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Copy number variants (CNVs) remain a major etiological cause of neurodevelopmental delay and congenital malformations. Chromosomal microarray analysis (CMA) represents the gold standard for CNVs molecular characterization. We applied CMA throughout the patient's clinical diagnostic workup, as the patient's medical provider requested. We collected CMA results of 3380 patients enrolled for 5 years (2016-2021). We found 830 CNVs in 719 patients with potential clinical significance, that is, (i) pathogenic, (ii) likely pathogenic, and (iii) variants of uncertain significance (VUS), from which 10.6% (predominantly involving chromosomes 15 and 22) were most likely the final cause underpinning the patients' clinical phenotype. For those associated with neurodevelopmental phenotypes, the rate of pathogenic or likely pathogenic findings among the patients with CNVs was 60.75%. When considering epileptic phenotypes, it was 59%. Interestingly, our protocol identified two gains harbored in 17q21.31 and 9q34.3, internationally classified initially as VUS. However, because of their high frequency, we propose that these two VUS be reclassified as likely benign in this widely heterogeneous phenotypic population. These results support the diagnostic yield efficiency of CMA in characterizing CNVs to define the final molecular cause of genetic diseases in this cohort of Colombian patients, the most significant sample of patients from a Latino population, and define new benign polymorphic CNVs.

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Schuurs-Hoeijmakers syndrome, an autosomal dominant disorder associated with mutations in the PACS1 gene, was initially identified in two unrelated children of European descent from a cohort of individuals with intellectual disabilities. This gene alteration significantly reduced cranial cartilaginous structures, inducing craniofacial alterations predominantly in a dominant-negative fashion. In this paper, we report a novel variant of PACS1 associated with Schuurs-Hoeijmakers syndrome: a boy aged two years and nine months of indigenous descent presenting with motor stereotypies, atypical sensory searches, language delay, and low socio-interactional reciprocity. Whole exome sequencing confirmed the presence of a heterozygous missense mutation c.943C>T p. (Arg315Trp) in the PACS1 gene. The phenotypic profile identified was similar to the other cases of Schuurs-Hoeijmakers syndrome described in the literature. This report highlights the importance of considering the possibility of PACS1 gene alterations and a diagnosis of Schuurs-Hoeijmakers syndrome in patients presenting craniofacial alterations associated with autistic features, psychomotor and language development delay.

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OBJECTIVE: To develop an accurate understanding of outcomes for necrotizing enterocolitis (NEC) to inform parental counseling, clinical care, and research agendas. STUDY DESIGN: A systematic review of recent (January 2010-January 2018) large cohort studies reporting outcomes of infants who developed NEC. Only studies reporting national, regional, or multicenter outcomes of NEC in high income countries were included. Outcomes assessed were mortality, neurodevelopmental outcome, and intestinal failure. Meta-analyses were used to generate summary statistics for these outcomes. RESULTS: Of 1375 abstracts, 38 articles were included. Overall mortality was 23.5% in all neonates with confirmed NEC (Bell stage 2a+) (95% CI 18.5%-28.8%), 34.5% (30.1%-39.2%) for neonates that underwent surgery for NEC, 40.5% (37.2%-43.8%) for extremely low birthweight infants (<1000 g), and 50.9% (38.1%-63.5%) for extremely low birthweight infants with surgical NEC. Studies examining causes of neonatal mortality showed NEC is responsible for around 1 in 10 of all neonatal deaths. Neurodevelopmental disability was reported in 4 studies at between 24.8% and 61.1% (1209 total NEC cases). Three studies reported intestinal failure with an incidence of 15.2%-35.0% (n = 1370). The main limitation of this review is the lack of an agreed definition for diagnosing NEC and the differences in the way that outcomes are reported. CONCLUSIONS: Mortality following NEC remains high. These contemporary data inform clinical care and justify ongoing research efforts. All infants with NEC should have long-term neurodevelopmental assessment. Data on the long-term risk of intestinal failure are limited. TRIAL REGISTRATION: CRD42018094791.

