Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study.

Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0-18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p < 0.001) in tricipital and subcapsular skinfold thickness, with an upward trend of height SDS and a downward trend of BMI SDS, was observed. Infants who started GH before 15 months of age started walking at a median of 18.0 [17.0-19.5] months vs. 36.6 [36.3-37.8] months for those who began treatment with GH after 15 months of age (p = 0.024). Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.

Identification of a de novo splicing variant in the Coffin-Siris gene, SMARCE1, in a patient with Angelman-like syndrome.

BACKGROUND: Patients affected by Angelman syndrome (AS) present severe intellectual disability, lack of speech, ataxia, seizures, abnormal electroencephalography (EEG), and a characteristic behavioral phenotype. Around 10% of patients with a clinical diagnosis of AS (AS-like) do not have an identifiable molecular defect. Some of these patients harbor alternative genetic defects that present overlapping features with AS. METHODS: Trio whole-exome sequence was performed on patient and parent's DNA extracted from peripheral blood. Exome data were filtered according to a de novo autosomal dominant inheritance. cDNA analysis was carried out to assess the effect of the splice site variant. RESULTS: We identified a novel heterozygous SMARCE1 splicing variant that leads to an exon skipping in a patient with an Angelman-like phenotype. Missense variants in the SMARCE1 gene are known to cause Coffin-Siris syndrome (CSS), which is a rare congenital syndrome. Clinical reevaluation of the patient confirmed the presence of characteristic clinical features of CSS, many of them overlapping with AS. CONCLUSIONS: Taking into account the novel finding reported in this study, we consider that CSS should be added to the expanding list of differential diagnoses for AS.

Comparación Directa de Niñas Adoptadas en China y Europa del Este: Ansiedad, Hiperactividad/Impulsividad, Inatención y Conductas Desafiantes / A Direct Comparison of Girls Adopted from China and Eastern Europe: Anxiety, Hyperactivity/Impulsivity, Inattention and Defiant Behaviours

Previous research looking at adopted children has shown that children adopted from Eastern Europe (EE) are more likely to show inattention and hyperactivity/impulsivity whereas girls adopted from China (CH) tend to have normative adjustment scores, although as they grow up, internalising behaviours might increase. We directly compare parental ratings of the SNAP-IV (Hyperactivity/Inattention) and SCARED (Anxiety) of girls adopted from CH (n = 42), EE (n = 34) and other countries (n = 32). EE were more likely to show inattention, hyperactivity/impulsivity and defiant behaviours than CH, independent of age at adoption and number of siblings. The age of the child only had a significant effect on defiant behaviours. No significant differences in anxiety were observed between groups. Overall anxiety levels were related to hyperactivity/impulsivity. Specific factors related to adoption in each region might account for differential levels in inattention, hyperactivity/impulsivity and defiant behaviours and should be taken into account to aid the adjustment of adoptees (AU)

Estudios previos sobre menores adoptados han mostrado que los menores adoptados en Europa del Este (EE) tienen más probabilidades de mostrar inatención e hiperactividad/ impulsividad mientras que las niñas adoptadas en China (CH) suelen obtener puntuaciones normales en adaptación, aunque a medida que crecen, puede que aumenten las conductas internalizantes. Comparamos directamente las puntuaciones obtenidas en el SNAP-IV (Hiperactividad/Inatención) y el SCARED (Ansiedad) por niñas adoptadas en CH (n = 42), EE (n = 34) y en otros países (n = 32). EE muestran más inatención, hiperactividad/ impulsividad y conductas desafiantes que CH, independientemente de la edad de adopción y del número de hermanos. La edad de adopción solo tiene un efecto significativo sobre las conductas desafiantes. No se observan diferencias significativas en ansiedad entre los grupos. En general, los niveles de ansiedad están relacionados con la hiperactividad/impulsividad. Factores específicos relacionados con la adopción en cada una de estas regiones podrían explicar parte de las diferencias en inatención, hiperactividad/inatención y conductas desafiantes y se deberían tener en cuenta para potenciar la adaptación de los adoptados (AU)

ADHD-like symptoms and attachment in internationally adopted children.

Internationally adopted children seem to be more likely to show ADHD-like symptoms than non-adopted children. The aims of this study were to explore the existence of ADHD-like symptoms and/or diagnosis in a sample of internationally adopted children depending on their country of origin and to describe the links that may exist between the display of these symptoms and observed narrative-based attachment patterns. A Catalan sample of 58 adopted children aged 7-8 (24 from Eastern Europe, 23 from China, and 11 from Ethiopia) was assessed with the Behavioral Assessment System for Children to identify ADHD-like symptoms, and the Friends and Family Interview to identify children's' attachment patterns. Results indicated that children adopted from Eastern Europe showed a trend toward more hyperactivity and significantly more attention problems than girls adopted from China. Children with a secure attachment showed significantly less attention problems and a trend toward less hyperactivity. More studies focusing on the etiology and treatment of these symptoms in adopted children are needed.

Microdeletion and microduplication 22q11.2 screening in 295 patients with clinical features of DiGeorge/Velocardiofacial syndrome.

The 22q11.2 region is susceptible to chromosomal rearrangements, leading to various types of congenital malformation and mental retardation. The most common anomaly is 22q11.2 microdeletion, associated with DiGeorge/Velocardiofacial syndrome (DG/VCFS). Recently the microduplication 22q11.2 syndrome has been identified. Some clinical features in patients with this new chromosomal disorder present a substantial overlap with DG/VCFS. The aim of this hospital-based study was to evaluate the incidence of deletions and duplications on 22q11.2 in patients with DG/VCFS features. We investigated a group of 295 patients with widely variable manifestations associated with DG/VCFS. Along with the clinical diagnoses different anomalies were noted such as conotruncal cardiac anomaly, velopharyngeal insufficiency, characteristic facial dysmorphic features, language impairment, developmental delay/learning difficulties, and immunologic anomalies or thymic hypoplasia. Laboratory studies included conventional cytogenetic and FISH testing. Metaphase and interphase cells were analyzed for the presence of 22q11.2 microdeletion or microduplication. There were 12 patients who carried 22q11.2 microdeletion and no microduplication in the region was identified. Other chromosomal anomalies were reported in five patients with an overlapped DG/VCFS phenotype. All patients with 22q11.2 microdeletion showed a characteristic phenotype of DG/VCFS. We did not identify 22q11.2 microduplication, suggesting that this is a rare event in patients with DG/VCFS features.