Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades. In general, the cognitive profile in CS is characterized by intellectual disability ranging from mild to severe impairment. The first published descriptions of behavior in CS children underlined the presence of irritability and shyness at younger ages with sociable personality and good empathic skills after 4-5 years of age, however some recent studies have reported autistic traits. We report on a 7-year-old boy heterozygous for a rare duplication of codon 37 (p.E37dup) in HRAS, manifesting impaired social interaction and non-verbal communication and with circumscribed interests. These additional features improve phenotype delineation in individuals with rare HRAS mutations, facilitating the development of specific behavioral treatments which could lead to improvement in cases of autism spectrum disorder.

Rett\'s syndrome is a rare condition affecting only the girl child. It presents as a pervasive developmental disorder with a remarkable behavioural phenotype. The cause for this remains unknown but genetic factors and brain dysfunction have been implicated. This case report emphasises the importance of being aware of rare yet significant disorders of interest to neuro-developmental psychiatrists.

Due to co-morbidities and treatment resistant nature of pervasive developmental disorder (PDD), diverse combinations of regimens have been tried. This retrospective study aimed to explore adjunctive use of aripiprazole in children with PDD. Changes in illness severity were measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) in 14 aripiprazole-treated patients with PDD. Improvement of illness severity was observed after aripiprazole add-on (5.8±0.8 to 4.9±1.0, Z=-2.75, p=0.001). Mean dosage was 7.7 mg/day [standard deviation (SD) 3.3, range 5-15]. A higher mean dosage was observed in group with improvement in symptoms (t=-2.33, df =12, p=0.004). The target symptoms most effectively improved after using aripiprazole were positive psychotic symptoms (mean CGI-I: 2.0±1.4, 3 responders/4 patients, 75% response) followed by aggressive behavior (2.5±1.7, 3/4, 75%), self-injurious behavior (2.0±1.0, 2/3, 67%), stereotypic behavior (2.7±1.2, 2/3, 67%), tic (2.8±1.0, 2/4, 50%), irritability (3.5±2.1, 1/2, 50%), obsessive behavior (2.5±2.1, 1/3, 33%), hyperactivity (3.4±1.6, 3/7, 43%) and mood fluctuation (3, 0/1, no response). Five patients (35%) discontinued aripiprazole due to treatment-emergent adverse effects (akathisia, insomnia, withdrawal). The results of this study suggest that aripiprazole augmentation may be used safely in maladaptive behaviors of some populations of PDD. However, future studies are required to confirm these preliminary findings.