Whole exome sequencing and transcript analysis discover a novel pathogenic splice site mutation in DCAF17 gene underlying Woodhouse-Sakati syndrome.

Woodhouse-Sakati syndrome (WSS) is an extremely rare multisystemic disorder with neuroendocrine dysfunctions. It is characterized by hypogonadism, alopecia, diabetes mellitus, intellectual disability and progressive extrapyramidal syndrome along with radiological features of small pituitary gland, progressive frontoparietal white matter changes and abnormal accumulation of iron on globus pallidus. WSS is caused by mutations in DCAF17 gene that encodes for DDB1 and CUL4 associated factor 17. In this study, we report a 17-year-old boy with clinical and radiological features of WSS including mild global developmental delay, mild intellectual disability, sensorineural hearing loss, progressive extrapyramidal syndrome, alopecia, hypogonadotropic hypogonadism and dysmorphic features. Whole exome sequencing analysis revealed a novel potentially pathogenic splice donor site variant (c.458+1G>T) on the intron 4 of DCAF17 gene. Transcript analysis revealed splicing ablation resulting in aberrant splicing of exons 3 and 5 and skipping of exon 4 (c.322_458del). This results in a frameshift and is predicted to cause premature termination of protein synthesis resulting in a protein product of length 120 amino acids (p.[Gly108Ilefs*14]). Our study identified a novel pathogenic variant causing WSS in a patient and expands the spectrum of clinical and genetic characteristics of patients with WSS.

Metastatic Pheochromocytoma Diagnosed with 131 I-MIBG SPECT/CT Imaging in a Patient with Pathogenic VHL Mutation.

Pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor arising from chromaffin cells of adrenal medulla with approximate prevalence of 0.1 to 0.6% in patients suffering from hypertension. Hypertensive control followed by surgical resection remains the primary treatment of choice. Although it is considered a slow growing benign tumor, it rarely leads to recurrence of tumor in the lymph nodes, liver, and lungs. Association of benign pheochromocytoma with familial or de novo Von Hippel-Lindau (VHL) mutations is well reported in literature. Here, we report a case of metastatic pheochromocytoma arising from commonly seen benign VHL mutation.

Caregiver distress in schizophrenia and mood disorders: the role of illness-related stressors and caregiver-related factors.

BACKGROUND: Studies using the stress-appraisal-coping model to examine caregiving in schizophrenia and mood disorders are limited. AIM: This study attempted to examine psychological distress among caregivers of persons with schizophrenia and mood disorders using the framework of the stress-coping theory. The impact of illness-related stressors and caregiver-related factors on caregiver-distress was also explored. METHODS: In this cross-sectional study, 176 of the 238 selected outpatients with remitted schizophrenia, bipolar and recurrent depressive disorders identified over a 1-year period underwent standardized assessments of psychopathology and functioning. Assessments of burden, appraisal, coping, social support, neuroticism, familial-cultural variables and psychological distress (as an index of caregiving-outcome) were also carried out among family-caregivers of these persons. RESULTS: High levels of caregiver-burden and caregiver-distress and a mix of positive and negative appraisal, adaptive and maladaptive coping, and high and low levels of perceived support among caregivers characterized the caregiving experience. Univariate analyses revealed that both illness-related stressors (symptom-severity, level of functioning, objective burden) and caregiver-related factors (subjective burden, appraisal, coping, perceived support, family-cohesion, neuroticism, time spent in caregiving) influenced caregiver-distress. However, multivariate analyses demonstrated that caregiver-related factors such neuroticism, perceived support, time spent in caregiving, subjective burden and negative appraisal had a much greater influence on caregiver-distress than illness-related stressors. CONCLUSIONS: Although interactions between illness-related stressors and caregiver attributes appear to determine caregiver-distress, subjective perceptions and other attributes of caregivers may have a greater impact on distress. Therefore, interventions to reduce caregiver-distress should place equal, if not more emphasis on caregiver-related factors which influence distress.

Kerato-lenticular ocular deposits and visual impairment with prolonged chlorpromazine use: A case series.

Chlorpromazine is a low potency "typical" antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects.

Aripiprazole augmentation in highly treatment-resistant obsessive-compulsive disorder - experience from a specialty clinic in India.

OBJECTIVE: To study the effectiveness and tolerability of aripiprazole augmentation in patients with highly treatment-resistant obsessive-compulsive disorder (OCD) in a real-world scenario. METHODS: We conducted a chart review of patients who were initiated on aripiprazole augmentation at a specialty OCD clinic in India between 2004 and 2014. Primary outcome measure was all-cause discontinuation. RESULTS: 23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive-Compulsive Scale. CONCLUSIONS: The study demonstrated, in a real-world setting, that aripiprazole may be a useful augmenting agent in a proportion of patients with highly treatment-resistant OCD. However, side effects may lead to premature discontinuation in many of them.

