Clinical Characteristics and Genetic Analysis of Klippel-Feil Syndrome / 中国医学科学院学报

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.

Hernia of the umbilical cord: a clinical spectrum

Background: Hernia of the umbilical cord is a rare clinical entity which presents with hernia of the small bowel into the proximal part of the umbilical cord. This is sporadically associated with other congenital malformations. This is usually poorly identified and mistakenly termed as 'omphalocele minor. Inadvertent clamping of the cord in these cases leads to iatrogenic bowel wall injury. The aim of this study is to present a spectrum of cases presenting with umbilical cord hernia in a tertiary care Govt medical college, along with demography, intra operative findings, associated malformations and postoperative outcome and 1 year follow up.Methods: This is an ambispective study on neonates who attended the Outpatient Department (OPD) or Emergency department. The babies were evaluated by age, birth weight, gender, any gross clinical malformation. They were also evaluated intraoperatively for any associated anomalies. Post-surgery the babies were followed up until 2 years of age in pediatric surgery OPD of the same institute and outcome was recorded.Results: Out of 90 babies, 88 babies (97.77%) had body weight more than 2.5 kg, and rest 2(2.22%) had bodyweight of 1.5kg and 1.8 kg. Regarding content of contents of umbilical cord hernia, out of 87 patients, 43 patients (49.42%) had ileal loop as, 32 patients (36.78%) had ileum with Meckel's diverticulum, 6 patients (6.39%) had cecum with appendix.Conclusions: Most of this study cases had ileal loops as content of the hernial sacs, and 36.78% cases had Meckel's diverticulum associated, which is a remnant of Vitello intestinal duct. Prompt identification of the condition and early intervention and adequate post-natal care are affective to prevent long term morbidity.

La supervivencia en neonatos con afecciones complejas en Cirugía Pediátrica / Neonates' survival from complex conditions after Pediatric Surgery

RESUMEN Introducción: el análisis de supervivencia es uno de los métodos estadísticos más empleado en los estudios clínicos. Objetivo: determinar la influencia de factores de riesgo en la supervivencia de los neonatos con afecciones complejas en Cirugía Pediátrica. Método: en este trabajo se estudiaron los pacientes atendidos en el Centro Regional de Cirugía Neonatal de Holguín, desde el 1ro de enero de 1994 hasta el 31 de diciembre del 2015. El universo estuvo constituido por 382 niños y la muestra por 295, con un tiempo de seguimiento de hasta 28 días. Se analizaron las variables como: peso al nacer, edad gestacional y anomalías asociadas; según los factores de riesgo como: bajo peso al nacer, neonato pretérmino y anomalías asociadas; así como su influencia en la supervivencia. Con la ayuda del paquete estadístico SPSS versión 15 sobre Windows XP, se efectuó el análisis de las curvas de supervivencia por el método Kaplan-Meier, y los factores de riesgo por el método Log-Rank. Resultados: del total de la muestra (n=295), se obtienen 66 neonatos con nacimiento pretérmino (22,4%), 82 con bajo peso al nacer (27,8%) y 154 con anomalías asociadas (52,2%); siendo este el factor de riesgo predominante. En dichos pacientes, se aprecia un alto número de eventos con influencia en su supervivencia, durante el seguimiento del período neonatal. El evento final ocurrió en 61 neonatos (20,7%). La media en el tiempo de supervivencia de los neonatos con afecciones complejas en Cirugía Pediátrica fue de 23 días. Conclusiones: en la supervivencia de los pacientes influyeron los factores de riesgo estudiados. La sepsis severa fue la causa directa de muerte que predominó.

