Congenital lung malformations: Dysregulated lung developmental processes and altered signaling pathways

Congenital lung malformations comprise a diverse group of anomalies including congenital pulmonary airway malformation (CPAM, previously known as congenital cystic adenomatoid malformation or CCAM), bronchopulmonary sequestration (BPS), congenital lobar emphysema (CLE), bronchogenic cysts, and hybrid lesions. Little is known about the signaling pathways that underlie the pathophysiology of these lesions and the processes that may promote their malignant transformation. In the last decade, the use of transgenic/knockout animal models and the implementation of next generation sequencing on surgical lung specimens have increased our knowledge on the pathophysiology of these lesions. Herein, we provide an overview of normal lung development in humans and rodents, and we discuss the current state of knowledge on the pathophysiology and molecular pathways that are altered in each congenital lung malformation.     

Congenital cardiovascular malformations: an intersection of human genetics and developmental biology

The practice of pediatric cardiology is poised to benefit from dramatic developments in human genetics and developmental biology. While clinicians have long known that congenital cardiovascular malformations arise as a result of disruption of the developmental process, it has taken decades to define the mechanisms. The combination of epidemiology, models of cardiovascular development in vertebrates, and the unprecedented understanding of the human genome has lead to new insights into ideology and pathogenesis. Expanded knowledge of Down's syndrome, cono-truncal defects, abnormalities of situs and looping, and Marfan syndrome, William's syndrome, and supravalvar aortic stenosis, Holt–Oram syndrome and Alagille syndrome, will allow clinical cardiologists to answer more precisely the three questions posed by parents: (1) will our child be all right; (2) what caused our child's heart defect; and (3) what about our other children and our grandchildren? This is the promise of the intersection of human genetics, developmental biology, and clinical pediatric cardiology.     

Congenital malformations and developmental changes of the breast: a neonatological view

Congenital malformations of the breast and nipple-areolar complex are described from the aspect of neonatal dysmorphology. Their classification is based on the accepted nomenclature in the medical literature and on a special method of clinical examination. The embryology and the possible genes involved in breast development are also discussed to clarify the mechanisms underlying the occurrence of breast malformations. Except for amastia, polymastia and polythelia, which have received much attention, the data for many other breast malformations are sparse. Case control studies or even case series are rare, and good evidence is often lacking. In addition, more studies are needed to complete the map of genes involved in breast development. This information will contribute substantially to our understanding and clinical approach to breast malformations in the future.     

先天性无肛畸形儿MR成像及其与排便功能关系研究

目的评估先天性肛门直肠畸形儿（anorectal malformations，ARM）尾端发育情况及横纹肌复合体（sphincter muscle complex，SMC）发育状态与排便功能的关系。方法39例ARM，男28例，女11例，应用不同序列体部相控阵列线圈或头部线圈MRI显示ARM直肠闭锁水平、骶尾椎、骶髓、泌尿生殖系的发育情况，并对SMC从多个层面进行定量分析，评估其发育状态与临床评分和肛门功能客观检查的关系。结果39例患儿中，MRI T1WI、T2WI扫描判断畸形水平的正确诊断率为100％，T2WI扫描瘘管检出率为96．9％。骶尾椎和骶髓的异常占41．0％，泌尿生殖系统畸形占20．5％。当耻骨直肠肌宽度的相对值PRWR〈0．18，外括约肌宽度的相对值EASWR〈0．15时，71．4％的ARM术后出现肛门失禁。当PRWR〉0．18，EASWR〉0．15时，91．3％的ARM术后排便功能好。结论MR检查能清楚地显示ARM类型、闭锁水平、SMC发育状态、脊柱脊髓及泌尿生殖系统存在的伴发畸形，从MR影像中找到了评价SMC的定量指标。     

Congenital bronchopulmonary foregut malformations: concepts and controversies

This article addresses the scope, etiology, important associations and imaging features of congenital bronchopulmonary foregut malformations. Etiologic concepts, including airway obstruction and vascular anomalies, are highlighted. Technical imaging advances, especially CT and MR, have greatly enhanced our diagnostic abilities in evaluating these lesions; however, thorough and careful assessment of all aspects of the malformation is still necessary. Several specific lesions are discussed in more detail, particularly regarding controversial issues in classification, understanding, imaging and management.     

