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KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of −1 SDs to −2 SDs were noted in about half of the patients; only two patients presented with short stature below −3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.

The Neurofascins (NFASCs) are a family of proteins encoded by alternative transcripts of NFASC that cooperate in the assembly of the node of Ranvier in myelinated nerves. Differential expression of NFASC in neurons and glia presents a remarkable example of cell-type specific expression of protein isoforms with a common overall function. In mice there are three NFASC isoforms: Nfasc186 and Nfasc140, located in the axonal membrane at the node of Ranvier, and Nfasc155, a glial component of the paranodal axoglial junction. Nfasc186 and Nfasc155 are the major isoforms at mature nodes and paranodes, respectively. Conditional deletion of the glial isoform Nfasc155 in mice causes severe motor coordination defects and death at 16–17 days after birth. We describe a proband with severe congenital hypotonia, contractures of fingers and toes, and no reaction to touch or pain. Whole exome sequencing revealed a homozygous NFASC variant chr1:204953187-C>T (rs755160624). The variant creates a premature stop codon in 3 out of four NFASC human transcripts and is predicted to specifically eliminate Nfasc155 leaving neuronal Neurofascin intact. The selective absence of Nfasc155 and disruption of the paranodal junction was confirmed by an immunofluorescent study of skin biopsies from the patient versus control. We propose that the disease in our proband is the first reported example of genetic deficiency of glial Neurofascin isoforms in humans and that the severity of the condition reflects the importance of the Nfasc155 in forming paranodal axoglial junctions and in determining the structure and function of the node of Ranvier.

KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of −1 SDs to −2 SDs were noted in about half of the patients, only two patients presented with short stature below −3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.

Evaluation of diagnostic and treatment procedures in children with cystic fibrosis (CF) operated on because of meconium ileus (MI).The authors retrospectively reviewed the documentation of 10 CF newborn patients operated on in the years 2000-2014 because of MI. In prenatal ultrasound (US) examinations, suspicion of bowel abnormalities was raised in 2 cases, even though all the 10 mothers had a minimum of 3 US examinations during pregnancy. The mean gestational age of the newborns was 39.2 weeks - 36-41 weeks), their mean birth weight 3472g (2560-4550 g). Family history of CF was positive in two patients. Genetic testing was performed in all the children operated on.In all the children operated on, mutations in both alleles of the CFTR gene were found. Five patients were F508del homozygotic, 4 were heterozygotic for this mutation, one had another mutation. Sweat tests were positive in all the children. Abdominal distention was observed in 9 patients, vomiting and retention of gastric contents in 5. In 8 children meconium was not passed at all. 2 children passed a small amount of viscid meconium. Before the operation, rectal saline washouts were done in 5 newborns. Five patients were operated on during the first day of life, four on the second day and one on the third day of life. Intra-operatively a simple form of MI was diagnosed in 8 cases, a complicated form in 2 cases. In patients with the simple form of MI, a Bishop-Koop stoma was created after the evacuation of meconium. Two of these children needed a resection of some centimetres of dilated terminal ileum with doubtful viability. In newborns with the complicated form of MI, the treatment was individualized, always with stoma formation. The time of postoperative meconium evacuation through enterostomy ranged from 6 to 15 days. Enteral feeding was started on average on the 9th day postoperatively. The mean hospital stay was 22.9 days. In 8 children the stoma was taken out at the mean age of 19.4 months, in one patient the stoma closed spontaneously. No disturbances in electrolyte balance or excessive fluid loss, nor any body weight deficits connected with the stoma were observed. There were no complications during stoma closure. All the patients are alive. The time of observation ranges from 7 to 146 months (average 95 months). All the patients currently present respiratory symptoms, have pancreatic insufficiency and need pancreatic enzyme supplementation. Seven do not, however, have body weight and height deficits. All the children with weight and height deficits have abnormal liver function tests. During observation two patients had MI equivalent symptoms, which was resolved by conservative treatment.1. In every case of intra-operative diagnosis of MI, it is necessary to perform genetic testing and sweat tests to confirm or exclude CF. 2. Mechanical intra-operative decompression of the bowel from inspissated meconium with a temporary stoma, which makes the continuation of bowel decompression possible in the postoperative period, is an effective treatment in children with MI. 3. The Bishop-Koop stoma, permitting the passage through the whole gastrointestinal tract, is a safe option. In our material, no complications of this stoma, such as stoma care problems or dyselectrolithemia were observed. 4. The decision of stoma closure in children with MI and CF should be delayed until the moment of introducing a broadened diet and should be undertaken together with a pediatrician who is a specialist in CF therapy. .

Twenty-four children with giant congenital melanocytic nevi underwent brain MRI at 1.5 T scanner. Melanin deposits in the brain were found in seven children (29.2%) located in temporal lobes, thalamus, cerebellum, and pons. One patient showed leptomeningeal involvement. Six patients were asymptomatic, and one had epilepsy. As opposed to previous reports, localization of skin nevi on anterior part of trunk was correlated to central nervous system involvement. In all patients with brain involvement skin nevi showed picture of compound nevus with neurofibromatic component.

