ZDHHC15 as a candidate gene for autism spectrum disorder.

The phenotypic repercussion of ZDHHC15 haploinsufficiency is not well-known. This gene was initially suggested as a candidate for X-linked mental retardation, but such an association was later questioned. We studied a multiplex family with three members with autism spectrum disorder (ASD) by array CGH, karyotype, exome sequencing and X-chromosome inactivation patterns. Medical history interviews, cognitive and physical examinations, and sensory profiling were also assessed. The three family members with ASD (with normal cognitive abilities and an abnormal sensory profile) were the only carriers of a 1.7 Mb deletion in the long arm of chromosome X, involving: ZDHHC15, MAGEE2, PBDC1, MAGEE1, MIR384 and MIR325. The normal chromosome X was preferentially inactivated in female carriers, and the whole exome sequencing of an affected family member did not reveal any additional genetic variant that could explain the phenotype. Thus, in the present family, ASD segregates with a deletion on chromosome X that includes ZDHHC15. Considering our results together with gene data (regarding function, expression, conservation and animal/cellular models), ZDHHC15 is a candidate gene for ASD. Emerging evidence also suggests that this gene could be associated with other neurodevelopmental disorders, with incomplete penetrance and variable expressivity.

GLYT1 encephalopathy: Further delineation of disease phenotype and discussion of pathophysiological mechanisms.

GLYT1 encephalopathy is a form of glycine encephalopathy caused by disturbance of glycine transport. The phenotypic spectrum of the disease has not yet been completely described, as only four unrelated families with the disorder have been reported to date. Common features of affected patients include neonatal hypotonia, respiratory failure, encephalopathy, myoclonic jerks, dysmorphic features, and musculoeskeletal anomalies. All reported affected patients harbor biallelic genetic variants in SLC6A9. SNP array together with Sanger sequencing were performed in a newborn with arthrogryposis and severe neurological impairment. The novel genetic variant c.997delC in SLC6A9 was detected in homozygous state in the patient. At protein level, the predicted change is p.(Arg333Alafs*3), which most probably results in a loss of protein function. The variant cosegregated with the disease in the family. A subsequent pregnancy with ultrasound anomalies was also affected. The proband presented the core phenotypic features of GLYT1 encephalopathy, but also a burst suppression pattern on the electroencephalogram, a clinical feature not previously associated with the disorder. Our results suggest that the appearance of this pattern correlates with higher cerebrospinal fluid glycine levels and cerebrospinal fluid/plasma glycine ratios. A detailed discussion on the possible pathophysiological mechanisms of the disorder is also provided.

Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction.

AIM: To evaluate the neurodevelopmental outcome at 12 months' corrected age in preterm infants with and without severe intrauterine growth restriction. METHODS: This prospective follow-up study included 37 infants with severe intrauterine growth restriction and 36 appropriate-for-gestational-age infants born between 26 and 34 weeks. Neonatal and infant data were prospectively recorded. Infants were assessed at 12 ± 2 months' corrected age with the Hammersmith Infant Neurological Examination and the Bayley Scale for Infant Development version-II. RESULTS: Both groups were similar in demographic characteristics and perinatal status. No significant differences in neurodevelopmental performance were found. The mental development index was 98.8 (SD 9.0) vs 98.4 (SD 13.1) (p = 0.9) and the psychomotor development index was 91.7 (SD 9.9) vs 95.5 (SD 13.4) (p = 0.2) for the study and reference groups respectively. Neurological assessment showed no significant differences between the two groups. CONCLUSION: Although the study group showed a non-significant trend towards a lower score in the psychomotor development index than the reference group, significant differences at 12 months could not be demonstrated. IUGR infants continued to have significantly lower weight, length and head circumference at 1 year.

Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies.

