Outcome of out-of-hospital cardiopulmonary arrest in children: A multicenter cohort study.

Kurt F, Kendirli T, Gündüz RC, Kesici S, Akça H, Sahin S, Kalkan G, Derbent M, Tuygun N, Ödek Ç, Gültekin-Keser A, Oguz S, Polat E, Derinöz O, Tekin D, Teksam Ö, Bayrakci B, Suskan E. Outcome of out-of-hospital cardiopulmonary arrest in children: A multicenter cohort study. Turk J Pediatr 2018; 60: 488-496. The aim of this study was to evaluate the demographic characteristics of children who experienced out-of-hospital cardiopulmonary arrest (CPA), and to assess the impact of the bystander cardiopulmonary resuscitation (CPR) on the survival rate of witnessed arrests and the effects of the arrest and CPR durations on the neurological outcomes. This multicenter, retrospective study included a total of 182 patients who underwent CPR for out-of-hospital CPA between January 2008 and December 2012 at six centers in Ankara, Turkey. The median [interquartile range (IQR)] age was 22 (5-54) months; 60.4% of the patients were males, and 44% were younger than one year of age. The witnessed arrest rate was 75.8% (138/182) and the rate of bystander CPR was 13.9% (13/93). In these patients the rate of the return of spontaneous circulation (ROSC) was higher (76.9%). Following resuscitation in the patients for whom the spontaneous circulation was able to be returned, the median (IQR) duration of arrest was 5 (1- 15) min, while it was 15 (5-40) min for the remaining patients (p < 0.001). The ROSC rate was 94.9% in patients who underwent CPR for less than 20 min and 22% in patients requiring CPR longer than 20 min (p < 0.001). Survival to hospital discharge was 14.3%. Of these patients, 57.7% experienced neurological disability. The short duration of an arrest and the presence of CPR are both critical for survival. We suggest that a witness to the CPA, performing early and efficient CPR, yields better results.

Bloody nipple discharge as a benign, self-limiting disorder in young children: A systematic review including two related case reports.

BACKGROUND/PURPOSE: Bloody nipple discharge (BND) is rare, distressing for parents, and presents a challenge for physicians. METHODS: We used PubMed to search for cases of BND that were diagnosed before adolescence and added data from two of our cases. RESULTS: The analyzed cohort comprised 46 patients (28 boys and 18 girls; mean [SD] age, 12.5±13.3months; range, 20days to 4years). The mean time for spontaneous resolution was 2.8±2.4months (range, 1week to 8months) after onset of BND without any intervention. The diagnosis was mammary ductal ectasia (MDE) in 15 patients, gynecomastia with MDE in two patients, hemorrhagic cysts in two patients, and gynecomastia alone in one patient. The majority (89.3%) of patients <1year old were managed conservatively, but half of them aged >1year (50.0%) underwent surgery. Surgery was performed more often in patients in whom a mass had been identified. CONCLUSIONS: Age and findings at physical examination affect selection of treatment, but not sex. We found no reported cases of malignancy. Symptoms in children who are managed conservatively resolve within 10months. Children with BND should be conservatively managed to avoid the risk of developing breast deformities before adolescence.

Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome.

Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome (MIM 600373) was first described and named by Shehib et al, in 1991 in a single patient. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. This distinctive constellation of anatomical findings should allow easy recognition but despite this only four apparently sporadic patients have been reported in the last 20 years indicating that the full phenotype is indeed very rare with perhaps milder or a typical presentations that are allelic but without sufficient phenotypic resemblance to permit clinical diagnosis. We performed exome sequencing in three patients (an isolated case and a brother and sister sib pair) with classical features of CODAS. Sanger sequencing was used to confirm results as well as for mutation discovery in a further four unrelated patients ascertained via their skeletal features. Compound heterozygous or homozygous mutations in LONP1 were found in all (8 separate mutations; 6 missense, 1 nonsense, 1 small in-frame deletion) thus establishing the genetic basis of CODAS and the pattern of inheritance (autosomal recessive). LONP1 encodes an enzyme of bacterial ancestry that participates in protein turnover within the mitochondrial matrix. The mutations cluster at the ATP-binding and proteolytic domains of the enzyme. Biallelic inheritance and clustering of mutations confirm dysfunction of LONP1 activity as the molecular basis of CODAS but the pathogenesis remains to be explored.

A collodion baby with facial dysmorphism, limb anomalies, pachygyria and genital hypoplasia: a mild form of Neu-laxova syndrome or a new entity?

