New diagnostic and therapeutic procedures applied in pediatric esophageal achalasia in a pediatric tertiary center: A case series.

Achalasia is an esophageal motor disorder that is rare in children. While the condition is uncommon, it is especially difficult to diagnose in pediatric patients; however, the ability to form a diagnosis has progressed markedly with the advent of esophageal high-resolution manometry (HRM). The aim of the present study was to highlight particularities of the diagnosis, based on esophageal HRM, as well as the treatment of achalasia in children. The current study analyzed cases of achalasia from a single pediatric tertiary center, Clinical Emergency Hospital for Children (Cluj-Napoca, Romania). The clinical data and the results of the investigations of seven children with achalasia, the first children to be evaluated using esophageal HRM in the center, were reported. The patients were aged between 11 and 18 years. All the patients were newly diagnosed with achalasia, except for one. The duration of symptoms was between 4 months and 2 years in the newly diagnosed patients. All the patients were assessed with conventional esophageal manometry and/or esophageal HRM. A multidisciplinary team contributed to the diagnosis and the management of achalasia. A total of 4 children diagnosed with type II achalasia were treated with peroral endoscopic myotomy (POEM) and 3 of the patients were treated with pneumatic dilations. Overall, achalasia is a rare but challenging condition in children. A diagnosis starts with a clinical suspicion based on swallowing disorders and upper digestive endoscopy, and is confirmed by esophageal HRM. Therapy should be adapted to the type of achalasia, the age of the children and the severity. In the present study, a relatively recent treatment option, POEM, was applied in pediatric patients with minor immediate adverse events. The report of these cases adds to the limited experience of using HRM and POEM in children with achalasia.

Diagnosis and Management of Genetic Causes of Middle Aortic Syndrome in Children: A Comprehensive Literature Review.

Middle aortic syndrome (MAS) is a rare vascular disease representing an important cause of severe hypertension in children. MAS is characterized by segmental or diffuse narrowing of the abdominal and/or distal descending aorta with involvement of the renal and visceral branches. Most cases of MAS are idiopathic, but MAS may occur in genetic and acquired disorders. The most common genetic causes of MAS are neurofibromatosis type I, Williams syndrome, Alagille syndrome, tuberous sclerosis and mucopolysaccharidosis. This review article discusses the pathophysiological aspects, distinctive associated features, and management of genetic forms of MAS in children.

Diagnostic, treatment and outcome possibilities in achondroplasia.

INTRODUCTION: Achondroplasia is a common form of chondrodysplasia. It is transmitted by autosomal dominant trait. The disease is determined by mutations in receptor-3 gene of the fibroblast growth factor. The most frequent mutations are c.1138G>A and c.1183G>C; c.1138A. The diagnosis can usually be made on the basis of clinical characteristics and specific features on radiographs. It is not necessary to perform molecular testing in every child with a clinical diagnosis of achondroplasia.The aim of this study is to establish the diagnostic, treatment and outcome possibilities in patients with achondroplasia in our care. METHOD: The study group consisted of 27 patients with achondroplasia. The method consisted of: clinical and radiological examinations. The DNA analasys was performed by PCR-RFLP technique. RESULTS: 80 patients were diagnosed with bone dysplasia; 24 of them were diagnosed (on clinical and radiological basis) with achondroplasia. Out of this group, 16 patients were identified as heterozygotes for G1138A mutation in FGFR3 gene; 3 patients undergoing treatment with somatotropic hormone; the growth rate is improving from 0.1 cm/month to 0.5 cm/month. CONCLUSIONS: In achondroplasia diagnosis is based on clinical and radiological criteria. It is the first study that reports the prevelance of this mutation in Romania.

Cardiac Manifestations in a Group of Romanian Patients with Gaucher Disease Type 1 (a Monocentric Study).

Gaucher disease (GD), one of the most common lysosomal disorders, is characterised by clinical heterogeneity. Cardiac involvement is rare and refers to pulmonary hypertension (PH), valvular abnormalities and myocardial infiltrative damage. The aim of this study was to evaluate cardiac involvement in a group of Romanian GD patients. Phenotypic and genotypic characterisation was carried out in 69 patients with GD type 1. Annual echocardiography and electrocardiography were performed to assess pulmonary pressure, morphology and function of the valves and electrocardiographic changes. Nine patients (13%) exhibited baseline echocardiographic signs suggesting PH. Mitral regurgitation was present in 33 patients (48%) and aortic regurgitation in 11 patients (16%). One patient presented aortic stenosis. Significant valvular dysfunction was diagnosed in 10% of patients. PH was associated with greater age (p < 0.001), longer time since splenectomy (p = 0.045) and longer time between clinical onset and the start of enzyme replacing therapy (p < 0.001). Electrocardiographic changes were present in five patients (7%).