OBJECTIVE: This study was undertaken to document pregnancy and infant outcome after cord coagulation with laser and/or bipolar as a technique for selective feticide in complicated monochorionic multiple pregnancies. STUDY DESIGN: Prospective follow-up study in 2 tertiary fetal medicine centers. RESULTS: Eighty cases were included in the study (73 twins, 7 triplets). The survival rate was 83% (72/87). There were 9 intrauterine fetal deaths (10%), 5 within 24 hours and 4 between 4 and 10 weeks after the procedure. There was 1 termination of pregnancy because of chorioamnionitis. Median gestational age at delivery was 35.4 weeks, with 79% of patients delivering after 32 weeks. Preterm prelabor rupture of the membranes before 25 weeks accounted for all perinatal deaths (n = 5). Of the children older than 1 year of age (n = 67), 62 (92%) have a normal development. CONCLUSION: Cord coagulation is an effective method for selective feticide in monochorionic multiple pregnancies.

Staff perceptions on Newborn Individualized Developmental Care and Assessment Program (NIDCAP) during its implementation in two Spanish neonatal units.

BACKGROUND: The implementation of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) requires great effort. Few studies evaluating staff perception of NIDCAP exist, especially in Southern Europe, and these few studies usually have a low representation of the medical staff. AIMS: Exploration of staff perception (neonatologists, nurses and nursing assistants) of NIDCAP during its implementation and their attitude towards it and intention to put it into practice. STUDY DESIGN: This study is a descriptive survey measuring staff perceptions of NIDCAP and its effects on their work in two Spanish neonatal level III intensive care units (NICUs). Validated questionnaires were distributed to neonatologists, nurses and nursing assistants of which 305 were completed (response rate: 85%). RESULT: Virtually all the items which assess the infant's well being and the parents' role received a positive evaluation. However, three items got slightly negative evaluations: NIDCAP was more time consuming and nurses' working conditions and lighting in the unit were less optimal than in earlier practices. The professionals also had a positive attitude and a willingness to use the NIDCAP. Neonatologists perceived NIDCAP more positively than the nursing staff with statistically significant differences. CONCLUSION: The neonatal unit staff in two Spanish NICUs perceived NIDCAP positively. This assessment is more positive for neonatologists than for nurses.

Necessary resources and barriers perceived by professionals in the implementation of the NIDCAP.

BACKGROUND: The implementation of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) requires a significant effort from all professionals involved. AIM: To determine the necessary requirements and barriers perceived by health professionals in the implementation of the NIDCAP. STUDY DESIGN: A questionnaire covering requirements and obstacles perceived in the implementation of the NIDCAP was developed and validated in two Spanish level III neonatal intensive care units. The questionnaire was answered by 305 health professionals (response rate of 85%). RESULTS: The requirements identified in the questionnaire were considered by most respondents as necessary to implementing the NIDCAP, especially more time, education, and staff. Nurses, compared to doctors, thought that more staff was necessary (93% vs. 74%; p < .01). The main obstacle identified in the survey was lack of coordination among different professionals (77%), followed by noise level in the unit (35%). Doctors, in comparison to nurses, considered noise level (61% vs. 23%; p < .01) and nursing staff (56% vs. 29%; p = .05) the most relevant obstacles to NIDCAP implementation. The more experienced professionals perceived their own colleagues as an obstacle, particularly among nursing staff. CONCLUSIONS: The implementation of the NIDCAP requires a series of conditions that confirm it is not a trivial process but rather a somewhat laborious one. The lack of coordination among different professionals is often considered the main obstacle.

Prevalence of neonatal ultrasound brain lesions in premature infants with and without intrauterine growth restriction.

AIM: To compare the prevalence of transient periventricular echodensities (TPE), periventricular leukomalacia (PVL) and haemorrhagic brain lesions (HBL) in singleton intrauterine growth-restricted (IUGR) infants and in those appropriate for gestational age (AGA). METHODS: Thirty-five IUGR and 35 AGA singleton infants born between 24- and 34-week gestational age were studied. The presence of TPE, PVL and HBL was assessed with ultrasound (US) at day 3 (US-I), 2 weeks (US-II) after delivery and at term-equivalent age (US-III). RESULTS: IUGR neonates had an increased prevalence of TPE at US-I (18/35 vs. 8/35, p= 0.02) and an increased prevalence of PVL at US-II (8/32 vs. 1/31, p = 0.03) and US-III (8/29 vs. 1/29, p = 0.02). No significant differences in the prevalence of HBL were found between the two groups. CONCLUSIONS: IUGR is associated with an increased prevalence of white matter damage on US brain scans in preterm neonates.