Congenital heart defects--chromosomal anomalies, syndromes and extracardiac malformations

AIM: To register chromosomal anomalies, syndromes and extracardiac malformations in patients with Congenital heart defects (CHDs). METHOD: Population-based prospective observational study. RESULTS: Of 57 027 live births during 1982-2005, CHDs were detected in 662 (11.6 per 1000), of whom 146 (22%) had associated anomalies. Of these 52 (36%) had chromosomal anomalies (exclusive microdeletions), 26 (18%) genetic syndromes/microdeletions, 1 (0.7%) a teratogenous syndrome and 67 (46%) extracardiac malformations. In perimembraneous ventricular septal defects (VSDs), associated anomalies occurred in 22 of 70 (31%) compared to 27 of 298 (9%) in VSDs located in the muscular part of the septum (p < 0.0001). The prevalence of CHDs with associated disorders increased significantly from the cohort born during 1982-1993 to those born during 1994-2005 (2.0 vs. 3.1 per 1000, respectively; p < 0.0001), mainly caused by an increase of chromosomal trisomies (0.5 vs. 1.1 per 1000; p = 0.026). The percentage of women giving live birth at 35 years of age or more was 7.6% for the period 1982-1993 compared to 13.4% for 1994-2005 (p = 0.001). CONCLUSIONS: Chromosomal anomalies, syndromes and extracardiac malformations occurred in nearly one-fourth of CHD cases. Muscular VSDs had a low prevalence of such conditions. The prevalence of CHDs with chromosomal trisomies increased, and was probably related to an increasing age of women giving birth.     

Congenital malformations in Kumasi,Ghana: prognosis for surgical cases

One hundred sixty-one cases of congenital anomalies admitted to the special ward for sick children over a period of 4 years have been analyzed with regard to incidence of individual diagnoses, age at admission, place of delivery, and overall and postoperative mortality. The malformations involved the abdomen, gastrointestinal and digestive systems (40.4%), head and neck (19.9%), vertebral column and extremities (28.0%), and urinogenital system (6.2%). The most frequent were anorectal malformations (26.7%), followed by cleft lip and cleft palate (14.3%), spina bifida (13.7%), exomphalos (9.3%), and talipes (7.5%). In all, 143 cases (88.8%) should have been amenable to surgery, but only 86 (53.4%) were operated upon. An overall high mortality (33.5%) was attributed to places of delivery with inadequate medical facilities, delayed referral to more competent health institutions, poor general condition of the patients, associated anomalies, and complications. Postoperative mortality was also high for the same reasons. Institution of specific registry or monitoring programs and improvement of medical facilities is recommended to enhace the prognosis for children with congenital malformations. Offprint requests to: D. nii-Amon-Kotei     

Congenital primary cerebral angiosarcoma: CT,US, and MR findings

Congenital primary intracranial angiosarcoma (CAS) is an exceptionally rare tumor. To our knowledge the imaging features of intracranial angiosarcomas have only been briefly mentioned in the neuropathologic literature. To our knowledge, only one case of CAS has been reported. We present a case of a pathologically proven CAS found in a neonate.     

Congenital heart disease: Genetic causes and developmental insights

The genetic basis of congenital heart disease, an important form of cardiovascular disease in the young, is being increasingly recognized. Using a combination of human molecular genetic studies and developmental models in several animal species, significant advances in the understanding of normal cardiac development and the pathogenesis of cardiac malformations are being made. Here we review congenital heart disease due to single gene defects identified by human genetic studies, genotype–phenotype correlations and insights into pathogenesis resulting from studies in model systems. The future promises that these complementary approaches will inform clinical management and provide the means to develop new diagnostic and therapeutic approaches to congenital heart disease.     

