Aplasia Cutis Congenita of the Scalp with Bone Defect and Exposed Sagittal Sinus in Trisomy 13 Newborn - a Case Report.

Background: Aplasia cutis congenita is a heterogeneous disorders group with a rare reported incident of 0.5 to 1 in 10,000 births. ACC can be associated with physical defects or syndrome that may help in diagnosis, prognosis and further evaluation of the patient. Trisomy 13 is one of the most common fetal life limiting diagnosis which is associated with ACC of membranous type scalp. Objective: In this article, we report cases of aplasia cutis congenita of the scalp with dura and bone defect and exposed sagittal sinus in newborn diagnosed to have trisomy 13. It emphasizes the importance of ACC associated syndrome which is having high mortality prior to surgical intervention. Case presentation: The patient was born at 35 weeks of gestation. Her physical examination revealed a newborn girl with dysmorphic facial features including widely separated eyes, downward slanting of the palpebral fissure, microphthalmia, retrognathia, and low seat ears. She had area of loss of scalp skin and skull bone with seen brain tissue and sagittal sinus were exposed that was measure 6 by 5 cm in size. Additionally, she had a clenched fist and overlapping fingers and rocker bottom feet. Laboratory investigations include basic labs and the TORCH screen was negative. On the 9th day of life, a chromosomal analysis showed a female karyotype with three copies of chromosome number 13 in all 20 metaphase cells counts. Conclusion: The patient was managed conservatively. However, a multidisciplinary team agreed on do not resuscitate with no further surgical intervention as survival rate of trisomy 13 is poor.

The common trisomy syndromes, their cardiac implications, and ethical considerations in care.

PURPOSE OF REVIEW: To review the incidence of congenital heart disease in the trisomies, highlight the history of cardiac surgery in trisomy 21 comparing it to the increase in cardiac surgery in trisomies 13 and 18, discuss ethical issues specific to trisomies 13 and 18, and suggest a pathway of shared decision-making in the management of congenital heart disease in trisomy 13 and 18, specifically congenital heart surgery. RECENT FINDINGS: Congenital heart disease is prevalent in the trisomies and the management of these defects, especially surgical intervention, has changed. In the late 20th century, survival after cardiac surgery in trisomy 21 vastly improved, significantly decreasing morbidity and mortality secondary to pulmonary hypertension. Similarly, procedures and surgeries have been performed with increasing frequency in trisomy 13 and 18 patients and concomitantly, survival in this patient population is increasing. Yet across the United States, the willingness to perform cardiac surgery in trisomy 13 and 18 is variable, and there is ethical controversy about the correct action to take. To address this concern, a shared decision-making approach with an informed parent(s) is advised. SUMMARY: As the care and management of congenital heart disease changed in trisomy 21, so too it has with trisomy 13 and 18. Physicians and parents should develop goal-directed treatment plans balancing the risk versus benefit and consider cardiac surgical repair if feasible and beneficial.

Otolaryngologic Manifestations of Trisomy 13 and Trisomy 18 in Pediatric Patients.

OBJECTIVE: The survival rate of patients with trisomy 13 and trisomy 18 has increased dramatically over the past two decades. We sought to comprehensively describe the otolaryngologic clinical characteristics and procedures required for these patients at our institution. METHODS: We performed algorithmic identification of patients with a diagnosis of trisomy 13 and trisomy 18 for whom the otolaryngology service provided inpatient or outpatient care at our institution between the dates of February 1997 and March 2021. RESULTS: Of the 47 patients studied, 18 patients had a diagnosis of trisomy 13, and 29 had a diagnosis of trisomy 18. Complete trisomy was present in 44% (8/18) of trisomy 13 patients and 55% (16/29) of trisomy 18 patients. 81% of patients were living at the time of the study. About 94% (44/47) of patients required consultation with another specialty in addition to Otolaryngology. Overall, the most common diagnoses among this cohort were gastroesophageal reflux disease (47%), dysphagia (40%), otitis media (38%), and obstructive sleep apnea (34%). Nearly three-quarters (74%) of patients studied required an otolaryngologic procedure. The most common surgical procedure was tonsillectomy and/or adenoidectomy. Patients with trisomy 18 were significantly more likely to have external auditory canal stenosis and obstructive sleep apnea whereas patients with trisomy 13 were more likely to have cleft lip and palate. CONCLUSIONS: Patients with a diagnosis of trisomy 13 or 18 often require multidisciplinary management and the range of required care spans the breadth of otolaryngology. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1501-1506, 2023.

Surgical History and Outcomes in Trisomy 13 and 18: A Thirty-year Review.

