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Kurt F, Kendirli T, Gunduz RC, Kesici S, Akca H, Sahin S, Kalkan G, Derbent M, Tuygun N, Odek C, Gultekin-Keser A, Oguz S, Polat E, Derinoz O, Tekin D, Teksam O, 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.

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 ± 13.3 months; range, 20 days to 4 years). The mean time for spontaneous resolution was 2.8 ± 2.4 months (range, 1 week to 8 months) 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 1 year (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 10 months. Children with BND should be conservatively managed to avoid the risk of developing breast deformities before adolescence.

Among bleeding disorders, hemophilia A, hemophilia B and von Willebrand diseases are the most commonly occurring, whereas deficiencies of other coagulation factors are rare worldwide. Unlike hemophilias, which are X-chromosome linked disorders, the inheritance pattern of the rare coagulation factor deficiencies is generally autosomal recessive. In literature, association of these factor deficiencies and congenital abnormalities are especially rare. In this study, we present our cases having both rare factor deficiencies and congenital abnormalities, including Cenani-Lenz syndrome and Duane retraction syndrome.

Two Patients with X Chromosome Duplication: dupXp and dupXqStructural abnormalities of the X chromosome may lead to different phenotypes, depending on the chromosome region affected. We report phenotypic findings of two patients who had X chromosome duplications. One had a menstrual irregularity, a low hairline, cubitus valgus and suffered from dyslexia. The other had multiple congenital anomalies, severe mental-motor retardation and intractable epilepsy. The karyotypes were 46,X,dup(X) (p11.3p21) and 46,X,dup(X)(q13q25) respectively.

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.

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.

We describe a patient whose features represent a new entity within the oculo-auriculo-vertebral spectrum. The boy had right microtia, atresia of the external auditory canal, growth retardation, a complex heart defect, and extra-lobar pulmonary sequestration. The cardiac anomalies were persistent left superior vena cava, aortic stenosis, bicuspid aortic valves and subaortic membrane. Spinal films revealed complete fusion of the C2-C3 and C5-C6 vertebrae, and scoliosis of the lumbar spine. The patient's mental development was normal, and there were no abnormalities on ophthalmological examination. This report, reviews features of similar published cases, and argues why this may represent a 'new' entity within the oculo-auriculo-vertebral spectrum. The cardinal features are microtia, atresia of the external auditory canal, complex cardiac defects, growth retardation, normal mental and motor development in most cases and vertebral anomalies. All six of the patients reviewed were male raising the possibility of X-linked inheritance.

Objective: A 27-year-old woman was referred to our laboratory for genetic counseling at 26 weeks of gestation due to abnormal ultrasound findings including intrauterine growth retardation, Dandy-Walker malformation and lower extremity anomalies. Methods: Chromosome analysis was performed on fetal blood sample obtained by cardiocentesis. Result: We observed an abnormal karyotype with a structural abnormality of the long arm of chromosome 7. Both parents’ chromosomes were normal; thus, the fetal karyotype designation was 46,XX, del(7)(pter→q11::q31→qter) de novo. Skin biopsy sample was taken to confirm the karyotype after therapeutic abortion was performed. The result was identical. Postmortem examination and autopsy showed facial dysmorphism, malformations of the lower extremities and central nervous system anomalies. Conclusion: 7q interstitial deletions cause a wide spectrum of congenital abnormalities and syndromes linked to the deleted segments. Our case had a rather wide chromosome region deleted and it is important, because prenatal diagnosis was performed. Thus, the family had the chance to evaluate the situation and decided to terminate the pregnancy after genetic counseling.

Myelodysplasia refers to abnormal morphology of the bone marrow and/or peripheral blood. This condition is frequently due to myelodysplastic syndrome; however, myelodysplasia is caused by a variety of factors and is not always a sign of pre-malignant disease. We observed myelodysplastic changes in peripheral blood smears and bone marrow specimens from a patient who had chromosomal microdeletion 22q11.2 (del22q11.2). We then investigated such changes in several other patients who were newly diagnosed with del22q11.2 (n = 5 total, including the index case) and compared the findings to those in four sets of controls without this chromosomal abnormality. Specifically, the controls were children with conotruncal heart defects (n = 3); otherwise healthy children with bacterial (n = 4) or viral infection (n = 4); and healthy children (n = 4). The myelodysplasia scores in the myeloid cells and eosinophils of the children with del22q11 were higher than those in all four of the control groups. Myelodysplastic changes in the peripheral blood of children with del22q11.2 have not been reported previously. We believe that certain gene(s) in the deleted region may be responsible for the myelodysplastic changes that we observed in our patients with this chromosomal abnormality.