Progress in perinatology and neonatal intensive care led to surgical treatment of premature infants born with low (1500 g) and extremely low (1000 g) birth weight.Evaluation of surgical treatment in the group of neonates with very low birth weight (1500 g) and extremely low birth weight (1000 g).In the years 2000-2009 in the Department of Paediatric Surgery in the Institute of Mother and Child, 617 neonates underwent surgical treatment, 101 of them (16%) were born with very low or extremely low birth weight. In the analyzed group the birth weight ranged from 450 g to 1500 g (mean 952 g), gestational age ranged from 23 weeks to 32 weeks (mean 27 weeks). Fifty four patients (53%) were operated with the weight1000 g. Indications for surgery were of two categories: pathologies related to prematurity and congenital defects. The extend of surgical intervention is presented. Additional pathologies influencing prognosis such as respiratory distress syndrome, haemodynamic ductus arteriosus, intraventricular haemorrhagia, multiple congenital defects and genetic disorders were also taken into consideration. Mortality in the entire group of patients was evaluated in relation to the birth weight, gestational age, reasons for surgical treatment and additional risk factors.Pathologies related to prematurity were indications for surgical treatment in 70 patients: perforation of the bowel in the course of necrotizing enterocolitis - NEC (28 patients), spontaneous intestinal perforation - SIP (32), gastric perforation - GP (4), meconium obstruction - MO (3) posthemorrhagic hydrocephalus - PH (3). In the remaining 31 neonates the following congenital defects were operated: inguinal hernia (10 patients), oesophageal atresia (8), anal atresia (2), torsion of the bowel (2), bowel atresia (3), hernia of the umbilical cord (3), ruptured omphalocele (1), myelomeningocele (2). In the entire group of 101 premature infants, 99 patients (98%) had respiratory distress syndrome, 56 (56%) required the closure of ductus arteriosus , in 55 patients (55%) intraventricular haemorrhage from II to IV degree was confirmed. In total thirty patients died. Twenty one of them were ELBW neonates. None of the patients died during the operation or within the first postoperative day. Mortality rate in the group with the weight1000 g was 38%, in the group with the weight 1000 g-1500 g it was 19%. Highest mortality was observed in the patients with oesophageal atresia (62%) In this group the biggest number of additional anomalies or other genetic disorders was found. Twenty infants died (31%) in the group of 64 neonates with perforations. Mortality rate in the groups with the weight1000 g and 1000 g-1500 g it was 34% and 26% respectively. Our results confirmed the significant difference between mortality in NEC - 65% and in SIP - 19.5% . The remaining 5 deaths were related both to extreme multiorgan prematurity and severe congenital defects.The most frequent indications for surgery in premature neonates (VLBW and ELBW) are acquired pathologies which are related to premature multiorgan insufficiency: perforations in the course of ischaemic or inflamatory changes in the bowel (NEC, SIP), intestinal obstruction related to functional insufficiency of alimentary tract (MO) and posthaemorrhagic hydrocephalus. Congenital anomalies constitute 30% of indications for surgical treatment in this group of patients. Neonates born with low or extremely low birth weight are in the group of patients with the highest intraoperative risk. There is herefore a need to create well equipped, interdisciplinary centres employing paediatric surgeons, anaesthesiologists and neonatologists experienced in treatment of extremely premature neonates.