ABSTRACT Introduction: survival study is one of the most used statistical methods in the clinical field. Objective: to determine the influence of risk factors over neonates´ survival form complex conditions after Pediatric Surgery. Method: in this work we studied patients attended in the Regional Center of Neonatal Surgery of Holguín, from January 1st, 1994 to December 31st, 2015. Universe was 382 neonates and the sample was 295, monitored during 28 days. Analyzed variables were: birth weight, gestational age and associated anomalies; according to its risk factors like: low birth weight, preterm neonates and associated anomalies, as well as their influence on neonates 'survival. By the use of statistical package SPSS version 15 on Windows XP, survival curves were analyzed by the Kaplan-Meier method and the risk factors by Log-Rank. Results: of the total sample (n=295) 66 neonates were preterm births (22.4%); 82 low birth weight (27.8%) and 154 showed associated anomalies (52.2%) as the main risk factor. Patients studied showed high numbers of events and their influence on survival during neonatal period. The final event occurred to 61 neonates (20.7%). Conclusions: risk factors studied were influenced by patients´ survival and the direct cause of death was severe sepsis.

Displasia renal multiquística, ¿tratamiento conservador o nefrectomía?: is it appropriate to follow the conservative treatment or nephrectomy? / Multicystic renal dysplasia

Introducción: la displasia renal multiquística es una anomalía relativamente frecuente en la que aún se mantienen algunas discrepancias en la conducta médica a seguir. Objetivos: analizar la evolución de los quistes en un grupo de pacientes con diagnóstico prenatal de esta anomalía, en los que se siguió una conducta médica conservadora y expectante. Métodos: durante el período comprendido entre el 1º de enero de 1996 y el 30 de junio de 2011, se recibieron en la consulta de Nefrología del Hospital Pediátrico Universitario "William Soler", 22 recién nacidos o lactantes, en los que, durante el seguimiento de un embarazo normal, se diagnosticó una displasia renal multiquística u otra anomalía, que al estudiarse después del nacimiento, se demostró la displasia. En todos los pacientes se realizó ultrasonido renal al llegar al hospital y se hizo gammagrafía estática (99m tecnecio-DMSA) para precisar función renal del lado afectado y valorar las características del riñón contralateral. En todos los casos se siguió una conducta conservadora y expectante, y en 21 de estos niños se logró el objetivo de este estudio. Resultados: hubo predominio del sexo masculino en 60 %, del riñón izquierdo en 77 % y la forma "típica" de displasia en el 80 %. En 6 pacientes se encontraron otras anomalías asociadas. En 3 fetos se presentó involución prenatal de los quistes, la involución total entre 3 y 72 meses se observó en 9 (50,0 % de los estudiados después del nacimiento), mientras hubo involución parcial en 6 (33,3 %) y no hubo variación en 3 (16,7 %). Conclusiones: el tratamiento conservador debe ser la elección inicial en todo paciente con displasia renal multiquística, ya que la involución total se logra en la mayoría de los casos en un período relativamente corto.

Introduction: multicystic renal dysplasia is a relatively frequent anomaly that still arouses some discrepancies about the medical behaviour to be followed. Objectives: to analyze the evolution of cysts in a group of patients prenatally diagnosed with this anomaly, with whom a conservative and expectant medical behaviour was adopted. Methods: from January 1st, 1996 to June 30th, 2011, the nephrology service of "William Soler" university pediatric hospital assisted 22 newborns and infants, who were diagnosed with multicystic renal dysplasia or other anomaly during the normal pregnancy follow-up, but later dysplasia was confirmed after birth. All these patients underwent renal ultrasound on arrival at hospital, and then static gammagraphy (99m technetium-DMSA) to see the renal function of the affected side and to assess the characteristics of the contralateral kidney. A conservative and expectant behaviour was observed for all the cases; the objective of this study was attained in 21 of these children. Results: males prevailed in 60 % of patients, left kidney was affected in 77 % of cases and the "typical" form of dysplasia was present in 80 % of them. Six infants presented with other related anomalies. There was prenatal regression of cysts in three children, total regression ranging 3 to 72 months in 9 infants (50 % of the infants under study after birth) whereas partial regression occurred in 6 cases (33.3 %) and 3 did not change their condition (16.7 %). Conclusions: the conservative treatment should be the initial choice for every patient with multicystic renal dysplasia since total regression is possible in most of cases in a relatively short period of time.