Skeletal Abnormalities and VDR1 Gene Polymorphisms in Mucopolysaccharidosis Patients.

INTRODUCTION: Articular and bone damage, which is so disabling in Mucopolysaccharidosis (MPS), requires attention as to the explanatory bias of the pathogenetic mechanisms identified to date. The vitamin D receptor (VDR) has been investigated in many studies in correlation with bone metabolism, osteoporosis, and the impaired bone mineral density associated with certain polymorphisms of the VDR gene. AIM: This study aims to observe whether there is an association between clinical features, phospho-calcium metabolism parameters and the VDR gene polymorphisms in patients with MPS. PATIENTS AND METHOD: We evaluated six patients with MPS type I, 20 patients with MPS type II, two patients with MPS types IIIA and IIIB and three patients with MPS type IVB. In these patients, phospho-calcium metabolism, markers of bone formation, bone radiographs and bone densitometry were evaluated, as were four polymorphisms of the VDR gene (ApaI, BsmI, FokI and TaqI). RESULTS: There was a deficiency in 25 hydroxy vitamin D in MPS type I patients at the final evaluation and in MPS type II patients, both at ERT initiation and at the last evaluation. The analysed polymorphisms were not associated with modified calcium-phosphor levels, but some differences were observed regarding the level of 25 OH vitamin D. Thus, in the case of AA polymorphism, all patients have a 25 OH vitamin D deficiency, and one patient with the AA genotype and three with Aa have a 25 OH vitamin D deficiency and secondary hyperparathyroidism due to this deficiency (four patients), all of them having the Bb phenotype. CONCLUSION: In MPS patients, vitamin D deficiency is observed, as it is in some patients with secondary hyperparathyroidism, which indicates vitamin D supplementation to protect bone metabolism. There are no obvious correlations between VDR polymorphism and bone metabolism in MPS patients.

The value of abdominal ultrasonography compared to colonoscopy and faecal calprotectin in following up paediatric patients with ulcerative colitis.

AIM: To evaluate the value of abdominal ultrasonography (US) in the follow-up of paediatric patients with ulcerative colitis (UC) compared to faecal calprotectin (FC) and colonoscopy. MATERIAL AND METHOD: In this retrospective study we enrolled 30 paediatric patients previously diagnosed with UC, examined by abdominal US and colonoscopy within the same week. FC was also determined during the same week. Disease activity was established using the paediatric ulcerative colitis activity index (PUCAI). The global endoscopic activity was evaluated using the Mayo endoscopic subscore. RESULTS: Endos-copy revealed pathological findings of active disease in 27 out of 30 patients; 3 patients were in endoscopic remission. Only 18 of them had clinical active disease (PUCAI >10), [sensitivity (Se) 66.7% and specificity (Sp) 33% of PUCAI in detecting endoscopic active disease). Twenty-three (76.7%) patients had FC >250 mcg/g, but in 2 of these cases the colonoscopy was normal (Se 77.8% and Sp 33.3% in detecting active disease). At US examination, pathological findings (increased bowel wall thickness, hypervascularity, lymphadenopathies, and/or mesenteric inflammatory fat) were found in 27 patients (90%), all with endoscopic active disease (agreement US - colonoscopy, at patient level, k=1.0, p<0.001, Se 100% and Sp 100%). At seg-ment level (totally 180 bowel segments examined by US), the overall agreement between US and colonoscopy was k=0.767, p<0.001, Se 86.5%, Sp 90.1%. Of the 27 patients with US pathological findings in any of colonic segments, 23 had FC >250 mcg/g (85.1%). The inter-observer agreement for the US measurements had an overall ICC of 0.926 with p<0.001. CONCLUSION: Abdominal US findings demonstrate a good to excellent concordance with endoscopic examination and are correlated with elevated FC levels. Therefore, US appears as an accurate technique in assessing activity in patients with UC and might replace colonoscopic evaluation for the follow-up.

16q24.3 Microduplication in a Patient With Developmental Delay, Intellectual Disability, Short Stature, and Nonspecific Dysmorphic Features: Case Report and Review of the Literature.