Spinal dysraphic anomalies; classification,presentation and management

Spinal dysraphism comprises an array of congenital anomalies of spinal cord development. Each of the dysraphic disorders can result in neurological, orthopaedic and urological dysfunction. This potentially confusing array of conditions is best understood from the embryological perspective. Whilst not all of these conditions are managed in the same way similar principles govern the initial investigation, multidisciplinary evaluation and long term follow up of these cases.     

Congenital high airway obstruction syndrome: MR/US findings, effect on management, and outcome

Background  Congenital high airway obstruction syndrome (CHAOS) is a rare disorder defined as any fetal abnormality that obstructs the larynx or trachea. Prompt airway intervention at delivery after accurate prenatal diagnosis may allow survival of this otherwise fatal condition. Objective  To identify prenatal MRI findings in CHAOS, to compare these findings with those of fetal US, to determine if imaging alters diagnosis and management decisions, and to correlate prenatal with postnatal imaging findings. Materials and methods  Records and MRI scans of ten fetuses with CHAOS were reviewed, and the findings correlated with outside and same-day fetal US and postnatal imaging findings. Fetal lung volumes were measured on MRI scans. Results  Large lung volumes were found in 90% of the fetuses. Increased lung signal intensity, inverted diaphragm, and a dilated, fluid-filled lower airway were identified in all. The obstruction level was identified in 90%. MRI changed screening US diagnosis in 70%, but was concordant with the tertiary care US imaging in 90%. Seven fetuses were terminated or died in utero, and three fetuses survived after ex utero intrapartum tracheostomy placement. Autopsy or bronchoscopy performed in 60% confirmed CHAOS. Postnatal chest radiographs and CT showed hyperinflation, while US and fluoroscopy showed diminished diaphragmatic motion. Conclusion  MRI demonstrates large lung volumes, increased lung signal intensity, inverted diaphragm, and dilated fluid-filled lower airway, and usually identifies the obstruction level. The degree of correlation between MRI and tertiary prenatal US is high, but CHAOS is frequently misdiagnosed on screening US. Correct diagnosis may enable planned airway management. Voluminous lungs and diaphragmatic abnormalities persist on postnatal imaging.     

Congenital vaginal obstructions: varied presentation and outcome

Congenital obstructing lesions of vagina, hydrometrocolpos, and hematocolpos, present at a variable time during early childhood and adolescence to different medical and surgical specialties. Twenty-six cases presenting over an 18-years period (1987–2005) were divided into three groups; Group A: neonates (6), Group B: adolescents (18), and Group C: adults (2). Common presentations in neonates (Group A) were abdominal mass (5), neonatal sepsis (3), and respiratory distress (2); whereas abdominal pain (18), voiding dysfunctions (13), and backache (7) were prevalent in adolescents (Group B). Adults (Group C) presented with inability to consummate and infertility (2). Four patients received erroneous treatment; exploratory laparotomy (1) and appendectomy (3). Urinary symptoms and associated urinary abnormalities were present in more than 50% of cases, especially those with complex anomalies. Management included excision of imperforate hymen (16) and transverse vaginal septum (8) through perineal (20) and abdominoperineal approach (4). Patients with urogenital sinus (1) and cloacal malformation (1) had staged reconstruction at 2.5 years of age following preliminary vesicostomy and colostomy at birth. On follow up (range 1–15 years; mean 7) more than 60% patients have menstrual irregularity (11), endometriosis (5), and infertility (4). In conclusion, rarity and variable presentation of congenital vaginal obstructions can lead to delayed diagnosis and erroneous management. A high index of suspicion and cross-sectional imaging help in early diagnosis and associated renal anomalies. A comprehensive management is imperative to preserve the reproductive potentials, as significant proportion of patients may experience sexual difficulties, menstrual irregularity, and infertility.     

Congenital epulis: prenatal imaging with MRI and ultrasound

Congenital epulis is an uncommon benign tumor that originates from the alveolar ridge in newborns. It is also known as congenital gingival granular cell tumor. Although there have been around 200 reports of its postnatal diagnosis, this oral tumor has rarely been diagnosed prenatally. We present fetal MRI and Doppler prenatal imaging of an infant with two congenital epulides (simultaneous involvement of superior and inferior maxillas).     