Neu-Laxova syndrome is a rare, lethal, autosomal recessive disorder characterized by intrauterine growth retardation, central nervous system anomalies, skin findings, such as ichthyosis, edema, collodion baby and harlequin fetus, facial dysmorphic features, limb anomalies and genital hypoplasia. Although it is generally a lethal condition, cases of such patients who lived beyond 6 months and 10 months of age have been reported. Here, we describe an 8-year-old boy who was born with collodion membrane, facial dysmorphic features, limb anomalies, genital hypoplasia and pachygyria. He had no major health problems over the course of 8 years of follow-up, except for mild mental/motor retardation, ichthyosis, facial dysmorphic features and limb anomalies. Based on these features, we suggest that because Neu-Laxova syndrome represents a heterogeneous phenotype, our case may be a milder variant of this syndrome or a new genetic entity.

A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene.

Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations. The cause of MWS is a de novo mutation in the ZEB2 gene. This report describes a Turkish boy who was clinically diagnosed with MWS and had his diagnosis confirmed by molecular analysis of the ZEB2 gene. The investigation identified a heterozygous complex rearrangement in exon 8 of ZEB2, specifically a 48-nucleotide deletion and a 44-nucleotide insertion that caused a frameshift. MWS is a relatively newly identified disorder, and even MWS patients without Hirschsprung disease can be diagnosed easily based on clinical findings alone.

Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations.

Reports on Noonan syndrome (NS) have documented multiple types of coagulation defects and bleeding diathesis, and a wide range of clinical presentations. Early studies suggested that a large proportion of NS patients have coagulation defects, whereas more recent reports indicate low rates of coagulopathy. The aim of this study was to evaluate phenotypic characteristics, PTPN11 gene mutations, and hematological and coagulation parameters in 30 clinically diagnosed cases of NS. One of the NS patients had a history of easy bruising; however, his hematological and coagulation tests were normal. None of the other patients had clinical coagulation problems. In the NS group, values for platelet count, activity of factors XI, XII, and protein C were significantly lower than the corresponding means for the control group. However, the results of coagulation tests in the NS group were diagnostically inconclusive and only one patient had clinical signs of coagulopathy. Interestingly, two NS patients had low protein C activity. One of these children had an A1517C mutation and transient myelodysplasia. The other patient had a C1528G mutation in exon 13 that has not been reported previously. Neither of these individuals experienced a thrombotic event or any complication during approximately 3 years of follow-up. For all patients clinically diagnosed with NS, a thorough history of coagulation issues should be taken and first-line coagulation testing should be done to evaluate for bleeding diathesis. However, if these assessments reveal nothing abnormal, complications related to coagulation are unlikely and extensive testing is unnecessary.

Mutations in HPSE2 cause urofacial syndrome.

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.

Propranolol for infantile hemangiomas: a preliminary report on efficacy and safety in very low birth weight infants.

Despite the relatively recent introduction of propranolol in the treatment of infantile hemangiomas, there can be little doubt of its efficacy. With regard to safety issues, there are no prior data for very low weight infants. In this study, we used propranolol in preterm and very low weight infants. We used clinical criteria to assess the response to the therapy. We noted all side effects expected from beta-adrenergic blocking drugs, and followed the patients' weight gain during propranolol treatment. Objective, clinical evidence of hemangioma regression was seen after two months in all patients. None of the patients required treatment discontinuation due to adverse side effects. During the propranolol treatment, weight gain was normal in all patients. To the best of our knowledge, this is the first report on the use of propranolol in preterm and very low weight infants, and also the first report from Turkey on the use of propranolol in infantile hemangiomas.

Urofacial (ochoa) syndrome: can a facial gestalt represent severe voiding dysfunction?

Urofacial (Ochoa) syndrome is a rare autosomal-recessive disorder that features an unusual "inverted" facial expression, such that patients appear to be crying when they smile. This syndrome also involves serious urinary tract disorders, though the diagnosis may be missed because of variability of these problems and failure to recognize the characteristic facial grimacing. The urinary issues usually result in enuresis, urinary tract infection, and hydronephrosis, and some severely affected patients become hypertensive and progress to end-stage renal disease. Early diagnosis is very important for management of urinary problems and best prognosis in these patients. We report the first published case of urofacial syndrome in Turkey. The patient was diagnosed at 16 years of age, after having been followed with the diagnosis of recurrent urinary tract infection and vesico-ureteral reflux. Physicians should keep this syndrome in mind for any patient who presents with dysfunctional voiding, particularly in countries with high rates of consanguineous marriage.

Tetralogy of Fallot and hypertrophic cardiomyopathy in a case of cardiofaciocutaneous syndrome.

Cardiofaciocutaneous (CFC) syndrome is a rare disorder characterized by psychomotor and growth retardation, a typical facial dysmorphism, congenital heart defects, and ectodermal abnormalities. Pulmonic stenosis, atrial and ventricular septal defects, patent ductus arteriosus, and hypertrophic cardiomyopathy are cardiac findings identified in patients with this syndrome; however, tetralogy of Fallot has never been associated with CFC syndrome. CFC should be considered in patients with skin abnormalities in addition to phenotypic features and a congenital heart defect, including tetralogy of Fallot.

