic library of Russia), Scopus, Medline, EMBASE, websites and journals of foreign and domestic professional associations were used. Results. Multiple anatomical features of the structure of organs and entire systems make BE one of the most difficult-to-correct congenital malformations in the field of pediatric urology, requiring a comprehensive, systematic approach to diagnosis and treatment. The paper reflects the key, in our opinion, positions of the author’s Kelly, Mainz operations, the approaches of Schrott–Erlangen, CPRE, MSRE, as well as the view of a number of authors on osteotomy. Conclusion. The abundance of primary closure techniques and the difference in views of numerous authors on the required amount ofsurgical intervention presented in thisliterature review are indisputable proof ofthe relevance ofthe problem.

The results of the esophageal atresia treatment in Far Eastern Federal District, Russian Federation

Objective: The purpose of this study was to analyze the structure of morbidity and the results of treatment of children with EA in the Far Eastern Federal District.Methods: The retrospective analysis of the annual reports of pediatric surgeons of all 11 regions of the Far Eastern Federal District. Total 46 children with EA were born from 2019 to 2021, 1 child died because of severe comorbidity before surgery, 1 was operated in Moscow. 44 children having A, B, C, D types of EA by Gross were treated by regional surgeons.Results: 64% of children were boys and 36% - girls, half of the children were born prematurely, every fourth was fed before getting diagnosis. The most common form was EA with lower tracheoesophageal fistula (93%). Combined malformations were found in 60% of cases, the most frequent was cardiac anomaly. Anastomosis was applied in 86% of operated, the rest underwent staged procedures. 81% are alive after applying anastomosis, 33% after coloesophageal replacement. Thoracoscopic AP treatment is widely used in regions having much higher population density than the Far East, but there is a tendency to improve this indicator. As for our district, there are several ways to improve surgical care: concentration of patients of the same profile in one or two regional centers or involvement of leading Russian specialists in providing high-tech medical care.Conclusions: The peculiarities of the logistics of the region lead to the idea of creating a single Far Eastern multidisciplinary surgical center providing counseling, transportation, diagnostics and treatment of patients with congenital malformations at the modern level.

The Sonographic Features of Malformation in Fetal Echogenic Bowel and Its Relationship With Chromosome Abnormalities.

The aims of this study were to analyze the sonographic features and clinical prognosis of fetal echogenic bowel (FEB) and to evaluate the value of FEB in the prediction of fetal chromosomal abnormalities. Eight hundred eighty-two fetuses with FEB were selected. The ultrasonographic features and the chromosomal examination were retrospectively analyzed. Among the 882 FEB, 272 (30.8%) cases had malformation. The most common malformation was cardiovascular malformation (21.6%), followed by urinary malformation (9.0%), craniocerebral malformation (6.8%), and gastrointestinal malformations (5.6%). According to other combined ultrasound abnormalities, the FEBs were divided into 4 groups: isolated FEB group (490 cases), ultrasound soft indicators group (130 cases), single malformation group (117 cases), and multiple malformation group (145 cases). A total of 45 cases (5.1%) were detected with chromosomal abnormalities. Compared with isolated FEB group, the rate of chromosomal abnormality in other 3 groups was significantly higher. Among 490 cases of isolated FEB, 114 cases of isolated FEB group with adverse pregnancy outcomes were selected as the experimental group, and 376 cases of FEB group with good prognosis were selected as the control group. There were significant differences of the location, shape, intensity, and progression between the 2 groups. Multivariate logistic regression analysis showed that central location and progression of FEB were independent risk predictors of poor prognosis. The combined malformation rate is high for FEB fetuses. The fetal systems should be carefully examined when FEB is found in prenatal ultrasound.