We describe the case of a seven-year-old female patient who presented in our service with severe developmental delay, intellectual disability, facial dysmorphism, and femur fracture, observed in the context of very low bone mineral density. Array-based single nucleotide polymorphism (SNP array) analysis identified a 113 kb duplication involving the morbid OMIM genes: ANKRD11 (exon1), RPL13, and PGN genes. ANKRD11 deletions are frequently described in association with KBG syndrome, the duplications being less frequent (one case described before). The exome sequencing was negative for pathogenic variants or of uncertain significance in genes possibly associated with this phenotype. The patient presented subtle signs of KBG syndrome. It is known that the phenotype of KBG syndrome has a wide clinical spectrum, this syndrome being often underdiagnosed due to overlapping features with other conditions, also characterized by multiple congenital anomalies and intellectual disability. The particularity of this case is represented by the very low bone mineral density in a patient with 16q24.3 duplication. ANKRD11 haploinsufficiency is known to be associated with skeletal involvement, such as short stature, or delayed bone age. An effect on bone density has been observed only in experimental studies on mice with induced missense mutations in the ANKRD11 gene. This CNV also involved the duplication of the very conserved RPL13 gene, which could have a role for the skeletal phenotype of this patient, knowing the high level of gene expression in bone tissue and also the association with spondyloepimetaphyseal dysplasia Isidor Toutain type, in case of splicing mutations.

Rare complications of neurofibromatosis 1 diagnosed incidentally in two children.

Neurofibromatosis 1 (NF1) is an autosomal-dominant disorder with various clinical expressivity and complications. Arterial hypertension may be present in patients with NF1 and is secondary to vasculopathy or pheochromocytoma. We herein describe two children (17 and 4 years old) diagnosed late with NF1 after severe arterial hypertension had been discovered due to pheochromocytoma and middle aortic syndrome. Routine measurement of arterial pressure is mandatory in children with NF1, in order to diagnose the complications of this disease.

Ultrasonographic evaluation of the median nerve at the level of the carpal tunnel outlet and mid forearm in patients with type II Mucopolysaccharidosis.

AIMS: The ultrasonographic (US) evaluation of the median nerve at the level of the carpal tunnel outlet (CTO) and mid forearm in pediatric patients with mucopolysaccharidosis type II (MPS II) and comparison with healthy subjects. MATERIAL AND METHOD: Fifteen children with MPS II and 44 healthy children were included in the study and they were divided into three age groups. The cross-sectional area, the appearance of the nerve, and the ratio of the cross-sectional areas were evaluated by US. RESULTS: At the level of the CTO the mean area of the nerve was increased in all MPS II groups compared with the correspondent healthy age groups and the differences were statistically significant (p<0.01). At the level of the mid forearm the differences were statistically significant only for the first age group. Other US findings at the level of the CTO in the MPS II groups were represented by hypoechogenicity (86.67 % on the right and 93.33% on the left), thickened fascicles (80% bilaterally), irregular contour (53.33% bilaterally) and the presence of the Doppler signal including the nerve (26.67 % on the right and 33.33 % on the left). The CTO/mid forearm cross-sectional area ratio was higher in all MPS II age groups and the differences were statistically significant (p<0.001). CONCLUSION: In patients with MPS II there are significant US changes in the size and aspect of the median nerve.

Bowel elastography - a pilot study for developing an elastographic scoring system to evaluate disease activity in pediatric Crohn's disease.

UNLABELLED: The diagnosis and monitoring of Crohn's disease (CD) represents a diagnosis challenge in which imaging plays an important role. AIM: In the present paper we aim to demonstrate the role of sonoelastography (SE), performed in addition to hydrosonography (HS), in the evaluation of CD in children and to propose a scoring system for the appreciation of disease activity. MATERIAL AND METHOD: All the patients included into the study were diagnosed with CD and had underwent HS and SE as part of the imaging evaluation. In selected cases magnetic resonance enterography (MRE) was also performed. SE aspects were classified into three types, each corresponding to a specific bowel wall pattern: normal or remission (type A), inflammation (type B) and fibrosis (type C); this classification represents the basis of the scoring system. For the purpose of statistical analysis each evaluated bowel segment became an individual case. RESULTS: Forty eight bowel segments were evaluated by SE: 21 type A, 20 type B and 7 type C. Statistically significant correlations were found between the intestinal wall HS changes, presence of complications, activity markers and the SE score. The HS assessment of the periintestinal area correlated only partially with SE score, while certain SE scores also proved to be predictors for the presence of complications or for increased values of the disease activity markers. CONCLUSIONS: SE, along with HS, represents a reliable investigation in the correct diagnosis and monitoring of pediatric patients with CD and the SE scoring system may be introduced as a method for the assessment of disease activity.

Ovarian and uterine ultrasonography in pediatric patients. Pictorial essay.

Ultrasonography represents the method of choice in the investigation of the female pediatric pelvis. While the investigation itself poses no real challenges, an accurate interpretation of the images must take into consideration the specific features of the ovaries and uterus at certain ages. The present essay aims to demonstrate the normal appearance of the female pelvis and the changes that occur during the various stages of development as well as the some of the most common pathological conditions.

