Whole Exome Sequencing Points towards a Multi-Gene Synergistic Action in the Pathogenesis of Congenital Combined Pituitary Hormone Deficiency.

Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for PROP1, LHX3, LHX4 and HESX1 pathogenic variants by Sanger sequencing and for copy number variations by MLPA. In this study, the application of WES in these CPHD newborns revealed the presence of three different heterozygous gene variants in each patient. Specifically in patient 1, the variants BMP4; p.Ala42Pro, GNRH1; p.Arg73Ter and SRA1; p.Gln32Glu, and in patient 2, the SOX9; p.Val95Ile, HS6ST1; p.Arg306Gln, and IL17RD; p.Pro566Ser were identified as candidate gene variants. These findings further support the hypothesis that CPHD constitutes an oligogenic rather than a monogenic disease and that there is a genetic overlap between CPHD and congenital hypogonadotropic hypogonadism.

Alberta Infant Motor Scale (AIMS) Performance of Early-Term Greek Infants: The Impact of Shorter Gestation on Gross Motor Development among "Term-Born" Infants.

Early-term birth (37+0 to 38+6 gestational weeks) may have a negative impact on infants' neurodevelopment compared to delivery at 39 weeks or beyond. The purpose of this study was to evaluate the gross motor development of early-term infants using the Alberta Infant Motor Scale (AIMS). A total of 1087 healthy infants (559 early-term and 528 full-term infants born at 39+0 to 41+6 weeks of gestation) were studied. Mean AIMS scores were compared between the two groups at monthly intervals. The impact of gestational age on total AIMS scores was assessed by linear regression, after adjustment for chronological age, sex and SGA. Mean total AIMS scores, albeit within normal range, were significantly lower in early-term than full-term infants at the 2nd, 6th, 7th, 8th and 12th month of age; differences between groups were within three points. In multivariate regression analysis, a longer gestation by one week had a positive impact on total AIMS score during the first year of life (ß = 0.90; 95% CI 0.45, 1.35). In conclusion, early-term infants exhibit worse gross motor performance during the first year of life in comparison with their full-term peers; however, the differences between the two groups are small.

Development of Lower Extremity Strength in Ambulatory Children With Bilateral Spastic Cerebral Palsy in Comparison With Typically Developing Controls Using Absolute and Normalized to Body Weight Force Values.

This cross-sectional study aimed to examine the development of lower limb voluntary strength in 160 ambulatory patients with bilateral spastic cerebral palsy (CP) (106 diplegics/54 quadriplegics) and 86 typically developing (TD) controls, aged 7-16 years. Handheld dynamometry was used to measure isometric strength of seven muscle groups (hip adductors and abductors, hip extensors and flexors, knee extensors and flexors, and ankle dorsiflexors); absolute force (AF) values in pounds were collected, which were then normalized to body weight (NF). AF values increased with increasing age (p < 0.001 for all muscle groups), whereas NF values decreased through adolescence (p < 0.001 for all muscle groups except for hip abduction where p = 0.022), indicating that increases in weight through adolescence led to decreases in relative force. Both AF and NF values were significantly greater in TD subjects when compared with children with CP in all muscle and all age groups (p < 0.001). Diplegics and quadriplegics demonstrated consistently lower force values than TD subjects for all muscle groups, except for the hip extensors where TD children had similar values with diplegics (p = 0.726) but higher than quadriplegics (p = 0.001). Diplegic patients also exhibited higher values than quadriplegics in all muscles, except for the knee extensors where their difference was only indicative (p = 0.056). The conversion of CP subjects' force values as a percentage of the TD subjects' mean value revealed a pattern of significant muscle strength imbalance between the CP antagonist muscles, documented from the following deficit differences for the CP muscle couples: (hip extensors 13%) / (hip flexors 32%), (adductors 27%) / (abductors 52%), and (knee extensors 37%) / (knee flexors 53%). This pattern was evident in all age groups. Similarly, significant force deficiencies were identified in GMFCS III/IV patients when compared with TD children and GMFCS I/II patients. In this study, we demonstrated that children and adolescents with bilateral CP exhibited lower strength values in lower limb muscles when compared with their TD counterparts. This difference was more prevalent in quadriplegic patients and those with a more severe impairment. An important pattern of muscle strength imbalance between the antagonist muscles of the CP subjects was revealed.