BACKGROUND: Patients with Trisomy 13(T13) and 18(T18) have many comorbidities that may require surgical intervention. However, surgical care and outcomes are not well described, making patient selection and family counseling difficult. Here the surgical history and outcomes of T13/ T18 patients are explored. METHODS: A retrospective review of patients with T13 or T18 born between 1990 and 2020 and cared for at a tertiary children's hospital (Riley Hospital for Children, Indianapolis IN) was conducted, excluding those with insufficient records. Primary outcomes of interest were rates of mortality overall and after surgery. Factors that could predict mortality outcomes were also assessed. RESULTS: One-hundred-seventeen patients were included, with 65% T18 and 35% T13. More than half of patients(65%) had four or more comorbidities. Most deaths occurred by three months at median 42.0 days. Variants of classic trisomies (mosaicism, translocation, partial duplication; p = 0.001), higher birth weight(p = 0.002), and higher gestational age(p = 0.01) were associated with lower overall mortality, while cardiac(p = 0.002) disease was associated with higher mortality. Over half(n = 64) underwent surgery at median age 65 days at time of first procedure. The most common surgical procedures were general surgical. Median survival times were longer in surgical rather than nonsurgical patients(p<0.001). Variant trisomy genetics(p = 0.002) was associated with lower mortality after surgery, while general surgical comorbidities(p = 0.02), particularly tracheoesophageal fistula/esophageal atresia(p = 0.02), were associated with increased mortality after surgery. CONCLUSIONS: Trisomy 13 and 18 patients have vast surgical needs. Variant trisomy was associated with lower mortality after surgery while general surgical comorbidities were associated with increased mortality after surgery. Those who survived to undergo surgery survived longer overall. LEVEL OF EVIDENCE: III.

Morbidity and mortality following noncardiac surgical procedures among children with autosomal trisomy.

BACKGROUND: Trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21) are the most common autosomal trisomies. One unifying feature of all trisomies is their association with major congenital malformations, which often require life-prolonging surgical procedures. Few studies, mostly among cardiac surgery patients, have examined the outcome of those who undergo surgical procedures. We examined the differences in postsurgical outcomes between the trisomy groups. METHOD: Using the National Surgical Quality Improvement Program dataset, we identified children (<18 years of age) with T13, T18, or T21 who underwent noncardiac surgery (2012-2018). We estimated the incidence of mortality and indicator of resource utilization (unplanned reoperation, unplanned tracheal reintubation, and extended length of hospital stay). RESULTS: Of the 349 158 inpatient surgical cases during the study period, we identified 4202 children with one of the autosomal trisomies of interest (T13: 152; T18: 335; and T21: 3715). The rates of postoperative mortality were substantially higher for T18 and T13 than T21 and nontrisomy children (T18 vs. T21: 11.1% vs. 1.6%, adjusted odds ratio: 5.01, 95%CI: 2.89,8.70, p < .01), (T13 vs. T21: 8.1% vs. 1.6%, adjusted odds ratio: 2.86, 95%CI: 1.25,6.54, p = .01). Children with T18 had the highest rates of extended length of stay (62.7%) and prolonged mechanical ventilation (32.5%). T18 and T13 neonates had the highest surgical mortality burden (T13: 26.5%, T18: 31.8%, and T21: 2.8%). CONCLUSION: Approximately, one-third of T18 and T13 neonates, who had surgery, died, underscoring the lethality of these trisomies and the need for a comprehensive preoperative ethical discussion with families of these children.

Sleep disordered breathing in children with trisomy 13 and trisomy 18.

PURPOSE: While the prevalence of obstructive sleep apnea (OSA) is well documented in trisomy 21, there has been little published about the incidence in trisomy 13 (T13) and trisomy 18 (T18). Trisomies 13, 18, and 21 have overlapping clinical features that make patients prone to OSA. Because the literature regarding OSA in T13 and T18 children is limited, we performed a retrospective chart review to investigate the characteristics of these patients. METHODS: We reviewed the medical records of children with T13 or T18 seen at seen at a single urban tertiary children's hospital for sleep disordered breathing from 1/1/10 to 5/1/18. Candidates were selected based on ICD-9 diagnosis and procedural codes. RESULTS: We identified 21 T18 patients that had documented symptoms of SDB, of which 3 were diagnosed with OSA, 11 had clinical SDB, and 7 had snoring. Of the T13 patients, 10 had documented symptoms of SDB, of which 1 patient was diagnosed with OSA, 7 with clinical SDB, and 2 with snoring. In both T13 and T18 patients, anatomical features included micrognathia/mandibular hypoplasia, small mouth/small airway, midface hypoplasia, abnormal/difficult airway, glossoptosis, hypotonia, and GERD. Endoscopic findings included laryngomalacia and/or tracheomalacia, adenoid and lingual tonsil hypertrophy, and inferior turbinate hypertrophy. Surgical interventions performed in T13 and T18 patients included adenoidectomy, lingual tonsillectomy, and tracheostomy. Of the 32 T13 and T18 patients, 15 had to be intubated for respiratory insufficiency. CONCLUSION: The results of our study suggest that T13 and T18 patients are at increased risk for OSA due to common features found in this population. These findings indicate a need for otolaryngologist intervention to increase both survival and quality of life in this population.