Clinical characteristics and perinatal outcomes of fetal omphalocele / 대한산부인과학회지

OBJECTIVE: The purpose of this study is to describe the clinical characteristics and perinatal outcomes of fetuses with omphalocele. METHODS: The study enrolled all fetuses diagnosed prenatally with omphalocele at a single institution, from August 1996 to April 2008. Data were collected retrospectively by reviewing the maternal and neonatal medical records. RESULTS: The study population consisted of 54 cases with prenatally diagnosed omphalocele. In all, 15 fetuses were live-born, 29 were terminated, four died in utero, and six were lost to follow-up. Associated anomalies were found in 72.9% (35/48). Abnormal karyotype was found in 33.3% (16/48). In the live births, associated major anomalies were present in 46.7% (7/15) and were associated with increased neonatal morbidity. The rate of severe neonatal morbidity was 53.3% (8/15). In one case, death followed prolonged hospitalization with complications related to associated anomalies. The neonatal mortality rate was 6.7% (1/15) with no postoperative deaths. CONCLUSION: In this study, the neonatal mortality rates were low in the absence of associated anomalies or genetic defects. The results emphasize the importance of identifying both those fetuses with a potentially positive prognosis and favorable outcome and those which are likely to have a fatal outcome.

Sacral Agenesis in Children: 15 Year Experiences

PURPOSE: Sacral agenesis may occur as an isolated lesion or in conjunction with other syndromes of caudal regression. Patients with disorder often have varying degrees of vesical dysfunction. Our longitudinal experience with cohort of patients with sacral agenesis provides the model for clinimetrics in care of children with congenital anomalies. MATERIALS AND METHODS: Between 1984 and 1998, we evaluated 33 children(18 boys, 15 girls) with sacral agenesis. All patients were evaluated with renal ultrasound, cystometrogram, and voiding cystourethrogram. RESULTS: The age at initial evaluation ranged from newborns to 18 years of age, with a mean age of 5.5 years. The follow-up period ranged from 1 week to 14 years, with a mean of 7.2 years. Associated genitourinary anomalies were present in 23 patients. Only four children had no associated anomalies. And then 27 patients have maintained native bladder while 6 children underwent surgery for small bladder. Urinary continence was evaluated in 27 patients. Twenty-one patients are complete or partial dry on intermittent catheterization ; 6 patients are managed with pull-ups; none showed normal voiding. Of the 31 patients where pressure based bladder capacity could measured, only 3 patients had age expected bladder capacity; all others had an average of 56% below the age expected bladder capacity. Most patients have maintained stable renal function and renal growth. Two patients had scarring to the refluxing units with one eventually requiring nephrectomy for chronic infection. CONCLUSION: Our experience illustrates that sacral agenesis patients have a high incidence of associated genitourinary and anorectal anomalies. Continence may be achieved with clean intermittent catheterization. The outcomes of consistent upper tact preservation and absence of high-pressure bladder suggest that sequential urodynamic evaluation can be streamlined.

Types and Associated Anomalies of Congenital Scoliosis / 대한척추외과학회지

STUDY DESIGN: Analysis was based on radiographic appearance of 57 cases of congenital scoliosis and associated anomaly PURPOSE: The aim of the present study was to assess the incidence, morphology and the associated anomalies of the congenital spinal scoliosis. SUMMARY OF LITERATURE REVIEW: Hemivertebra is the most common type of congenital scoliosis and urogenital, musculoskeletal and cardiac anomalies are strongly associated. MATERIALS AND METHODS: The authors analysed the morphology and the associated anomalies of 57 cases of congenital scoliosis from 1994 to 2000. RESULTS: It was more common in male(32 males and 25 females). The bony anomalies were classified as failure of formation(40cases, 70.2%), failure of segmentation(11cases, 19.3%) and mixed type(6cases, 10.5%). Of the failure of formation, there were 36 cases(63.2%) of hemivertebra, 2 cases of posterior quadrant vertebra and 2 cases of wedge vertebra. We found associated anomalies in 26 patients(45.6%). Associated cardiac anomalies were 2 dextrocardia, ventricular septal defect, atrial septal defect and patent ductus arteriosus. Associated musculoskeletal anomalies were 5 rib fusion, 2 developmental dysplastic hip, 3 Klippel-Feil syndrome, Achondroplasia, Arnold-Chiari malformation, spinal dysraphism with sacral hair patch, cleft palate with congenital anklyloglossia. Associated neurogenic anomalies were 2 cases of syringomyelia and 3 mental retardation. There were unilateral renal agenesis and undescended testicle in urogenital anomalies. CONCLUSIONS: Common type of the congenital scoliosis was hemivertebra(63.2%) caused by the failure of formation(70.2%). Associated anomalies were found in 26 patients(45.6%).

