Novel Compound Heterozygous Mutations of TGM1 Gene Identified in a Turkish Collodion Baby Diagnosed with Non-Bullous Congenital Ichthyosiform Erythroderma.

Autosomal recessive congenital ichthyosis (ARCI) is a group of diseases presenting as collodion baby at birth. ARCI is categorized as Harlequin ichthyosis, lamellar ichthyosis, and non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit icthyosis (BSI) and others. We describe the case of a male newborn with NBCIE whose whole exome sequencing revealed two variants of TGM1 gene (NM_000359.3) in a compound heterozygous state: c.790C>T (p.Arg264Trp) in exon 5 and c.2060G>A (p.Arg687His) in exon 13. In the literature, the Arg264Trp variant has been reported as homozygous or compound heterozygous with other variants in patients with BSI. In contrast, the Arg687His variant has been reported only as homozygous in patients with BSI. To the best of our knowledge, this is the first case whose two compound heterozygous variants, exhibiting the NBCIE phenotype, instead of the BSI.

Using the center of pressure movement analysis in evaluating spontaneous movements in infants: a comparative study with general movements assessment.

BACKGROUND: Researchers have attempted to automate the spontaneous movement assessment and have sought quantitative and objective methods over the past decade. The purpose of the study was to present a quantitative assessment method of spontaneous movement using center-of-pressure (COP) movement analysis. METHODS: A total of 101 infants were included in the study. The infants were placed in the supine position on the force plate with the cranial-caudal orientation. In this position, the recording of video and COP movement data were made simultaneously for 3 min. Video recordings were used to observe global and detailed general movement assessment (GMA), and COP time series data were used to obtain quantitative movement parameters. RESULTS: According to the global GMA, 13 infants displayed absent fidgety movements (FMs) and 88 infants displayed normal FMs. The binary logistic regression model indicated significant association between global GMA and COP movement parameters (chi-square = 20.817, p < 0.001). The sensitivity, specificity, and overall accuracy of this model were 85% (95% CI: 55-98), 83% (95% CI: 73-90), and 83% (95% CI: 74-90), respectively. The multiple linear regression model showed a significant association between detailed GMA (motor optimality score-revised/MOS-R) and COP movement parameters (F = 10.349, p < 0.001). The MOS-R total score was predicted with a standard error of approximately 1.8 points (6%). CONCLUSIONS: The present study demonstrated the possible avenues for using COP movement analysis to objectively detect the absent FMs and MOS-R total score in clinical settings. Although the method presented in this study requires further validation, it may complement observational GMA and be clinically useful for infant screening purposes, particularly in clinical settings where access to expertise in observational GMA is not available.

An investigation of motor development and sensory processing skills in infants with a history of hyperbilirubinemia.

BACKGROUND: Hyperbilirubinemia is a clinical picture frequently occurring in the neonatal period and may negatively affect the development of infants. AIMS: To evaluate term infants with hyperbilirubinemia in terms of both motor development and sensory processing skills and to compare them with their healthy peers without hyperbilirubinemia. STUDY DESIGN: A cross-sectional study. SUBJECTS: Children born at term, aged 10-18 months, with and without a history of hyperbilirubinemia were included in the study. OUTCOME MEASURES: After demographic information was recorded, motor development was evaluated with the Peabody Motor Development Scale-2 and sensory processing skills were evaluated with the Test of Sensory Function in Infant. RESULTS: A total of 42 children (mean ± SD age of the children 13.07 ± 1.47 months, 22 with hyperbilirubinemia and 20 without hyperbilirubinemia) were included in the study. A statistically significant difference was found in the gross motor (p = 0.02), fine motor (p = 0.03), and total motor (p = 0.017) development scores of the Peabody Motor Development Scale-2 and in the adaptive motor functions (p = 0.004), visual tactile integration (p < 0.001), and total scores (p = 0.004) of The Test of Sensory Function in Infant in favor of the control group. CONCLUSIONS: The motor and sensory processing skills of children born at term with hyperbilirubinemia may be negatively affected. Infants with hyperbilirubinemia should be evaluated from the early period not only in terms of motor but also sensory processing skills and should be supported with appropriate intervention programs.

Neonatal Seizures and Future Epilepsy: Predictive Value of Perinatal Risk Factors, Electroencephalography, and Imaging.