Neurofibromatosis 1 is an autosomal dominant disorder. Noonan's syndrome is known to be associated with neurofibromatoses. Patients with neurofibromatosis are predisposed to developing malignant tumors. The relationship between the genetic changes in the neurofibromin gene and mechanisms associated with tumor development in neurofibromatosis has been investigated. A nonsense mutation C2446T→R816X of the neurofibromin gene has been detected in some patients with the neurofibromatosis 1—Noonan's syndrome phenotype. We describe a case of an infant with the overlapping features of neurofibromatosis 1 and Noonan's syndrome who presented with rhabdomyosarcoma of the urinary bladder. The genetic analysis of our patient revealed neither mutation in the neurofibromatosis 1—guanosine triphosphatase-activating protein-related domain nor the R816X nonsense mutation. The phenotypic and genotypic features of neurofibromatosis, Noonan's syndrome, and cases with the overlapping features of both syndromes have been reviewed. The presentation of our case underlines the importance of careful examination for the clinical features of neurofibromatosis and phenotypic traits of associated diseases, especially in patients with malignant tumors. ( J Child Neurol 2003; 18: 68—72).

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.

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.

Jeune syndrome is a rare autosomal recessive disease characterized by narrow thoracic cage and short-limbed dwarfism. Seventy percent of affected individuals die in early childhood from pulmonary hypoplasia and respiratory distress due to the small size of the thorax. Growth retardation and chronic renal insufficiency due to nephronophthisis may occur in patients who survive the respiratory failure. We report a family that exhibited clinically heterogeneous features of Jeune syndrome. The 6-year-old male proband presented with skeletal deformities and chronic renal failure. A kidney biopsy revealed that nephronophthisis was the cause of the patient's kidney failure, and we diagnosed Jeune syndrome. A retrospective diagnosis of Jeune syndrome was also established for the proband's older sister, who had died of renal failure at 8 years of age. The oldest female child in the family also had thoracic deformity, and the father and paternal uncle were both of short stature and exhibited brachydactyly. Their renal function and blood pressure were normal. The findings in this family are important in that they demonstrate the clinical heterogeneity of Jeune syndrome and underline the association of renal disease with this syndrome.

This report describes the case of a male infant with neonatal Marfan syndrome who also exhibited popliteal pterygia. The patient's father had classic Marfan syndrome. The differential diagnosis in the neonatal case included congenital contractural arachnodactyly (Beals syndrome) and various forms of popliteal pterygium syndrome. We note the diagnostic features of the case, discuss the novel finding of pterygia in association with neonatal Marfan syndrome, and highlight the possible role of collagen defects in the pathogenesis of limb pterygia.

We report on a 7-month-old boy with Micro syndrome who was referred for assessment of mental-motor retardation and reduced vision with cataract. The characteristics of Micro syndrome are mental retardation, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism. The differential diagnosis includes cerebro-oculo-facio-skeletal syndrome (COFS); a syndrome involving cataract, arthrogryposis, microcephaly, and kyphoscoliosis (CAMAK); a syndrome with cataract, microcephaly, failure to thrive, and kyphoscoliosis (CAMFAK); Martsolf syndrome; Neu-Laxova syndrome; Lenz microphthalmia syndrome; and Smith-Lemli-Opitz syndrome. Till date, no renal malformations have been reported in Micro syndrome. Our patient had fusion of the lower poles of the kidneys and his left kidney was ectopic. Ocular findings are the most reliable neonatal diagnostic signs of Micro syndrome. Minor anomalies in Micro syndrome may be subtle and therefore not of significant diagnostic value. Micro syndrome is an autosomal recessive trait. Till date, most reported cases have been in individuals of Muslim origin. In countries with high rates of consanguineous marriage, such as Turkey, it is important that physicians be able to recognize this syndrome. Micro syndrome should be considered in any infant with congenital cataract.