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Introducción: se desconoce por qué las familias y consecuentemente el infante interrumpe o abandona el tratamiento establecido por el Programa de Atención Temprana para los trastornos del neurodesarrollo. Objetivo: Describir las características de las familias que abandonan el tratamiento de estimulación temprana en el centro Senén Casa Regueiro. Material y Métodos: estudio descriptivo, transversal en familias de infantes de 0 a 12 años con trastornos del neurodesarrollo en La Habana Vieja durante el periodo 2014-2015, que considera variables demográficas, sociales y económicas. En el análisis se emplearon las frecuencias absolutas y relativas, la media, la desviación estándar y las pruebas x2. Resultados: la prevalencia de abandono del tratamiento fue del 88,0 por ciento. Los porcentajes de mayor interrupción se presentaron en madres o tutores de 15-18 años (47,20 por ciento, x2 = 10,47 p = 0.0001) y en hijos de padres divorciados (52,00 por ciento). El nivel de escolaridad que mayor porcentaje aportó al problema fue el primario (52,00 por ciento, x2 = 20, 69 p= 0,0000), en familias con mayor número de hijos; de 3-4 hijos (86,40 por ciento, x2 = 29,90 p = 0,00000), que poseían viviendas en malas condiciones (48,00 por ciento x2 = 9,45 p = 0,00021). Los tratamientos más prolongados expresaron mayor porcentaje de abandono (60,00 por ciento, x2 = 3,75 p = 0,053519). Tanto las familias que desertaron del tratamiento, como las que no, presentaron elevados porcentajes de buena satisfacción con el programa (95,20 por ciento y 94,12 por ciento respectivamente). Conclusiones: predominó el abandono al tratamiento en madres cuyos grupos de edades oscilaron entre 15-18 años, divorciadas, en niños con tratamientos más prolongados; destacándose el nivel de escolaridad primario de las madres y las malas condiciones de la vivienda. Asimismo, interrumpieron el tratamiento las familias con mayor número de hijos y menor número de personas con remuneración monetaria(AU)

Introduction: It is unknown why families and consequently, the infant interrupt or abandon the treatment established by the Early Care Program for neurodevelopmental disorders. Objective: To describe the characteristics of families that abandon the early stimulation treatment at the "Senén Casas Regueiro" Center of Comprehensive Pediatric Rehabilitation. Material and Methods: A descriptive, cross-sectional study was conducted in families of infants with neurodevelopmental disorders from 0 to 12 years old in Old Havana, during the period 2014-2015. Demographic, social, and economic variables were considered. Absolute and relative frequencies, the mean, the standard deviation, and the chi-squared tests were used in the analysis. Results: The prevalence of abandonment of treatment was 88.0 percent. The percentages of greatest interruption occurred in mothers or guardians aged 15-18 years (47.20 percent; x2= 10.47; p = 0.0001), and in children of divorced parents (52.00 percent). The level of education that contributed in the highest percentage to the problem was primary schooling (52.00 percent; x2 = 20, 69; p = 0.0000) in families with the largest number of children; families with 3-4 children (86.40 percent; X2 = 29.90; p = 0.00000), who lived in homes in poor conditions (48.00 percent x2 = 9.45; p = 0.00021). Longer treatments expressed a greater percentage of abandonment (60.00 percent; x2 = 3.75; p = 0.053519). Both the families that abandoned the treatment and those that did not do it, showed high percentages of good satisfaction with the program (95.20 percent and 94.12 percent, respectively). Conclusions: Abandonment of treatment predominated in mothers whose age groups ranged between 15-18 years; divorced; in children with more prolonged treatments; highlighting the mothers with primary schooling and poor housing conditions. Likewise, families with a greater number of children and a smaller number of people with monetary remuneration interrupted the treatment(AU)

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Microdeletions in the chromosomal region 17p13.3 are associated with neuronal migration disorders, and PAFAB1H1 is the main gene involved. The largest genomic imbalances, including the YWHAE and CRK genes, cause more severe structural abnormalities of the brain and other associated dysmorphic features. Here, we describe a 3-year-old boy with a microdeletion in 17p13.3 presenting with minor facial dysmorphisms, a cleft palate, neurodevelopmental delay, and behavioral disorder with no structural malformation of the brain. The patient was evaluated by a clinician using a standard protocol. Laboratory investigation included GTG-banding, whole-genome AGH, and array-CGH. Whole-genome AGH and array-CGH analysis identified an estimated 2.1-Mb deletion in the 17p13.3 region showing haploinsufficiency of the YWHAE, CRK, H1C1, and OVCA1 genes and no deletion of PAFAH1B1. The complex gene interaction on brain development and function is illustrated in the genotype-phenotype correlation described here. This report reinforces the importance of the 17p13.3 region in developmental abnormalities and highlights the weak implication of the HIC1 and OVCA1 genes in palatogenesis.

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We report a patient with a terminal 12p deletion associated with autism spectrum disorder (ASD). This 12p13.33 deletion is 1.5Mb in size and encompasses 13 genes (B4GALNT3, CCDC77, ERC1, FBXL14, IQSEC3, KDM5A, LINC00942, LOC574538, NINJ2, RAD52, SLC6A12, SLC6A13 and WNK1). All previous cases reported with partial monosomy of 12p13.33 are associated with neurodevelopmental delay, and we suggest that ERC1, which encodes a regulator of neurotransmitter release, is the best gene candidate contributing to this phenotype as well as to the ASD of our patient.

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