CONTEXT: There are limited data in the literature about the relationship between neonatal seizures and subsequent epilepsy. AIMS: This study aimed to identify the predictive value of perinatal factors, etiologies, electroencephalography (EEG), and cranial ultrasonography (USG) for future epilepsy after neonatal seizures. MATERIALS AND METHODS: A total of 92 children with epilepsy who had seizures during their neonatal period were retrospectively evaluated whether the contribution of perinatal, natal, and postnatal risk factors confining clinical, laboratory, EEG, and imaging to subsequent epilepsy. Chi-square, uni, and multivariate logistic regression were applied to find out predictive factors for subsequent epilepsy. RESULTS: The rate of epilepsy was 57.6 % during 1-6 years follow-up. Birth weight, Apgar scores at first and fifth minutes, resuscitation history, abnormal neurological examination, etiology, response to the treatment, abnormal EEG, or USG findings were the most important risk factors for future epilepsy in univariate analysis (P < 0.05). Furthermore, asphyxia, fifth minute Apgar scores, response to the treatment, USG, and EEG were independent predictors (P < 0.05) for subsequent epilepsy in multivariate logistic regression. No relationship was found between subsequent epilepsy and mode of delivery, seizure onset time, and seizure types (P > 0.05). CONCLUSION: Although there are recent promising and advanced techniques in neonatal intensive care units, asphyxia is still one of the most important risk factors for not only poor neurological conditions but also for future epilepsy after neonatal seizures. Apgar scores, treatment with multiple antiepileptic drugs, poor background EEG activity, and abnormal neuroimaging seem to have strong predictive values for developing subsequent epilepsy. Therefore, patients with a history of neonatal seizures should be closely followed up to decrease the risk of long-term outcomes and early detection of epilepsy.

Echocardiography may cause significant pain response in preterm infants.

OBJECTIVE: The objective of this study is to evaluate if echocardiographic examination causes any pain response in term and preterm infants. METHODS: Term and preterm neonates who admitted to Neonatal Intensive Care Unit at Gazi University Hospital and Etlik Zubeyde Hanim Training and Research Hospital and were performed echocardiography for any reason were included into the study. Neonates were evaluated before, during and 10 minutes after the examination. Vital signs (heart rate, respiratory rate, blood pressure, transcutaneous oxygen saturation) were recorded. All subjects were also evaluated with Neonatal Infant Pain Scale during the examination. RESULTS: In this study, we evaluated 99 newborn infants. Five infants who received fentanyl treatment were excluded. The heart rate (p = 0.000), respiratory rate (p = 0.000), diastolic blood pressure (p = 0.001) and oxygen saturation (p = 0.000) during the examination were significantly different than the values before and 10 minutes after the examination. Infants whose gestational age ≤32 weeks (n:20) have significantly higher NIPS scores (mean ± SEM = 3.3 ± 0.4) than the infants whose gestational age is greater than 32 weeks (n:71) (mean ± SEM = 2.4 ± 0.2). CONCLUSIONS: Echocardiographic examination which is known as noninvasive and painless causes significant pain in preterm infants.

Newborn hearing screening outcomes during the first decade of the program in a reference hospital from Turkey.

In this study, the authors report the results of a three-stage newborn hearing screening (NHS) program for well babies at the Gazi University Hospital (GUH) in Ankara between 2003 and 2013. GUH-NHS was performed by automated transient evoked otoacoustic emission (a-TEOAE) at the first and second steps and by automated brainstem audiometry (a-ABR) at the third step. The data were analysed to assess not only rate of congenital permanent hearing loss (CPHL), but also the effectiveness of the program during the years. A total of 18,470 well babies were tested. The data showed that coverage ratio for the GUH-born babies was increased and more outside-born babies (OBB) were admitted by time (means 84.31 and 11.28 %, respectively). Mean CPHL was found to be 0.26 %. Mean referral rate was decreased to 0.81 % by a-ABR from 2.16 % by a-TEOAE. Mean of missed cases in any stage of GUH-NHS was 4.88 %. It was seen that neither CPHL nor referral rate, but only ratio of missed ones presented increase in parallel to increment in OBB. This paper first presents that clinically acceptable screening procedures developed in GUH by time, and secondly higher rate of CPHL in Turkey than in the Western countries, and benefits of third stage screening by a-ABR because it prevented referral of 251 children (1.29 %) to the clinical tests. We think that this number is reasonably important regarding not only economical point of view, but also waiting lists in the audiology departments in a developing country, in which audiological service is still limited.

Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome.

Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian_genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.

Tau and S100B proteins as biochemical markers of bilirubin-induced neurotoxicity in term neonates.

We investigated the relationship between total serum bilirubin and serum Tau and S100B protein levels, and predicted a cutoff level of bilirubin-induced neurotoxicity in term newborns. Total serum bilirubin, serum Tau, and S100B levels were measured in 92 jaundiced term newborns. A neurologic examination, electroencephalogram, brainstem auditory-evoked response, and otoacoustic emission were performed in the infants on admission and at age 3 months. Serum Tau (r = 0.921, P < 0.001) and S100B (r = 0.927, P < 0.001) levels were correlated with total serum bilirubin levels in all infants. Serum Tau and S100B protein levels remained at a steady level up to a total serum bilirubin level of 19.1 mg/dL, and then demonstrated a significant increase. Mean total serum bilirubin, serum Tau, and S100B levels of infants who manifested auditory neuropathy, neurologic abnormalities, or electroencephalogram abnormalities were significantly higher than in infants without these abnormalities (P < 0.05). Clinical and laboratory findings of bilirubin-induced neurotoxicity developed after a total serum bilirubin level of 22 mg/dL was reached. Serum levels of Tau and S100B proteins in jaundiced term newborns were strongly correlated with early-phase bilirubin encephalopathy.