Cerebral infarcts are rather rare in children and can be caused by a number of diverse conditions. We report a case of cerebral infarct associated with a recent varicella infection. A 5-year old girl presented with an acute central facial palsy 1 month after a chickenpox infection. The infarction was revealed by magnetic resonance imaging and laboratory studies ruled out all known causes of stroke. Cerebral angiogram demonstrated segmental narrowing and irregularity of the wall of the right internal carotid artery, compatible with focal vasculitis. With the presumed diagnosis of varicella-associated focal angiitis, the patient was treated with high-dose methylprednisolone, acyclovir and aspirin. Magnetic resonance angiogram performed 6 weeks after the stroke demonstrated the resolution of the vasculitis. Varicella infection should be considered one of the possible causes of acute ischaemic strokes in children.

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.

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. © 2010 Wiley-Liss, Inc.

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.

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.

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 raphe, 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.

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.

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder, affecting ∼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.

Myelodysplasia refers to abnormal morphology of the bone marrow and/or peripheral blood. This condition is frequently due to myelodysplastic syndrome; however, myelodysplasia is caused by a variety of factors and is not always a sign of pre-malignant disease. We observed myelodysplastic changes in peripheral blood smears and bone marrow specimens from a patient who had chromosomal microdeletion 22q11.2 (del22q11.2). We then investigated such changes in several other patients who were newly diagnosed with del22q11.2 (n = 5 total, including the index case) and compared the findings to those in four sets of controls without this chromosomal abnormality. Specifically, the controls were children with conotruncal heart defects (n = 3); otherwise healthy children with bacterial (n = 4) or viral infection (n = 4); and healthy children (n = 4). The myelodysplasia scores in the myeloid cells and eosinophils of the children with del22q11 were higher than those in all four of the control groups. Myelodysplastic changes in the peripheral blood of children with del22q11.2 have not been reported previously. We believe that certain gene(s) in the deleted region may be responsible for the myelodysplastic changes that we observed in our patients with this chromosomal abnormality.

We report on a 7-month-old boy with Micro syndrome who was referred for assessment of mental-motor retardation and reduced vision with cataract. The characteristics of Micro syndrome are mental retardation, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism. The differential diagnosis includes cerebro-oculo-facio-skeletal syndrome (COFS); a syndrome involving cataract, arthrogryposis, microcephaly, and kyphoscoliosis (CAMAK); a syndrome with cataract, microcephaly, failure to thrive, and kyphoscoliosis (CAMFAK); Martsolf syndrome; Neu-Laxova syndrome; Lenz microphthalmia syndrome; and Smith-Lemli-Opitz syndrome. Till date, no renal malformations have been reported in Micro syndrome. Our patient had fusion of the lower poles of the kidneys and his left kidney was ectopic. Ocular findings are the most reliable neonatal diagnostic signs of Micro syndrome. Minör anomalies in Micro syndrome may be subtle and therefore not of significant diagnostic value. Micro syndrome is an autosomal recessive trait. Till date, most reported cases have been in individuals of Muslim origin. In countries with high rates of consanguineous marriage, such as Turkey, it is important that physicians be able to recognize this syndrome. Micro syndrome should be considered in any infant with congenital cataract.

Background: Nephropathy is a well-known complication of congenital heart disease (CHD), and the risk of developing renal impairment is particularly high in patients with cyanotic CHD. Most investigations of renal impairment in CHD have involved patients 20 years and older. This study investigated renal tubule function in pediatric patients with CHD, and compared findings in cyanotic and acyanotic groups. Methods: Twenty children with acyanotic CHD, 23 children with cyanotic CHD, and 13 healthy children were enrolled. Blood and early morning urine samples were collected from each subject to measure urinary concentrations of sodium, microalbumin, creatinine, β2-microglobulin, and N-acetyl-β-D-glucosaminidase (NAG). Results: The age and sex distributions in the three groups were similar. Median fractional excretion of sodium (FeNa) and urinary NAG/creatinine were significantly higher in the cyanotic group than in the control group (p = 0.022 and p = 0.002, respectively). There were no statistically significant differences among the groups with respect to urinary β2-microglobulin/creatinine, urinary microalbumin/creatinine or glomerular filtration rate. Conclusion: Tubular injury can be detected before glomerular injury occurs even within the first decade of life in patients with cyanotic CHD.