Sinus of Valsalva Aneurysm in a Patient With Mosaic Trisomy 13: Case Report and Brief Review of the Literature.

This report describes a unique case involving an obese 16-year-old boy with a mosaic form of trisomy 13 and no previous cardiac history who presented with a new murmur, hypertension, pleural effusions, and congestive heart failure in the context of sore throat and fever. Evaluation revealed a diagnosis of ruptured noncoronary sinus of Valsalva (SOV) aneurysm. The diagnosis and surgical management of a ruptured noncoronary SOV aneurysm in a pediatric patient are briefly outlined. An SOV aneurysm is an anatomic dilation of one of the sinuses of the aortic root. Aneurysmal dilation occurs more commonly in the right aortic sinus (70%-80%), compared to the noncoronary sinus (23%-25%), and more rarely the left coronary sinus (5%). Rupture of these aneurysms has been reported to be both spontaneous and secondary to physical exertion, hypertension, or trauma. Signs of rupture include a continuous murmur, patients may present with chest pain or with symptoms of acute congestive heart failure. Diagnosis, in this case, was made by transthoracic echocardiography with careful interpretation of color Doppler images.

Cardiac Surgery in Patients With Trisomy 13 and 18: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.

Background Congenital heart disease is common in patients with Trisomy 13 (T13) and Trisomy 18 (T18), but offering cardiac surgery to these patients has been controversial. We describe the landscape of surgical management across the United States, perioperative risk factors, and surgical outcomes in patients with T13 and T18. Methods and Results Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database with T13 and T18 who underwent cardiac surgery (2010-2017) were included. There were 343 operations (T13: n=73 and T18: n=270) performed on 304 patients. Among 125 hospitals, 87 (70%) performed at least 1 operation and 26 centers (30%) performed ≥5 T13/T18 operations. Operations spanned the full spectrum of complexity with 29% (98/343) being in the highest categories of estimated risk. The operative mortality rate was 15%, with a 56% complication rate. Preoperative mechanical ventilation was associated with an odds ratio of mortality >8 for both patients with T13 and T18 (both P<0.012) while presence of a gastrostomy tube (odds ratio, 0.3; P=0.03) or prior cardiac surgery (odds ratio, 0.2; P=0.02) was associated with better survival in patients with T18 but not patients with T13. Conclusions Data from this nationally representative sample indicate that most centers offer surgical intervention for both patients with T13 and T18, even in highly complex patients. However, the overall mortality rate was high in this select patient cohort. The association of preoperative mechanical ventilation with mortality suggests that this subset of patients with T13 and T18 should perhaps not be considered surgical candidates. This information is valuable to clinicians and families for counseling and deciding what interventions to offer.

Mortality and Resource Use Following Cardiac Interventions in Children with Trisomy 13 and Trisomy 18 and Congenital Heart Disease.

We sought to evaluate the mortality, risk factors for mortality, and resource utilization following cardiac interventions in trisomy 13 (T13) and 18 (T18) children. All T13 and T18 children who underwent a cardiac intervention from January 1999 to March 2015 were identified from the Pediatric Health Information System database. Data collected included demographics, type of congenital heart disease (CHD), cardiac interventions, comorbidities, length of stay (LOS), hospital charges, and deaths (within 30 days). Logistic regression analysis was used to determine factors associated with mortality. There were 49 (47% females) T13 and 140 (67% females) T18 subjects. The two cohorts were similar in distribution for race, geographic region, insurance type, and median household income. The most common CHD in both groups was a shunt lesion followed by conotruncal defects. Compared to T18, the T13 cohort had higher mortality (29% vs. 12%), tracheostomies (12% vs. 4%), gastrostomies (18% vs. 6%), and overall resource use (P < 0.05 for all). White race (OR 0.23, 95% CI 0.06-0.81) in T13 and older age (in weeks) at surgery in T18 (OR 0.75, 95% CI 0.64-0.86) were associated with lower mortality. A select group of T13 and T18 CHD patients can undergo successful cardiac interventions, albeit with a higher mortality and resource use. T13 patients have higher mortality and resource use compared to T18. In T13 and T18 patients, interventions for CHD may be an acceptable and ethical option following a careful individualized selection and counseling by a team of experts.