Moderately and Late Preterm Infants: Short- and Long-Term Outcomes From a Registry-Based Cohort.

Background: While most studies on the association of preterm birth and cerebral palsy (CP) have focused on very preterm infants, lately, attention has been paid to moderately preterm [32 to <34 weeks gestational age (GA)] and late preterm infants (34 to <37 weeks GA). Methods: In order to report on the outcomes of a cohort of moderately and late preterm infants, derived from a population-based CP Registry, a comparative analysis of data on 95 moderately preterm infants and 96 late preterm infants out of 1,016 with CP, was performed. Results: Moderately preterm neonates with CP were more likely to have a history of N-ICU admission (p = 0.001) and require respiratory support (p < 0.001) than late preterm neonates. Birth weight was significantly related to early neonatal outcome with children with lower birth weight being more likely to have a history of N-ICU admission [moderately preterm infants (p = 0.006)/late preterm infants (p < 0.001)], to require ventilator support [moderately preterm infants (p = 0.025)/late preterm infants (p = 0.014)] and not to have neonatal seizures [moderately preterm infants (p = 0.044)/late preterm infants (p = 0.263)]. In both subgroups, the majority of children had bilateral spastic CP with moderately preterm infants being more likely to have bilateral spastic CP and less likely to have ataxic CP as compared to late preterm infants (p = 0.006). The prevailing imaging findings were white matter lesions in both subgroups, with statistically significant difference between moderately preterm infants who required ventilator support and mainly presented with this type of lesion vs. those who did not and presented with gray matter lesions, maldevelopments or miscellaneous findings. Gross motor function was also assessed in both subgroups without significant difference. Among late preterm infants, those who needed N-ICU admission and ventilator support as neonates achieved worse fine motor outcomes than those who did not. Conclusions: Low birth weight is associated with early neonatal problems in both moderately and late preterm infants with CP. The majority of children had bilateral spastic CP and white matter lesions in neuroimaging. GMFCS levels were comparable in both subgroups while BFMF was worse in late preterm infants with a history of N-ICU admission and ventilator support.

Maternity blues: risk factors in Greek population and validity of the Greek version of Kennerley and Gath's blues questionnaire.

Aim: To validate the Greek version of Kennerley and Gath's Blues Questionnaire (BQ) and gather further knowledge on maternity blues (MB) associations with certain clinical and sociodemographic factors in Greek population.Material and methods: 116 postpartum women, who met the inclusion criteria, completed the Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the third day after delivery. Sociodemographic and clinical data were also collected.Results: Fifty women (43.1%) experienced severe MB on the third day postpartum. Lower number of previous births, fewer years of marriage, and husband's occupation were found to be associated with MB occurrence. Of them, years of marriage (odds 0.21, p = .001) and husband's occupation in private sector (odds 1.21, p = .04) were independent predictors of MB in logistic regression analysis. Cronbach's α for the total 28-item Greek version of BQ was 0.85. Cluster analysis in our data showed that the optimal number of clusters of BQ items was 4; these four clusters of items presented similarities with the Bartholomew and Horowitz's four-category model of attachment styles (avoidant - dismissing, preoccupied, secure, avoidant - fearful).Conclusions: The Greek version of Blues Questionnaire is a reliable tool for the detection and measurement of MB. Fewer years of marriage and the economic insecurity seem to have strong impact on the occurrence of MB. Further investigation is needed to evaluate whether the phenomenon of MB is associated with parental or mother-to-infant bonding disorders.