A nonlethal form of multiple pterygium syndrome (MPS) was diagnosed prenatally at 16 weeks of gestation with associated Klinefelter syndrome in the same fetus. The ultrasound findings were cystic hygroma, hypertelorism, micrognathia, low-set ears, flexion contractures of upper and lower extremities and rocker-bottom foot. Genetic amniocentesis revealed a 47,XXY karyotype. After genetic counseling, the parents decided to have a therapeutic abortion. We presented this case for the purpose of further describing the early ultrasound findings and clinical features of multiple pterygium syndromes. Also, what makes our patient unique is the coincidental presence of Klinefelter syndrome with MPS. To our knowledge, this is the first case in the literature in which a 47,XXY karyotype has been found in a fetus with multiple pterygium syndrome. The importance of delineating the exact subtype of MPS and making a precise differential diagnosis becomes critical during the process of evaluation of patients with MPS.

We report a 6-year-old patient with hemophilia A, who also exhibited clinical features typical of 22q11.2 deletion syndrome (22qDS). The specific traits were mild mental retardation, speech delay, hypernasal speech, deficits in voice quality and articulation, narrow palpebral fissures, broad and depressed nasal root, high-arched palate, microstomia, and overfolded ears. The patient had no associated congenital cardiac or palatal malformations. It can be particularly difficult to identify this syndrome in newborns and infants without congenital heart defects. This case underlines that microdeletion of chromosome 22q11.2 should be considered in any patient who exhibits typical clinical features of 22qDS, regardless of whether they have another single-gene disorder.

We report a case of idiopathic pulmonary hemosiderosis (IPH) in a three-year-old male patient who presented with severe iron deficiency anemia. The child had been diagnosed with iron deficiency anemia nine months earlier and had received multiple blood transfusions, but the cause of his anemia had not been established. The diagnosis of IPH was made after a biopsy of the left lung showed large numbers of hemosiderin-filled macrophages in the alveoli. He did not respond to standard dose corticosteroid (CS) treatment (2 mg/kg/d). However, high-dose short-term CS treatment was successful in two episodes of acute respiratory hemorrhage in this patient. We conclude that IPH should always be considered when investigating the cause of iron deficiency anemia. A more rapid diagnosis in this case could have prevented unnecessary investigations and blood transfusions. We also suggest that high-dose short-term CS treatment should be kept in mind, especially in patients who do not respond to a standard dose.

This report describes a patient who had some phenotypic features of Down syndrome (DS) as well as severe conotruncal cardiac anomalies, including pulmonary atresia with ventricular septal defect (tetralogy of Fallot with pulmonary atresia), confluent pulmonary arteries, a large left-sided ductus arteriosus, left aortic arch, aberrant right subclavian artery, and secundum atrial septal defect. Cytogenetic and fluorescence in situ hybridization (FISH) analysis was carried out on peripheral blood lymphocytes and skin fibroblasts using probes specific for the chromosomal loci 21q22.13 to 21q22.2 and locus 22q11.2. This revealed 47,XX+21/46,XX mosaicism at a rate of 15:85 and the micro-deletion 22q11.2 (del22q11.2). Some patients'congenital cardiac anomalies are atypical for the type of mosaicism or aneuploidy. The case suggests that association of del22q11.2 should be considered in patients with chromosomal mosaicism or aneuploidy who also have particular conotruncal cardiac defects.

Frontonasal dysplasia (FND) is a congenital malformation characterized by hypertelorism, broad nasion with a midline cleft in the bony dorsum, midline defect of the frontal bone, absence of the nasal tip, and deformities in the nasal alar region. The clinician should be aware of the mild forms of FND. We presented absence of crista galli in a mild case of FND. Computed tomography scanning should assess the facial bones, nose, and paranasal structures. If a surgical correction is planned, this complete work-up prevents unexpected complications and complements the evaluation of paranasal deformities.

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.

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.

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. © 2010 The American Society of Human Genetics.