Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior.

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature.

High-depth next-generation sequencing panel testing in the evaluation of arteriovenous malformations.

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.

Clinical and molecular characteristics of a novel rare variant in in a patient with a developmental disorder, autism, and epilepsy.

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are , encoding the PP2A regulatory B56δ subunit; , encoding the scaffolding Aα subunit; and , encoding the catalytic Cα subunit-in that order of frequency. Patients with a pathogenic mutation in one of these genes, in part, present with overlapping features, such as generalized hypotonia, intellectual and developmental delay, facial dysmorphologies, seizures, and autistic features, and, in part, with opposite features, e.

Whole-Genome and Long-Read Sequencing Identify a Novel Mechanism in Resulting in CANVAS Syndrome.

Objectives: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) results from biallelic intronic pentanucleotide repeats in We describe an adult male proband with progressive imbalance, cerebellar atrophy, somatosensory neuronopathy, and absence of peripheral vestibular function for whom clinical testing demonstrated a heterozygous expansion consistent with an unaffected carrier.

Methods: We performed whole-genome sequencing (WGS) on peripheral blood DNA samples from the proband and his unaffected mother. We performed DNA long-read sequencing and synthesized complementary DNA from RNA using peripheral blood from the proband.

Factors affecting pathways to care for children and adolescents with complex vascular malformations: parental perspectives.

Background: Complex vascular malformations (VMs) are rare disorders that can cause pain, coagulopathy, disfigurement, asymmetric growth, and disability. Patients with complex VMs experience misdiagnosis, delayed diagnosis, delayed or inappropriate treatments, and worsened health. Given the potential consequences of delaying expert care, we must identify the factors that impede or facilitate this access to care.

Road map to developing a fellowship program in a tertiary care hospital.

Background: The American Academy of Pediatrics has identified the need for more subspecialists. Beginning a pediatric pulmonary fellowship program in a tertiary care hospital can be a challenging process. Persistence, perseverance, and working through barriers to education are important strides to take toward achieving this goal.

A 15-year old girl with asthma and lower lobe bronchiectasis.

Wet cough, wheeze, and sputum in an adolescent with evidence for bronchiectasis is an uncommon presentation. The differential diagnosis includes cystic fibrosis (CF), immunodeficiency disorders, complement deficiency, allergic bronchopulmonary aspergillosis, alpha-1 antitrypsin disease, repeated aspiration pneumonia, foreign body, bronchial carcinoid, unresolved right middle lobe pneumonia, and primary ciliary dyskinesia (PCD). The likely diagnosis proceeds from the more to less common in patients with these symptoms.

Genetic diversity of arginine catabolic mobile element in Staphylococcus epidermidis.

Background: The methicillin-resistant Staphylococcus aureus clone USA300 contains a novel mobile genetic element, arginine catabolic mobile element (ACME), that contributes to its enhanced capacity to grow and survive within the host. Although ACME appears to have been transferred into USA300 from S. epidermidis, the genetic diversity of ACME in the latter species remains poorly characterized.

Parapneumonic effusion and empyema in children: retrospective review of the duPont experience.

Management of pediatric parapneumonic effusions and empyema remains controversial. Treatment includes antibiotics, chest tube, fibrinolytic therapy, video-assisted thoracoscopy and debridement, and open thoracotomy and decortication. A retrospective 10-year study was done to identify patient selection variables for specific therapies.

A pseudo-outbreak of Chlamydia trachomatis in a state residential facility: implications for diagnostic testing.

In December 1998, an outbreak of Chlamydia trachomatis genital infections was reported among 18 residents of a state residential facility housing 392 mentally retarded clients. The initial patient tested positive by ligase chain reaction (LCR); 17 others tested positive by culture. Serologic test results for C.