Nonsurgical correction of cryptotia in children older than early neonates

Objective:To study the clinical application of nonsurgical correction of cryptotia in children older than 6 months. Methods:The children with cryptotia deformity treated in Guangzhou Women and Children's Medical Center from January 2017 to January 2021 were divided into two groups according to their ages. The study group was over 6 months old and the control group was under 6 months old. They were treated with a Earwell auricle correction system, the follow-up was continued for 3-6 months, and the correction effects, complications and recurrence after the treatment were calculated in the two groups. Results:The average time of the treatment start stage and consolidation stage in the study group was（20.29±7.14） days and（31.82±9.65） days, and respectively the control group was（7.5±3.21） days and（16.64±6.53） days, the difference in treatment time between the two groups was statistically significant（P=0.001）. The effective rate in the study group was 90.91%（20/22）, and the effective rate in the control group was 96.43%（27/28）, there was no statistically significant difference between the two groups（P=0.576）. The recovery rate in the study group was 31.82%（7/22）, and the recovery rate in the control group was 85.71%（24/28）, the cure rate of the control group was higher than that of the study group（P=0.002）. Complications occurred in both groups. The most common complications in the study group were skin redness and swelling 18 cases（81.82%） and stent shedding 16 cases（72.73%）, pressure ulcers followed by 12 cases（54.55%）. The most common complication in the control group was skin eczema 9 cases（32.14%）, pressure ulcers 6 cases（21.43%）, stent shedding 5 cases（17.86%）. There was a statistical difference in the incidence of complications between the two groups（P<0.05）. Conclusion:For older children with cryptotia, Earwell correction systems can still be actively tried to correct hidden ears, but only the hidden auricle can be pulled out. Other combined malformations such as helix adhesion, dysplasia of the upper helix, etc. cannot be improved. Before treatment, it is necessary to fully communicate with the parents about possible complications during the treatment process. Encouraging children and parents to insist on wearing the correction system is the key to successful treatment.

Combined malformation of the biliary tract

Anomalies in the biliary tract development are a relatively rare pathology in the practice of a pediatric surgeon. A combination of two or more defects of the biliary tract is even less common. The article presents literature data and own clinical observation of a child with a combination of a cyst of the common bile, or hepatic, duct (common bile duct) and an additional bile duct. The anatomical structure of the biliary tract was identified before surgery using magnetic resonance cholangiography. Based on the analysis of literature data and our own observation, we propose an algorithm for diagnostic measures in children with malformations of the biliary tract, which helps to avoid intraoperative injuries.

Congenital hypopituitarism with monosomy of chromosome 18

Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.Сhromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them.

Sirolimus (Rapamycin) for Slow-Flow Malformations in Children

Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers. Statistical analysis was performed on an intent-to-treat basis from December 4, 2019, to November 10, 2020. Patients underwent an observational period, then switched to an interventional period when they received oral sirolimus (target serum levels, 4-12 ng/mL). The switch time was randomized from month 4 to month 8, and the whole study period lasted 12 months for each patient. The primary outcome was change in the volume of vascular malformations detected on magnetic resonance imaging scan (with centralized interpretation) per unit of time (ie, between the interventional period and the observational period). Secondary outcomes included subjective end points: pain, bleeding, oozing, quality of life, and safety. Among the participants (35 girls [59.3%]; mean [SD] age, 11.6 [3.8] years), 22 (37.3%) had a pure venous malformation, 18 (30.5%) had a cystic lymphatic malformation, and 19 (32.2%) had a combined malformation, including syndromic forms. Variations in the volume of vascular malformations detected on magnetic resonance imaging scans associated with the duration period were not overall significantly different between the interventional period and the observational period (all vascular malformations: mean [SD] difference, -0.001 [0.007]; venous malformations: mean [SD] difference, 0.001 [0.004]; combined malformations: mean [SD] difference, 0.001 [0.009]). However, a significant decrease in volume was observed for children with pure lymphatic malformations (mean [SD] difference, -0.005 [0.005]). Overall, sirolimus had positive effects on pain, especially for combined malformations, and on bleeding, oozing, self-assessed efficacy, and quality of life. During sirolimus treatment, 56 patients experienced 231 adverse events (5 serious adverse events, none life-threatening). The most frequent adverse event was an oral ulcer (29 patients [49.2%]). This observational-phase randomized clinical trial allows for clarifying the goals of patients and families when starting sirolimus therapy for children older than 6 years. Pure lymphatic malformations seem to be the best indication for sirolimus therapy because evidence of decreasing lymphatic malformation volume per unit of time, oozing, and bleeding and increasing quality of life was found. In combined malformations, sirolimus significantly reduced pain, oozing, and bleeding. Benefits seemed lower for pure venous malformations than for the 2 other subgroups, also based on symptoms. ClinicalTrials.gov Identifier: NCT02509468; clinicaltrialsregister.eu Identifier: 2015-001096-43.