Clinical Feature and Prognosis of Pregnancies with Fetal Gastroschisis / 대한산부인과학회잡지

No abstract available.

Clinical Study on Neonatal Gastrointestinal Obstructions

PURPOSE: Neonatal surgical conditions affecting the gastrointestinal tract are varied, can affect any part of the intestinal tract, and frequently require urgent surgical intervention. Unfortunately, nonspecific and overlapping symptomatology exists among the conditions affecting the intra-aMominal intestinal tract and requires of the evaluating physician a thorough understanding of their pathophysiology. So we studied signs and symptoms, frequency and incidence, ages at diagnosis, and diagnostic method of the neonatal gastrointestinal obstructions. METHOD: We reviewed retrospectively the charts of patients, who had been diagnosed as gastrointestinal obstruction during the neonatal period, and had been admitted to Gyeongsang National University Hospital from Feb. 1988 to Feb. 1997. RESULT: Total 77 cases were enrolled in this study. There were 59 rnales (76.796) and female 18 cases (23.4%). The male to female ratio was 3.28: 1. Twenty-two cases of imperforate anus (28.6%), 18 cases of hypertrophic pyloric stenosis (23.4%), 15 cases of congenital megacolon (19.5%) were observed. Other diseases causing the neonatal gastrointastinal obstruction were annulus pancreas (7.8%), jejunal atresia (6.5%), duodenal atresia (1.3%), duodenal web (2.6%), ileal atresia (2.6%), midgut volvulus (2.6%), intussusception (1.3%), and trachoesophageal fistula (2.6%). The rnost common symptom was vomiting with 32 cases (41.6%), followed by abdominal distension with 31 cases (40.3%), absence of anus with 17 cases (22.1%), and delayed meconium passage with 9 cases (11.7%). Associated other anomalies were observed in 18 cases (23%). Imperforate anus was seen with the highest rate of associated anomalies. The most common associated anomaly was the cardiac anomaly. Colon study (26%), physical examination (24.7%), abdominal sonography (15.6%), upper GI series (11.7%), and simple abdomen (9.1%) were diagnostic in the neonatal gastrointestinal obstructions. Seventeen cases (22%) were died before or after the surgical intervention. CONCLUSION: Neonatal gastrointestinal obstructions were associated with the high mortality rate. Abdominal distension and vomiting were the specific symptoms of neonatal gastrointe- stinal obstructions. Extensive search for the associated anomalies are reqiured because of its high frequency in the patients of the neonatal gastrointestinal obstructions. Thorough physical examination, colon study, abdominal sonography, upper GI series, and simple abdomen were essential in the diagnosis of the neonatal intestinal obstructions.

Aqueductal Atresia with Forking Anomaly: Report of 3 cases

Aqueductal forking was first described by Russell (l949) as a cause of aqueductal obstruction and a form of congenital malformation with simple stenosis, it is a relatively common cause of congenital hydrocephalus not associated with spina bifida or meningomyelocele. Pathologically it is characterized by two distinct channels separated by non-gliotic brain tissue. We describe variable clinicopathologic findings of 3 autopsy cases showing hydrocephaly due to aqueductal atresia with forking case 1 was a 35-week-old female showing Potter's syndrome, dextrocardia, and skeletal anomaly. case 2 was a 29-week-old male abortus with micrognathia, simian crease, club feet, and minor defects of visceral organs. Case 3 was a 32-week-old female abortus with associated anomalies such as a low-set ear, ectopic thymus and thyroid, and Meckel's diverticulum. On serial sections of brain stems of all 3 cases, were seen variably shaped and atretic lumina of aqueducts with distinct two channe1s and intervening brain tissues of normal cellularity.