Distinct Autism Spectrum Disorder Phenotype and Hand-Flapping Stereotypes: Two Siblings with Novel Homozygous Mutation in TRAPPC9 Gene and Literature Review.

Objective: Pathogenic mutations of the TRAPPC9 gene are the rare genetic causes of autosomal recessive intellectual disability (ID). There are several features that are not fully penetrant such as microcephaly, dysmorphic facial features, obesity, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and brain abnormalities in TRAPPC9 mutations. Methods: We performed whole-exome sequencing to evaluate 2 Turkish siblings with ASD and ID born to healthy and consanguineous parents. Parental samples were also analyzed, specifically targeting variants detected in these patients. Results: We present a novel homozygous mutation in the TRAPPC9 gene, c.484G>T (p.Glu162Ter). Additionally, we aim to provide a more comprehensive understanding of the clinical features of a novel homozygous TRAPPC9 mutation. In addition to ID, the siblings in this report suffered from ASD and specific stereotypes as hand-flapping behavior. Conclusion: Although there are inconsistencies in the presentation of ASD in TRAPPC9 mutations, repetitive behaviors (hand-flapping) were typical in our cases and several previous reports. The current mutation was described to cause a homozygous premature termination codon that resulted in the absence of the TRAPPC9 protein. We suggest that TRAPPC9 mutations are not only related to ID but also to ASD and hand-flapping behaviors.

Phenotypic and Brain Imaging Findings Associated With a 10p Proximal Deletion Including the WAC Gene: Case Report and Literature Review.

Microarray-based techniques are an important testing method in etiological studies of intellectual disability and autism spectrum disorder. Interstitial deletion in the p11-p12 region of chromosome 10 is rare, having been reported in just 12 cases to date. Intellectual disability associated with the WAC gene in this region is referred to as DeSanto-Shinawi syndrome . Although all individuals with p11-p12 region of chromosome 10 deletion share a common phenotype involving intellectual disability and dysmorphic features, individuals with DeSanto-Shinawi syndrome usually do not experience the cardiac and neurologic abnormalities or cryptorchidism associated with a 10p11-p12 deletion. With this case report, we aim to expand the phenotypic spectrum of 10p11-p12 deletion. Our patient was a 9-year-old boy with intellectual disability, autism symptoms, dysmorphic features, and behavioral abnormalities. He had no cardiac problems or neurologic symptoms such as hypotonia, feeding difficulties, or seizures. However, he presented cryptorchidism in addition to symptoms that are consistent with DeSanto-Shinawi syndrome. Array comparative genomic hybridization of genomic DNA isolated from a peripheral blood sample revealed a heterozygous deletion in 10p11.23-p12.1, which contains the WAC gene. We discuss our case in the context of a literature review of candidate genes. It is still difficult to establish genotype-phenotype correlations for neurologic, cardiac, and visual symptoms, and cryptorchidism, in individuals with a 10p11-p12 deletion. As more individuals are diagnosed with deletion in this chromosomal region, the associated phenotypes will become clearer.

Olfactory Dysfunction in ß Thalassemia Major Patients Treated With Iron-Chelating Agents.

Ocular and ophthalmological adverse effects may be seen in ß-thalassemia major (BTM) patients treated with regular blood transfusions and iron-chelating agents. We hypothesized that olfactory dysfunction may be present in this population. In this study, we aimed to investigate olfactory dysfunction in patients with BTM and determine the etiological factors. A total of 43 patients with BTM were included in the study. Forty-three patients without any nasal complaints, history of facial trauma, or nasal surgery were included as the controls. All participants had nasal endoscopy. The iron-chelating agents used, their duration of use, as well as hemoglobin and ferritin levels of the BTM patients were recorded. Sniffin' Sticks test (SST) was used to assess olfactory functions, and BTM and control groups were compared for the results. The correlations of SST scores with the other study parameters were analyzed. Eight (18.6%) of 43 patients in the BTM group had hyposmia while none of the patients in the control group had hyposmia (P < .001). Older age, low-hemoglobin level, and longer use of deferoxamine were found to be correlated with olfactory dysfunction. Olfactory dysfunction may be seen in BTM patients treated with iron-chelating agents. The results of this study suggest that screening for olfactory function may be needed in routine follow-up of BTM patients.

Psychiatric symptoms and health-related quality of life in children with epilepsy and their mothers.