Повреждения головки полового члена при обрезании крайней плоти: причины, способы лечения и меры профилактики

INTRODUCTION Penile glans amputation during circumcision is a rare but potentially devastating complication. The mechanism and causes are poorly understood and incomprehensible. It is important to identify the causes of these complications, to suggest a mechanism and to propose prevention measures. MATERIALS Between 2005 and 2019, six patients with penile glans amputationafter circumcision were analyzed. All were operated without medical evidence, for religious reasons. THE RESULTS The operations were performed by local anesthesia, at home - in 5 patients, in 1 child - at polyclinic. All children were circumcised by scalpel with guillotine method, without visualization of glans. Partial amputation of penile glans was observed in 2 children (33.3%). Complete cut-off of the glans at the level of the coronal sulcus was revealed in 4 boys (66.6%). Meatoplasty with urethral mobilizations was performed 2 patients (33.3%) with partial amputation. The tops of corpus cavernous was covered of with the remnants of the skin of penile shaft in two boys (33.3%). Glansplasty was performed in 2 other patients (33/3%), using a labial mucosa graft to reconstruct the shape of glans and glanular groove. The follow up have showed meatostenosis in two boys (33.3%) in the first 2 months after surgery. One child required repeated meatoplasty (16.6%), another had a recovery of normal urine flow rates after urethral dilatation and stenting (4 weeks). CONCLUSION Visual control of the glans position during circumcision will prevent the amputation. Guillotine techniques including, Mogen clamp-type devices, are considered potentially dangerous. Circumcision in newborns, without general anesthesia, in the presence of swelling of the foreskin have an increased risk of glans damage. Preliminary examination of the glans and adequate release of preputial adhesions help to prevent complication of circumcision and to identify combined malformations (hypospadia, epispadia, concealed penis.).

Expression of β1 adrenergic receptor in vascular anomalies in children.

ObjectiveControversial, heterogeneous, and inconsistent responses to beta-blockers have been reported in some cases of infantile proliferative hemangiomas. On the basis of these clinical observations, we aimed to examine the β1 adrenergic receptor (β1-AR) protein expression distribution among different types of pediatric vascular anomalies.MethodsImmunohistochemistry (IHC) was performed for β1-AR on 43 surgical specimens.ResultsWe found positive β1-AR IHC staining in all intramuscular hemangiomas, capillary–lymphatic, lymphatic, venous, and combined malformations, and Masson’s tumor cases, as well as in 7 of 10 cases of proliferative infantile hemangiomas.ConclusionsOur research demonstrates, for the first time, the degree of heterogeneous expression of β1-AR among pediatric vascular malformations. Our results support the need for β1-AR assessment in pediatric vascular anomalies to select cases with a robust response to β1-selective blockers. β1-AR assessment may have a strong impact on therapeutic refinement for pediatric vascular anomalies by selecting cases with a stronger response to beta-blockers.

Obstructive Sleep Disorders in Down Syndrome's Children with and without Lower Airway Anomalies.