Large spectrum of complete urinary collecting system duplication exemplified by cases. Pictorial essay.

Urinary collecting system duplication is a congenital anomaly and can associate various types of urinary tract pathologies. Authors will illustrate by cases some of associated anomalies such as ureterocele, extravesical ectopic ureter, vesicoureteral reflux or reflux nephropathy; one case presented an association between posterior urethral valve and bilateral collecting system duplication.

Clinical, imaging and cystometric findings of voiding dysfunction in children.

UNLABELLED: The AIM of the study was to validate some of the imaging criteria for voiding dysfunction in children. MATERIAL AND METHODS: The study included a number of 55 children with voiding dysfunction symptoms. They were investigated clinically as well as through imaging techniques: renourinary ultrasound, voiding cystourethrography and cystometry. RESULTS: The most common symptoms were urgency (87.3%), increased frequency (81.8%), and daytime urinary incontinence (76.3%). Ultrasound scans detected a reduced bladder capacity in 65.5% patients. The voiding cystourethrography detected bladder trabeculations (58.2%) and spinning top urethra (63.6%). Cystometric recordings indicated overactive bladder in 70.9% patients. Reduced bladder capacity detected by ultrasound associated with trabeculated bladder and spinning top urethra detected by voiding cystourethrography in a patient with specific symptoms may suggest an overactive bladder. In CONCLUSION, voiding dysfunction in child can be diagnosed by minimal or non-invasive methods.

The role of ultrasonography for diagnosis the renal masses in children. Pictorial essay.

In children abdominal masses usually arises from the kidney and urinary tract. The reasons for patient's presentation may be abdominal pain, palpable abdominal mass (usually discovered during the physical exam) and hematuria. Ultrasonography should be the first imaging investigation performed in children with an abdominal mass. It can be performed safely regardless of the clinical status of the patient, it is noninvasive and painless, requires no radiological contrast media and it is a relatively inexpensive. Ultrasonography is usually able to give an accurate localization of the lesion to a specific area or organ of the abdomen and provides good differentiation of solid from fluid or blood-filled masses. The purpose of this pictorial essay is to demonstrate the ultrasonographic features of the most frequently encountered reno-urinary masses in children.

The role of ultrasonography in the evaluation of maxillary sinusitis in pediatrics.

UNLABELLED: Sinusitis in children may sometimes present non-specific signs and symptoms. The imaging techniques used for its diagnosis are computed tomography and magnetic resonance imaging, the standard radiography being used less and less. Ultrasonography is seldom mentioned in literature as a diagnosis method of sinusitis. OBJECTIVE: The purpose of this study is to evaluate the value of ultrasonography compared with the standard X-ray in the diagnosis of maxillary sinusitis in children. METHOD: The study was prospectively conducted. The study group included 76 patients who had an ultrasound of the maxillary sinuses. The including criteria were represented by uncontrolled or partially controlled asthma, symptomatology suggesting rhinosinusitis and age over 4. Patients with radiological anomalies of the maxillary sinuses were excluded from the study as well as the patients who were not examined through X-ray and the ultrasonography on the same day. The ultrasound was performed with a pediatric convex transducer with the patient in a sitting position. The ultrasonographic exam evaluated the presence of fluid collection and mucosal thickening within the maxillary sinuses. Signs evaluated by X-ray exam were: total opacity of the maxillary sinus, air-fluid level and mucosal thickening. The Wilcoxon matched-pairs tests was used in order correlate the results obtained through ultrasonography and radiograph. It was considered statistic significant p<0.05. Using the ROC curve the sensitivity and the specificity of the ultrasound compared with the standard radiograph were determined. RESULTS: Based on the excluding criteria a number of 67 patients (35 male) were selected from the study group. The patient's mean age+/-standard deviation was 9 years 2 months+/-3 years 9 months. 134 maxillary sinuses were analyzed ultrasonographically and radiologically. There was a diagnosis agreement between the two techniques in 112 out of 134 sinuses (83.5%). Compared to the standard X-ray, ultrasonography had a 94.9 % sensitivity and a 98.4 % specificity. The error of the ultrasound exam compared to the standard X-ray evaluated in a divided interpretation was low for the normal aspect (1.58%) and for the fluid collection (5.12%), but the error for the thickening of the mucosa was high, over 50% (59.37%). IN CONCLUSION: Ultrasonography may come to represent, on a larger scale, an accessible imaging alternative to the more invasive investigations used in the present in evaluating fluid collections in the maxillary sinus in pediatrics.