Congenital Heart Surgical Admissions in Patients with Trisomy 13 and 18: Frequency, Morbidity, and Mortality.

Congenital heart defects are common among patients with trisomy 13 and 18; surgical repair has been controversial and rarely studied. We aimed to assess the frequency of cardiac surgery among admissions with trisomy 13 and 18, and evaluate their associations with resource use, complications, and mortality compared to admissions without these diagnoses. We evaluated congenital heart surgery admissions of ages < 18 years in the 1997, 2000, 2003, 2006, and 2009 Kids' Inpatient Database. Bivariate and multivariate analyses examined the adjusted association of trisomy 13 and 18 on resource use, complications, and inpatient death following congenital heart surgery. Among the 73,107 congenital heart surgery admissions, trisomy 13 represented 0.03% (n = 22) and trisomy 18 represented 0.08% (n = 58). Trisomy 13 and 18 admissions were longer; trisomy 13: 27 days vs. 8 days, p = 0.003; trisomy 18: 16 days vs. 8 days, p = 0.001. Hospital charges were higher for trisomy 13 and 18 admissions; trisomy 13: $160,890 vs. $87,007, p = 0.010; trisomy 18: $160,616 vs. $86,999, p < 0.001. Trisomy 18 had a higher complication rate: 52% vs. 34%, p < 0.006. For all cardiac surgery admissions, mortality was 4.5%; trisomy 13: 14% and trisomy 18: 12%. In multivariate analysis, trisomy 18 was an independent predictor of death: OR 4.16, 95% CI 1.35-12.82, p = 0.013. Patients with trisomy 13 and 18 represent 0.11% of pediatric congenital heart surgery admissions. These patients have a 2- to 3.4-fold longer hospital stay and double hospital charges. Patients with trisomy 18 have more complications and four times greater adjusted odds for inpatient death.

Role of Overexpressed Transcription Factor FOXO1 in Fatal Cardiovascular Septal Defects in Patau Syndrome: Molecular and Therapeutic Strategies.

Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis of PS first, followed by molecular analysis and docking studies. Thirty-seven PS cases were referred from the Department of Pediatrics, King Abdulaziz University Hospital to the Center of Excellence in Genomic Medicine Research, Jeddah during 2008 to 2018. Cytogenetic analyses were performed by standard G-band method and trisomy13 were found in all the PS cases. Studies have suggested that genes of chromosome 13 and other chromosomes are associated with PS. We, therefore, did molecular pathway analysis, gene interaction, and ontology studies to identify their associations. Genomic analysis revealed important chr13 genes such as FOXO1, Col4A1, HMGBB1, FLT1, EFNB2, EDNRB, GAS6, TNFSF1, STARD13, TRPC4, TUBA3C, and TUBA3D, and their regulatory partners on other chromosomes associated with cardiovascular disorders, atrial and ventricular septal defects. There is strong indication of involving FOXO1 (Forkhead Box O1) gene-a strong transcription factor present on chr13, interacting with many septal defects link genes. The study was extended using molecular docking to find a potential drug lead for overexpressed FOXO1 inhibition. The phenothiazine and trifluoperazine showed efficiency to inhibit overexpressed FOXO1 protein, and could be potential drugs for PS/trisomy13 after validation.

Mirror syndrome assocciated with patau syndrome: A case report / Síndrome de espelho associada a uma síndrome de Patau: um relato de caso

Abstract Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and/or placental hydrops. The disease can be life-threatening for both the mother and the fetus. The pathogenesis is poorly understood, and may be confused with preeclampsia, even though distinguishing features can be identified. We report a rare case of mirror syndrome with maternal pulmonary edema associated with fetal hydrops due to Patau syndrome.

Resumo A síndrome de espelho é uma patologia invulgar na qual o edemamaterno é observado em associação com hidropsia fetal e/ou placentária graves. Esta doença pode ser fatal paraamãe e para o feto. A sua patogênese émal compreendida, e pode ser confundida compré-eclâmpsia,mesmo comcaracterísticas distintivas identificadas. Relatamos um caso raro de síndrome de espelho com edema pulmonar materno associado a hidropsia fetal devido a síndrome de Patau.

