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.
Children With PANS May Manifest POTS

Chan A, Gao J, Houston M, Willett T, Farhadian B, Silverman M, Tran P, Jaradeh S, Thienemann M, Frankovich J. Children With PANS May Manifest POTS. Frontiers in Neurology. Vol 13, 2022 DOI: 10.3389/fneur.2022.819636

  • 204 patients: mean age of PANS onset was 8.6 years, male sex (60%), non-Hispanic White (78%).
  • Evidence of POTS was observed in 19/204 patients (9%). 5/19 have persistent POTS
  • Those with PANS & POTS were more likely to have
    • comorbid joint hypermobility (63 vs 37%, p = 0.04)
    • chronic fatigue (42 vs 18%, p = 0.03)
    • family history of chronic fatigue, POTS, palpitations and syncope
  • Showed a PANS flare was significantly associated with an exacerbation of POTS symptoms (OR 3.3, 95% CI 1.4–7.6, p < 0.01)
Unexplained post-acute infection syndromes

Choutka, J., Jansari, V., Hornig, M. et al. Unexplained post-acute infection syndromes. Nat Med 28, 911–923 (2022). https://doi.org/10.1038/s41591-022-01810-6

“SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.”

Understanding parental stress among parents of children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) in Sweden
Noam Ringer & Lise Roll-Pettersson (2022) Understanding parental stress among parents of children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) in Sweden, International Journal of Qualitative Studies on Health and Well-being, 17:1, DOI:10.1080/17482631.2022.2080906
The study illuminates how parents’ perceptions of the child’s symptoms, parents’ strategies for managing problems, as well as experiences related to healthcare providers, may increase or decrease parental stress.
  • The analysis of interviews resulted in five identified categories, which together reflect aspects related to parental stress in parents of a child with PANS.
  • The first three categories reflect parents’ appraisals related to the condition:
    • “Being effected by PANS”
    • “Experiencing PANS over and over again
    • “Having no control”
  • The fourth category, “Obtaining medical treatment is challenging”, entails appraisals related to contact with clinicians
  • The fifth category, “Managing problems”, consists of strategies parents apply in order to manage problems related to having a child with PANS

 

Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study

Ang Zhou, Elina Hyppönen, Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study, International Journal of Epidemiology, 2022;, dyac087, https://doi.org/10.1093/ije/dyac087

Conclusion: The observed association between 25(OH)D and CRP is likely to be caused by vitamin D deficiency. Correction of low vitamin D status may reduce chronic inflammation.

See Related Article – https://www.medicalnewstoday.com/articles/vitamin-d-supplements-may-help-reduce-chronic-inflammation-study-finds#Low-vitamin-D,-more-inflammation