Posts by:
Gabriella True

Identification of ultra‑rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

Trifiletti R, Lachman HM, Manusama O, Zheng D, Spalice A, Chiurazzi P, Schornagel A, Serban AM, van Wijck R, Cunningham JL, Swagemakers S, van der Spek PJ. Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing. Sci Rep. 2022 Jun 30;12(1):11106. doi: 10.1038/s41598-022-15279-3. PMID: 35773312. – Open Access

  • The pathological mechanisms are likely heterogeneous, but we hypothesize convergence on one or more biological pathways.
  • Conducted whole exome sequencing (WES) on a U.S. cohort of 386 cases, and whole genome sequencing (WGS) on ten cases from the European Union who were selected because of severe PANS.
  • Focused on identifying potentially deleterious genetic variants that were de novo or ultra‑rare (MAF) < 0.001. Candidate mutations were found in 11 genes (PPM1D, SGCE, PLCG2, NLRC4, CACNA1B, SHANK3, CHK2, GRIN2A, RAG1, GABRG2, and SYNGAP1) in 21 cases, which included two or more unrelated subjects with ultra‑rare variants in four genes.
  • These genes converge into two broad functional categories.
    • One regulates peripheral immune responses and microglia (PPM1D, CHK2, NLRC4, RAG1, PLCG2).
    • The other is expressed primarily at neuronal synapses (SHANK3, SYNGAP1, GRIN2A, GABRG2, CACNA1B, SGCE). Mutations in these neuronal genes are also described in autism spectrum disorder and myoclonus‑dystonia.
  • 12/21 cases developed PANS superimposed on a preexisting neurodevelopmental disorder. Genes in both categories are also highly expressed in the enteric nervous system and the choroid plexus.
  • Thus, genetic variation in PANS candidate genes may function by disrupting peripheral and central immune functions, neurotransmission, and/or the blood‑CSF/brain barriers following stressors such as infection

 

Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease

Citation: Bransfield, R.C. Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease. Healthcare 2022, 10, 1127. https://doi.org/10.3390/healthcare10061127

“In summary, insight into the underlying pathophysiology of Adverse Childhood Events, Post-Traumatic Stress Disorder, and infectious encephalopathies offers expanded treatment opportunities that include psychotherapeutic treatments that help to differentiate safety vs. danger, therapies to improve empowerment, and psychotropic medications to reduce intrusive symptoms and other symptoms, anti-infective treatments, immune-modulating treatments and education for patients and caregivers.“

Paediatric autoimmune neuropsychiatric syndrome in recurrent acute bacterial pharyngitis – a case report

Paediatric autoimmune neuropsychiatric syndrome in recurrent acute bacterial pharyngitis – a case report.  Pepaś, Renata; Przysło, Łukasz; Konopka, Wiesław. Paediatrics and Family Medicine; Warsaw Vol. 18, Iss. 1,  (2022): 84–88. DOI:10.15557/PiMR.2022.0011

Abstract: Pharyngitis and tonsillitis, regardless of their aetiology, are one of the most frequent reasons for visiting a family doctor or a paediatrician. Nearly 85% of pharyngitis cases are viral. It is estimated that bacterial throat infection occurs in 15% of school- age children and in 4–10% of adult patients. Streptococcus pyogenes is the most common cause of bacterial pharyngitis.
PANDAS stands for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The term is used to describe a subgroup of children and adolescents who develop acute obsessive-compulsive disorder or tics as a result of group A streptococcal infection, such as tonsillitis. The aim of the paper is to describe a case of a 4-year-old boy who presented to the Laryngology Clinic due to recurrent tonsillitis, time-correlated with obsessive-compulsive disorder.

Untimely care: How the modern logics of coverage and medicine compromise children’s health and development

M LaRusso, DF Gallego-Pérez, CE Abadía-Barrero. Untimely care: How the modern logics of coverage and medicine compromise children’s health and development, Social Science & Medicine, 2022, 114962, DOI: 10.1016/j.socscimed.2022.114962.

  • Coverage problems for controversial conditions exist across health care systems.
  • Modern medicine fails to support new and controversial conditions like PANS/PANDAS.
  • Despite being insured, many children face barriers to diagnosis and treatment.
  • The modern logics of medicine and coverage fail to provide care in PANS/PANDAS.
  • Failures to care result in developmental disruptions in children with PANS/PANDAS.