Anesthesia in a child operated for cleft lip associated with Patau's syndrome / Anestesia em criança operada para lábio leporino associado à síndrome de Patau

Abstract Patients with Patau's syndrome (Trisomy 13) have multiple craniofacial, cardiac, neurological and renal anomalies with very less life expectancy. Among craniofacial anomalies cleft lip and palate are common. These craniofacial and cardiac anomalies present difficulties with anesthesia. We therefore describe the anesthetic management in the case of a Trisomy 13 child for operated for cleft lip at 10 months of age.

Resumo Os pacientes com síndrome de Patau (trissomia 13) apresentam várias anomalias craniofaciais, cardíacas, neurológicas e renais, com expectativa de vida bem menor. Entre as anomalias craniofaciais, o lábio leporino e a fenda palatina são comuns. Essas anomalias craniofaciais e cardíacas apresentam dificuldades na anestesia. Portanto, descrevemos o manejo anestésico em uma criança de 10 meses com trissomia 13 submetida à cirurgia de lábio leporino.

Adenocarcinoma and polyposis of the colon in a 20-year-old patient with Trisomy 13: a case report.

BACKGROUND: Trisomy 13 is one of the most common autosomal trisomies, and although increasing in number, patients surviving past the neonatal period remain rare. The natural history and expected complications in these patients as they age remains unknown. Despite the rarity of this condition, unusual malignancies have been reported in the medical literature for decades. It is clear that providers should suspect unusual malignancies in these patients, particularly as they age. CASE PRESENTATION: We report a 20-year-old Caucasian woman with Trisomy 13 who presented with colonic volvulus, found to have colonic polyposis and adenocarcinoma of the colon. Genetics of pathology specimens revealed 47(XX) + 13 without other mutations. She underwent prophylactic completion colectomy due to presumed risk of colorectal cancers given underlying adenomatous polyposis. She has recovered well without evidence of recurrence. CONCLUSIONS: The presence of colonic polyposis and colorectal cancer without family history or known mutations for polyposis syndrome suggests an intrinsic predisposition toward colorectal cancer in this patient with Trisomy 13. Recent research into colorectal cancer oncogenes supports that aneuploidy or increased copy number of certain genes on chromosome 13 may increase the risk of malignant transformation. This is an important correlation for researchers studying these topics and clinicians caring for patients with Trisomy 13 as they age.

Factors Influencing Outcomes After Cardiac Intervention in Infants with Trisomy 13 and 18.

Cardiac intervention remains controversial in patients with trisomy 13 and 18 and little is known about factors that may affect outcomes. The goal of this study was to evaluate preoperative factors and surgical approach with respect to outcomes in these patients. Patients with congenital heart disease and trisomy 13 or 18 presenting to our institution from 2004 through 2015 were retrospectively reviewed. Patients were grouped into complete intervention, palliated intervention, and non-intervention. Pre-intervention variables, timing and type of intervention, post-intervention outcomes, and survival were recorded and comparisons were made between the groups. Of 34 patients, 18 cardiac interventions were performed. Complete repair was performed in 11(61%) and palliation in 7(39%). Median age for complete repair was 9.2 vs. 1.7 months in palliated patients (p < 0.001) and palliated patients were smaller (median 2.5 vs. 5.2 kg, p < 0.001). All patients who underwent complete repair survived to discharge compared to only 57% of patients that were palliated (p = 0.04). Palliated patients had longer intubation and time to discharge (p < 0.05). Survival at last follow-up was greater in the complete repair group compared with palliated patients and non-intervention patients (72, 14, and 18%, p = 0.009) with a longer median length of survival in the complete repair group (p = 0.002). In our group of trisomy 13 and 18 patients, those able to undergo complete repair had improved outcomes. Patients undergoing complete repair were older and bigger; this suggests that delaying intervention and optimizing the likelihood of complete repair may be beneficial.

The Anesthetic Management for a Patient With Trisomy 13.

Trisomy 13 is a chromosomal disorder that occurs in complete or partial mosaic forms. It is characterized by central apnea, mental retardation, seizure and congenital heart disease. The survival of the patients with trisomy 13 is the majority dying before one month. Trisomy 13 is the worst life prognosis among all trisomy syndromes. It is reported the cause of death is central apnea. Special needs patients with mental retardation are recognized to have poorer oral health condition. Oral health related quality of life reflects daily activity and well-being. Dental treatment under general anesthesia is sometimes an option for such patients. This patient had received ventricular septal defect closure surgery at 2-year-old. In addition, he had mental retardation and seizure. Dental treatment had been completed without any cerebral and cardiovascular events under non-invasive monitoring with not only cardiac electric velocimetry, but also epileptogenic activity. In addition, postoperative respiratory condition was maintained stable in room air.