Functional pulmonary atresia in a patient with neonatal Marfan syndrome caused by a c.3602G>A mutation in exon 29 of the FBN1 gene.

Neonatal Marfan syndrome is a severe form of the syndrome mostly caused by de-novo mutations in the fibrillin-1 gene. We report a newborn with neonatal Marfan syndrome and functional pulmonary atresia who died from congestive heart failure on postnatal day 22 despite treatment. He had a mutation in exon 29 of the fibrillin-1 gene at position c.3602G>A. Functional pulmonary atresia may be a life-threatening cardiovascular manifestation of neonatal Marfan syndrome.

Oxidant/antioxidant status and vitamin A levels in children infected with varicella.

AIM: Varicella is a childhood disease, with its highest incidence being found in children aged 1 to 9 years. The aim of this study was to investigate the plasma oxidant and antioxidant status in Turkish children with varicella infection. METHODS: The study population consisted of 29 children infected with varicella recruited from the Department of Pediatrics at Baskent University Hospital in Ankara, Turkey. The control group consisted of 20 age-matched children from the same region who were apparently otherwise healthy. After overnight fasting, venous blood samples were obtained and transferred to heparinized tubes. Plasma malondialdehyde and vitamin A levels were measured in both groups. RESULTS: The plasma malondialdehyde levels were higher in children in the infected group than they were in children in the control group. However, there were no statistically significant differences in plasma vitamin A levels between the groups. CONCLUSION: This study suggests that oxidant stress causes significant peroxidation, and the antioxidant defence system is affected in varicella infection. Antioxidant supplementation may yield beneficial results in these patients. Further studies are needed to determine the positive effects of vitamin A supplementation in patients with varicella infections.

Congenital partial arhinia: a case report.

Congenital arhinia is an extremely rare anomaly consisting of an absence of external nasal structures and nasal passages. Fewer than 30 cases have been reported. Patients with a familial absence of the nose have been reported, but the effects of genetic and maternal factors are unknown. Midface hypoplasia may accompany arhinia. Accompanying malformations are thought to be caused by an absent or rudimentary nose. A patient with partial congenital arhinia is presented and the embryology and literature review are discussed.

PHACES syndrome with small, late-onset hemangiomas.

Although hemangiomas are the hallmark of the PHACES syndrome, they may be nonexistent at birth and may not develop until later in early infancy. We report an infant who presented initially with cardiac defect, sternal nonunion, supraumbilical raphé, and congenital hypothyroidism without any hemangioma, and who subsequently developed facial hemangiomas at 2 months of age. We noted that there is a possibility that hemangiomas may subsequently develop later in early infancy and congenital hypothyroidism may be associated with the PHACES syndrome.

Two neurofibromatosis type 1 cases associated with rhabdomyosarcoma of bladder, one with a large deletion in the NF1 gene.

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder, affecting approximately 1 in 3,500 individuals worldwide. Mutations of the NF1 tumor suppressor gene predispose individuals to a variety of benign and malignant tumors. Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma and is also a rare tumor type in NF1 patients. We report two cases of NF1 with RMS. The first is that of an infant with overlapping phenotypic features of NF1 and Noonan syndrome (NS) who presented with RMS of the bladder. The second infant likewise exhibited NF1 features and was also associated with bladder RMS. DNA samples were extracted from peripheral blood and tumor tissue samples. We performed loss of heterozygosity (LOH) analysis of the NF1 gene by using seven intragenic markers (IVS27AAAT2.1, IVS27EVI-20, IVS27AC24.8, IVS27AC28.4, M98509, IVS27AC33.1, IVS38TG53.0) and one extragenic polymorphic marker (3'NF1). A large deletion was detected in the NF1 gene in the NF1-Noonan syndrome (NF-NS) case associated with RMS.

Brachydactyly short-stature hypertension syndrome: a case with associated vascular malformations.

Brachydactyly short-stature hypertension syndrome, also known as hypertension-with-brachydactyly (HTNB) syndrome, is a rare autosomal dominant disorder that was first described by Bilginturan and colleagues in 1973. Many familial cases of HTNB have been reported, but the first sporadic case of this condition was published only recently. This article describes a case of HTNB syndrome in a 16-year-old boy. Although Doppler ultrasonography of the kidneys and renal arteries showed normal findings, magnetic resonance angiography showed an aberrant right posterior inferior cerebellar artery, early bifurcation of the left renal artery, and irregularity and stenosis of the inferior dominant branch of this artery. The patient's father was in chronic renal failure of which the primary pathology was unknown. We speculate that the described case is the second documented sporadic case of HTNB syndrome. This disorder should be included in the differential diagnosis of patients with short stature and hypertension of unknown aetiology. Such individuals should be carefully examined for brachydactyly and for cerebral-cerebellar and renal vascular malformations.