PURPOSE: This study evaluated the psychiatric symptoms and health-related quality of life (HRQL) of children with epilepsy and psychiatric symptoms of their mothers, and compared them to those of healthy children and their mothers. This study also explored the influence of the child-related and maternal psychiatric variables and seizure-specific factors on the HRQLs of children with epilepsy according to both the children's and parents' perspectives. METHOD: Ninety-nine children with epilepsy (8 to 17years old), their mothers, and a control group (n=51) participated in this study. The depression and anxiety symptoms of the children were assessed using the Child Depression Inventory (CDI) and the Screen for Child Anxiety-Related Emotional Disorders (SCARED), respectively. The severities of the attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms were assessed via the mother-rated Turgay DSM-IV-Based Child and Adolescent Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S). In addition, the mothers completed the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) to assess their depression and anxiety symptoms, respectively. Child-reported and parent-reported Pediatric Quality of Life Inventories were used to evaluate the HRQLs of the children. RESULTS: The patients exhibited higher inattention and ODD scores than the controls did. With the exception of the child-reported physical health scores, all of the child- and parent-reported HRQL scores were significantly lower in the patient group. According to the regression analysis, the child-related psychiatric and seizure-specific factors, but not the maternal psychiatric factors, were associated with the child's HRQL. The explained variances for the overall HRQL and HRQL subscales were similar between the child-reported (0.373 to 0.654) and parent-reported (0.499 to 0.682) questionnaires. The largest contributors to the total variance were the child-related psychiatric factors for both the child-reported and parent-reported HRQLs by far. CONCLUSION: Epilepsy is associated with a poor psychiatric status and HRQL in childhood. The impact of epilepsy on the HRQL occurs mainly through child-related psychiatric factors. Both the child-reported and parent-reported questionnaires seem to be useful for the evaluation of the HRQL in pediatric epilepsy cases.

Olfactory dysfunction in ß-thalassemia major patients treated with iron-chelating agents.

Ocular and ophthalmologic adverse effects may occur in patients with ß-thalassemia major (BTM) treated regularly with blood transfusions and iron-chelating agents. We hypothesized that olfactory dysfunction may be present in this patient population. We aimed to investigate olfactory dysfunction in patients with BTM and to determine etiologic factors. A total of 43 patients with BTM were included in the study. Forty-three subjects without nasal complaints, history of facial trauma, or nasal surgery were included as the controls. All participants had nasal endoscopy. The use of iron-chelating agents by patients with BTM and their duration of use were recorded, as well as hemoglobin and ferritin levels. The Sniffin' Sticks test (SST) was used to assess olfactory function, comparing results between the BTM and control groups. The correlations of SST scores with the other study parameters were analyzed. Eight (18.6%) of 43 patients in the BTM group and none of the subjects in the control group had hyposmia (p < 0.001). Older age, low hemoglobin level, and longer use of deferoxamine were found to be correlated with olfactory dysfunction. Olfactory dysfunction can occur in patients with BTM treated with iron-chelating agents. The results suggest that screening for olfactory function should be part of the routine follow-up of patients with BTM.

Pediatric Sialadenosis Due to Valproic Acid.

Sialadenosis is a rare entity characterized by bilateral diffuse, painless swelling of the parotid glands. Its etiology is not clear; however, it may occur due to adverse effects of some drugs. To our knowledge, sialadenosis due to valproic acid has not been reported in the literature up to date in any child. In this article, the authors presented a child who developed sialadenosis due to valproic acid, and improved after stopping use of the drug.

A clinical scoring system to predict the development of bronchopulmonary dysplasia.

OBJECTIVE: This study aims to develop a scoring system for the prediction of bronchopulmonary dysplasia (BPD). METHODS: Medical records of 652 infants whose gestational age and birth weight were below 32 weeks and 1,500 g, respectively, and who survived beyond 28th postnatal day were reviewed retrospectively. Logistic regression methods were used to determine the clinical and demographic risk factors within the first 72 hours of life associated with BPD, as well as the weights of these factors on developing BPD. Predictive accuracy of the scoring system was tested prospectively at the same unit. RESULTS: Birth weight, gestational age, gender, presence of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, hypotension were the most important risk factors for BPD. Therefore, a scoring system (BPD-TM score) ranging from 0 to 13 and grouped in four tiers (0-3: low, 4-6: low intermediate, 7-9: high intermediate, and 10-13: high risk) was developed based on these factors. Below the score of 4, 4.1% of infants (18/436), above the score of 9, 100% (29/29) of the infants developed BPD. The score was validated successfully in 172 infants. CONCLUSION: With this easy to use scoring system, one can predict the neonate at risk for BPD at 72 hours of life and direct preventive measures toward these infants.

A pediatric case of ramsay hunt syndrome.

Ramsay Hunt syndrome (RHS) is characterized by facial paralysis, inner ear dysfunction, periauricular pain, and herpetiform vesicles. The reported incidence in children is 2.7/100,000. The pathogenesis involves the reactivation of latent varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. The recovery rate is better in children than in adults. This paper discusses a 12-year-old girl with a rare case of peripheral facial paralysis caused by RHS and reviews the literature.