(1) Background: Obstructive sleep apnea (OSA) and lower airway anomalies are both highly prevalent in children with Down syndrome (DS). However, little is known on the interaction between both. We aim to investigate the co-occurrence of OSA (defined as obstructive apnea/hypopnea index (oAHI) ≥ 2/h) and lower airway anomalies in children with DS and explore their impact on OSA severity and treatment outcome. (2) Methods: Retrospective analysis of data from airway endoscopy and polysomnography (PSG) in a cohort of children with DS. (3) Results: Data on both lower airway evaluation and PSG were available for 70 patients with DS. Our study population was relatively young (mean age 3.5 years), not obese and presented with severe OSA (mean oAHI 13.1/h). Airway anomalies were found in 49/70 children (70%), most frequently laryngomalacia, tracheomalacia or a combined airway malformation. In the remaining 21 cases (30%), endoscopy was normal. A comparison between both groups showed a similar distribution of gender, age and BMI z-scores. The prevalence of OSA was not significantly higher in DS patients with airway anomalies (89.6% vs 71.4%, p = 0.078). Additionally, OSA severity or treatment choice (conservative, upper airway surgery or CPAP) were not significantly different. Follow-up data (available for 49/70 patients) showed a significant improvement of OSA in both groups. There is a not significant tendency to more patients with persistent OSA among those with lower airway anomalies (34.3% vs 7.1%, p = 0.075). (4) Conclusions: We found no significant differences in OSA severity, treatment choice or outcome between children with DS with and without lower airway anomalies. Further studies should investigate the role of DISE-directed treatment and compare the outcome of different treatment modalities in larger patient groups.

P–546 Exome sequencing and preimplantation genetic testing for unexplained recurrent fetal malformations

Abstract Study question Could patient suffering unexplained recurrent fetal malformations be benefit of PGT-M by exome sequencing mutations identification? Summary answer Patients suffering unexplained recurrent fetal malformations could be benefit of the use of exome sequencing in combination to PGT-M to have a healthy live birth. What is known already Fetal malformations account for approximately 3% of live births and causes include: chromosomal abnormalities, exposure to toxic substances or teratogens and infections. Recently, studies have shown that several monogenic diseases are linked to fetal abnormalities. However, because of the large number of potential genes, genetic testing is challenging. Exome sequencing is widely used to detect genetic mutations and has emerged as a useful tool for finding the genetic cause of fetal abnormalities. The aim of this study was to show how exome sequencing in patients suffering unexplained recurrent fetal malformations in combination to PGT-M could lead to successful healthy newborn. Study design, size, duration Case report of a non-consanguineous couple with unexplained, recurrent fetal malformations. Couple were recruited during clinical consultation for unexplained recurrent fetal malformations at a private reproductive medicine clinic. The couple had two malformed fetus with the same congenital abnormalities: hydrocephalus, cerebellar vermis agenesis, cerebellar hypoplasia and enlarged cisterna magna. Patients signed written informed consent regarding to exome testing. For fetal sample, informed consent was obtained from parents. Participants/materials, setting, methods Sample of the affected fetus were provided. Parental genomic DNA was extracted from peripheral blood. Exome sequencing was performed using TrusightOne (Illumina®). FASTAQ data were processed through BWA and GATK algorithm. VCF files were analysed using Variant Interpreter software. After genetic counselling, PGT-M was performed using linkage polymorphic markers analysis and mutation sequencing. Embryo biopsy was carried at blastocyst stage. Embryos were vitrified and one healthy embryo was thaw and transfer in a subsequent cycle. Main results and the role of chance An homozygous novel pathogenic mutation c.641 C&amp;gt;T (p.Ala214Val) in FVLCR2 gene was found. The parents were heterozygous carriers revealing that the detected variant follow an autosomal recessive pattern. The FLVCR2 (14q24.3) gene encodes a transmembrane protein that belongs to the major facilitator superfamily of secondary carriers that transport small solutes in response to chemiosmosis ion gradients, such as calcium. Mutations in this gene are related to fetal central nervous system defects. This disorder is diagnosed prenatally and is lethal. PGT-M was recommended during genetic counselling. After control ovarian stimulation 14 oocytes were retrieved and finally 4 embryos were suitable for embryo biopsy at blastocyst stage. One embryo was diagnosed as healthy, two affected and one heterozygous carrier. The healthy embryo was thaw and transferred and a healthy male baby was born. Limitations, reasons for caution Exome sequencing has technical limitations: only covers mutations in coding regions and does not cover noncoding regions of the genome. It also cannot reliably detect copy-number variants at single gene level. Wider implications of the findings: This study offers strong evidence of exome-sequencing as a new diagnostic strategy and powerful tool discovering the underlying etiology of recurrent fetal malformations and identifying new genes important for human development. Using this strategy in combination with PGT-M, clinicians can help couples with recurrent fetal malformations to have healthy newborns. Trial registration number Not applicable