Myelomeningocoele is a serious congenital deformity requiring multidisciplinary medical care, and parent' s aware cooperation. The accessibility and popularity of foetal ultrasonography enables early prenatal diagnosis which makes possible optimal management during pregnancy and treatment after birth.Evaluation of the treatment of newborns with myelomeningocoele in the last 20 years in relation to the changes in diagnostics and operative procedures.The evaluation was performed in 114 newborns, operated on because of myelomeningocoele between 1986-1992 (group I) and 1999-2005 (group II). Prenatal diagnosis, the term and kind of labour, anatomical description of deformity, the level of spinal cord damage were analyzed. Evaluation also included: the term and kind of operation, the presence of active hydrocephalus and its association with the anatomical picture of deformity, the strategy of shunt implantation and the number of deaths during the first hospitalization. Orthopaedic and urological problems were not evaluated.During twenty years, reduction in the number of patients with myelomeningocoele was not observed, despite the introduction of the programme of women' s folic acid prophylaxis. In two analyzed periods there were 8 new cases treated each year. The number of prenatal diagnoses increased: in group I prenatal diagnosis was made only in 8 cases (14%), in group II in 25 cases (44%), but in most cases diagnosis was established late (in the last 3 months of pregnancy). Analysis of different anatomical forms of the deformity showed, that the number of thoracic myelomeningocoeles decreased from 32 cases in group I to 18 cases in group II. In both groups operation was performed during 24 hours following admission of the newborn to the Institute. The surgical technique has not change: large skin defects were closed with the use of rhomboidal muscle and skin flap (Limberg' s plasty). The number of complications in wound healing decreased from 26.4% to 7%. Active hydrocephalus was confirmed in 49 of 57 patients in group I (85%) and in 46 of 57 patients in group II (80%). Patients without active hydrocephalus (group I - 8 children, group II - 11 children) presented lumbo-sacral or sacral localization of defect. In the years 1999-2005 (group II), contemporary with the operation of myelomeningocoele, Rickham reservoir was implanted in 11 newborns with massive hydrocephalus. The shunt was added after the confirmation of active hydrocephalus and after a negative result of cerebrospinal fluid culture. Decrease of deaths during the first hospitalization was observed (8 in group I, 2 in group II). The principal cause of death in both groups was inborn infection.1. On the basis of own investigations the authors did not find positive results of introducing of women' s folic acid prophylaxis programme in Poland in the decrease of number of newborns, treated surgically on spina bifida in the Institute of Mother and Child. In the last years more often sacral and lumbo-sacral type of defects and, in consequence, more patients without active hydrocephalus are observed, which may be the result of parent' s decision about terminating of pregnancy in cases of high (thoracic) deformity. 2. In the years 1999-2005 the increasing number of prenatal ultrasonography is observed. However, the prenatal diagnosis of myelomeningocele in most cases is established late (in the third trimester). 3. Significant fall in the number of local and general complications of treatment is responsible for the decrease in mortality of the newborns with myelomeningoloele. The method of closing large skin defects using cutaneo-muscular rhomboidal flap, introduced in 1986, showed to be very effective in the prophylaxis of complications of wound healing. 4. Congenital intrauterine infection was the main cause of death of neonates with this deformity, what points to the necessity of regular bacteriological and serological diagnostics during pregnancy and proper perinatal treatment.

Inguinal hernia in preterm infants is a difficult therapeutic problem because of the risk of anaesthesia and the immaturity of the baby. Despite of high risk of perioperative complications surgical repair of the hernia should be considered before discharge.evaluation of the perioperative problems in the preterm infants with inguinal hernia.evaluation was performed in 21 preterm infants (gestational age 23-36 weeks, birth weight 450-1370 g) operated because of inguinal hernia between 2002-2007. Various problems related to prematurity were confirmed in all patients. Incarcerated hernia were operated on in 5 patients, in 16 neonates hernia repair was performed as elective surgery. In two of them, few weeks after unilateral hernia repair, operation on the other side was performed because of incarceration. Nine infants were qualified for general anaesthesia, fourteen for spinal anaesthesia. Indications for surgical treatment, method of anaesthesia and early postoperative results were analysed with reference to various problems connected with prematurity such as intraventricular haemorrhage and chronic lung disease.inclusively 23 operations were performed in 21 infants (gestational age 36-47 weeks, weight 1130 -2750 g). Four of fourteen infants preliminary qualified for spinal anaesthesia turned into general anaesthesia. There were not any problems during the operations. Two patients required short ventilatory support (both with general anaesthesia because of incarcerated hernia). During a follow up examination recurrence of the hernia was not observed in any of the patients.despite of high risk of perioperative complications in preterm infants, surgical repair of the inguinal hernia should be considered before discharge. Spinal anaesthesia is a safe alternative for general anaesthesia in preterm infants especially for infants with chronic lung disease.

THE AIM of the second part of the study was an evaluation of the treatment in newborns with congenital duodenal obstruction.In the years 1992-2002 in the Department of Paediatric Surgery at the institute of Mother and Child in Warsaw, 601 newborns with congenital anomalies requiring early surgical intervention were treated. Congenital duodenal obstruction was diagnosed in 35 neonates with birth weight from 800 g to 3450 g. Thirty three patients were operated. Ten of them had associated anomalies of the cardiovascular system, gastro-intestinal and urinary tracts. Additionally, in three of them genetic disorders were suspected. Treatment of all 35 newborns was analysed in order to identify factors influencing prognosis in babies with congenital duodenal obstruction.Twenty-five patients survived (72%), ten patients died (28%). There were not any surgical complications. Two premature infants had died before operative repair, eight neonates after it (8-32 day). Six of them were premature babies with respiratory problems and in three of them genetic disorders were confirmed: Down's syndrome, Cornelia di Lange syndrome and aberration of the fourth and seventh pair of chromosomes. Additionally in six of them serious intrauterine infection was diagnosed. Mortality rate considerably decreased in the last five years, seven deaths occurred between 1992 and 1997 and only one after this time.Two groups of risk factors had influence for prognosis in neonates with congenital duodenal obstruction and they were not connected with operative procedures. Associated genetic disorder were the first group of serious risk factors having influence on prognosis, independently of surgical disease. On the other hand prematurity with severe respiratory problems and coexisting intrauterine infection were the most important prognostic factors in survival. Progress in prenatal diagnosis and neonatal intensive care had fundamental influence for improvement of results in the last 5 years.