Congenital Rosai–Dorfman disease presenting with anemia,thrombocytopenia, and hepatomegaly

Rosai–Dorfman disease (RDD) is a rare entity of non‐Langerhans cell histiocytoses (non‐LCH) which usually presents with bilateral painless cervical lymphadenopathy. We describe a neonate with RDD who presented with anemia, thrombocytopenia and hepatomegaly. He recovered spontaneously with conservative management. This represents an atypical presentation of RDD. Conservative management with close monitoring can be adopted for some with systemic involvement. Pediatr Blood Cancer 2009;52:415–417. © 2008 Wiley‐Liss, Inc.     

CAMT in a female with developmental delay, facial malformations and central nervous system anomalies

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder characterized by thrombocytopenia and absence or decline in the number of megakaryocytic precursors in the bone marrow. It is caused by mutations in the thrombopoietin receptor gene, c-mpl, involved in the proliferation and differentiation of megakaryocytes and platelets. The association between CAMT and central nervous system (CNS) anomalies has been reported in the literature, albeit not very frequently. Here we present a unique case where CAMT appeared associated to cerebellum agenesis, hypoplasia of the corpus callosum and brainstem, facial malformations, and developmental delay.     

Transport,monitoring, and successful brain MR imaging in unsedated neonates

Neonatal cerebral MR imaging is a sensitive technique for evaluating brain injury in the term and preterm infant. In term encephalopathic infants, MR imaging reliably detects not only the pattern of brain injury but might also provide clues about the timing of injury. In premature infants, MR imaging has surpassed US in the detection of white matter injury, a common lesion in this population. Concerns remain about the safety and transport of sedated neonates for MR examination to radiology suites, which are usually located at a distance from neonatal intensive care units. We present our own institutional experience and guidelines used to optimize the performance of cerebral MR examinations in neonates without sedation or anesthesia.     

Popliteal cysts in children: prevalence, appearance and associated findings at MR imaging

Objective. The purpose of this study was to determine the prevalence of Baker's cysts on MR images in a paediatric orthopaedic population, to investigate the association of Baker's cyst with joint fluid and joint disorders in children, and to compare the MR appearance of Baker's cysts in children with that previously reported in adults. Materials and methods. Reports from 393 MR studies of the knee performed in children aged from 1 to 17 years were retrospectively reviewed for the presence of a Baker's cyst, joint effusion, meniscal tear, anterior cruciate ligament tear, or any other joint disorder. Results. A Baker's cyst was identified in 6.3 % (25/393) of patients. The MR images and clinical charts of patients with a Baker's cyst were reviewed. None of the 25 patients with a Baker's cyst had an associated anterior cruciate ligament tear or meniscal tear. Two patients had osteochondritis dissecans and two others had synovial disease (infection and juvenile rheumatoid arthritis). Joint fluid was demonstrated in 16 % (4/25) of patients with a Baker's cyst. There was no statistically significant association between presence of a Baker's cyst and presence of joint fluid. Conclusions. Baker's cyst is less prevalent in a paediatric orthopaedic population than in an adult population. In children, it seems that Baker's cyst is seldom associated with joint fluid, meniscal tear, or anterior cruciate ligament tear. On MR images, a communication between the Baker's cyst and the joint was not demonstrated in any of the patients. In addition, the presence of debris and cyst leakage was not observed. Received: 20 August 1998 Accepted: 15 February 1999     

Ticks and tick paralysis: imaging findings on cranial MR

Tick paralysis is an acute, progressive, and potentially fatal muscle paralysis secondary to a toxin secreted by a pregnant tick during a bite. Although tick bites can occur anywhere on the body, ticks are frequently overlooked on the scalp because of overlying hair. Children with acute neurologic symptoms frequently undergo MR scanning that may incidentally reveal the offending tick. Timely identification and removal of the tick leads to rapid recovery from tick paralysis. We report the MRI findings at 1.5 T of tick paralysis with an attached tick.