Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review
Eur Child Adolesc Psychiatry. 2021 Oct 5. doi: 10.1007/s00787-021-01883-7. Online ahead of print. ABSTRACT Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of […]
Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy
Brain. 2021 Oct 4:awab369. doi: 10.1093/brain/awab369. Online ahead of print. ABSTRACT The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated […]
ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies
Am J Hum Genet. 2021 Sep 21:S0002-9297(21)00341-4. doi: 10.1016/j.ajhg.2021.09.005. Online ahead of print. ABSTRACT ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. […]
A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion
N Engl J Med. 2021 Sep 30;385(14):1292-1301. doi: 10.1056/NEJMoa2033911. ABSTRACT BACKGROUND: Structural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach. METHODS: We queried worldwide databases of 20,248 families that included children with neurodevelopmental […]
Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial
JAMA Pediatr. 2021 Sep 27. doi: 10.1001/jamapediatrics.2021.3496. Online ahead of print. ABSTRACT IMPORTANCE: Whole-genome sequencing (WGS) shows promise as a first-line genetic test for acutely ill infants, but widespread adoption and implementation requires evidence of an effect on clinical management. OBJECTIVE: To determine the effect of WGS on clinical management in a racially and ethnically […]
Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines
Nat Commun. 2021 Sep 20;12(1):5529. doi: 10.1038/s41467-021-25515-5. ABSTRACT Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients […]
Commentary: Galactosemia Diagnosis by Whole Exome Sequencing Later in Life
Mov Disord Clin Pract. 2021 Sep 3;8(Suppl 1):S40-S41. doi: 10.1002/mdc3.13304. eCollection 2021 Aug. NO ABSTRACT PMID:34514047 | PMC:PMC8414503 | DOI:10.1002/mdc3.13304
Maternal Smoking and Congenital Heart Defects, National Birth Defects Prevention Study, 1997-2011
J Pediatr. 2021 Sep 8:S0022-3476(21)00877-5. doi: 10.1016/j.jpeds.2021.09.005. Online ahead of print. ABSTRACT OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n=8,339) and non-malformed controls (n=11,020) children from all years (1997-2011) of the National Birth Defects […]
Perspectives of Pediatric Providers Regarding Clinical Use of Pharmacogenetics
S D Med. 2021 Jul;74(7):294-301. ABSTRACT INTRODUCTION: A major goal of the current personalized medicine era is to utilize pharmacogenetics (PGx) in order to influence how medications and therapies are prescribed by providers. However, disparities for prescribing medications between adults and children exist. Research has shown that children are not just small adults and there […]
Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth
Sci Rep. 2021 Aug 24;11(1):17115. doi: 10.1038/s41598-021-96374-9. ABSTRACT Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has […]