Effectiveness of Risperidone Augmentation in Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

Risperidone is the most widely used augmenting agent in the treatment of obsessive-compulsive disorder (OCD). However, a recent controlled study found risperidone to be no different from placebo, raising doubts about its effectiveness. In this context, we sought to examine the real-world effectiveness of risperidone from the large database of an OCD clinic in India. A total of 1314 consecutive patients who registered at the OCD clinic between 2004 and 2014 were evaluated with structured interviews and scales. Patients with OCD initiated on risperidone augmentation without concurrent cognitive behavior therapy and who were on stable and adequate doses of serotonin reuptake inhibitors for at least 12 preceding weeks were included for analysis. The primary outcome measure was all-cause discontinuation. Logistic regression was performed to identify the factors predicting improvement with risperidone augmentation. A total of 92 patients were eligible for analysis. Risperidone continued to be used in 23 patients (25%) at the time of last follow-up, and the remaining discontinued either because of ineffectiveness or intolerability. The fall in the Yale-Brown Obsessive-Compulsive Scale scores was significantly greater in patients who continued to take risperidone when compared with those who did not (41.6% vs 3.7%, t = 6.95, P < 0.001). A total of 22 patients (24%) were noted to have at least a 25% reduction on the Yale-Brown Obsessive-Compulsive Scale scores. On regression analysis, no predictors of improvement with risperidone augmentation could be identified. The study demonstrated, in a real-world setting, that risperidone may be a useful augmenting agent in a proportion of patients with partial/poor response to serotonin reuptake inhibitors.

Repetitive Transcranial Magnetic Stimulation Over Presupplementary Motor Area May Not Be Helpful in Treatment-Refractory Obsessive-Compulsive Disorder: A Case Series.

BACKGROUND: A significant proportion of patients with obsessive-compulsive disorder (OCD) fail to improve with standard medication and cognitive behavior therapy. Repetitive transcranial magnetic stimulation (rTMS) has been investigated for its role in treating OCD. Low-frequency rTMS over the presupplementary motor area (pre-SMA) has shown mixed results. Moreover, it has not been studied in highly treatment refractory OCD. We analyzed the outcome of low-frequency rTMS over pre-SMA in OCD patients refractory to multiple serotonin reuptake inhibitors (SRIs), augmenting agents, and cognitive behavior therapy. METHODS: Low-frequency (1-Hz stimulus at 100% motor threshold) rTMS was delivered over the pre-SMA using a previously described protocol. At least 25% reduction Yale-Brown Obsessive Compulsive Scale scores and 2-point reduction in Clinical Global Impression-Severity of Illness scores were used to assess treatment response. RESULTS: Seventeen patients were initiated on rTMS. Three of them dropped out within 9 sittings. Only 1 patient met the criteria for response after 1 month of treatment initiation. No major adverse effects were observed in any of them. LIMITATIONS: The study is a retrospective analysis of outcomes when rTMS was administered as part of routine clinical care. Assessments of the patients were done by trained but different raters, and interrater reliability was not measured. CONCLUSIONS: Low-frequency rTMS over the pre-SMA may not be effective in treatment refractory OCD. Further studies, taking note of the possible reasons for ineffectiveness discussed in the study, may help elucidate the role of rTMS in OCD.

Mirtazapine-associated hyponatremia presenting as delirium.

Though there is ample evidence for the association between selective serotonin reuptake inhibitors and hyponatremia, evidence for the relationship between mirtazapine and hyponatremia is scarce. We present a case of mirtazapine-induced hyponatremia in an adult patient, which was dose related.

Arachnoid cyst masquerades as late onset obsessive-compulsive disorder.

Literature evidence suggests that onset of obsessive-compulsive disorder (OCD) at a later age is usually associated with brain lesions. However, none of previous reports suggest an association between arachnoid cyst and OCD. In this report, we present a case of OCD, starting at the age of 40 years, in which the obsessive symptoms were characteristically associated with fluctuating insight. Investigation revealed an arachnoid cyst, in the area of left fronto-parietal region, with broad base towards the falx.

Long-acting Preparations in Substance Abuse Management: A Review and Update.

Many pharmacological approaches have been used in managing substance use disorders. Conventional pharmacological agents have relatively short durations of action which make them vulnerable to non-adherence and relapse to substance use disorder. To overcome this problem, long-acting preparations have been developed with the aim of reducing the frequency of use and hence improving adherence. This review takes a broad overview of the long-acting preparations available for the management of substance use disorders. The pharmacology, advantages and disadvantages of these preparations are discussed. Many of these preparations hold promise for improving patient outcomes.

Electroconvulsive therapy in the presence of atrial septal defect: a case report.

There is limited literature on the use of electroconvulsive therapy in patient with congenital heart defect. We present a case of a 24-year-old woman with diagnosis of persistent delusion disorder with depression and congenital heart defect of ostium secundum type treated successfully with a course of electroconvulsive therapies.