Abstract 23
Category: Clinical Science
At the end of the session, participants will be able to:
- To describe the critical role of the integration of results of genetic testing and postmortem examination in a
multidisciplinary team setting in expanding our knowledge of rare genetic diseases - To discuss the clinical phenotype of THOC-2 related neurodevelopmental disorder.
- To recognize the muscle biopsy findings in THOC-2 related arthrogryposis.
COI Disclosure:
I have a relationship with a for-profit and/or a not-for-profit organization to disclose.
Name of for-profit or not-for-profit organization(s) : National Autopsy Assay Group
Description of relationship(s) : Consultant Neuropathologist (not related to content of presentation)
Presenter
Dr. Leslie Hamilton is a neuropathologist at the Children’s Hospital of Eastern Ontario (CHEO) and The Ottawa Hospital, and
Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of Ottawa. She is board certified
in Anatomic Pathology, Neuropathology and Forensic Pathology. She is the Chair of the Continuing Professional Development
committee with the Canadian Association of Neuropathologists.
Leslie E. Hamilton 1,2, Priya Bhola 1,3, Elizabeth Nizalik 1,2, Brigitte Bonin 1,4, Mark Walker1,4, Erika Bariciak1,5, Julie Hurteau-Miller1,6.
1Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
2Department of Pathology and Laboratory Medicine, Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON.
3Department of Genetics, Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON.
4Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Newborn Care, The Ottawa Hospital, Ottawa, ON.
5Division of Neonatology, Department of Pediatrics, Children’s Hospital of Eastern Ontario (CHEO) and The Ottawa Hospital, Ottawa, ON.
6Department of Medical Imaging, Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON.
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Medical Expert (the integrating role), Collaborator, Health Advocate, Scholar, Professional
Muscle biopsy findings in an infant with arthrogryposis associated with a THOC2 variant: a case report
Abstract
This case report provides the second reported description of muscle biopsy findings in an infant with arthrogryposis associated with a THOC2 variant. THOC2-related neurodevelopmental disorder is caused by deleterious variants in THOC2; this gene encodes a component of the TREX (TRanscription-EXport) complex, which plays a critical role in mRNA processing and export. THOC2-related disorder is characterized by intellectual disability, often associated with seizure disorders, infantile hypotonia, tremors, gait disturbance and growth impairment. More recently, THOC2 variants have been linked to X-linked recessive fetal arthrogryposis multiplex congenita (Cureus 2021; 13(11):e19682; NMD 2023;33(12):978-982). We present a case of an infant who died shortly after birth at 33 weeks gestational age (GA). A fetal ultrasound at 30 weeks GA was significant for arthrogryposis, hydrops and massive polyhydramnios. Genetics consultation and amniocentesis was pursued prior to delivery, and initial genetic testing showed a normal karyotype and rapid aneuploidy detection (RAD). A limited postmortem examination was performed. Biopsy of the quadriceps muscle was significant for moderate variation in myofiber size, and cytoplasmic bodies within several myofibers. Trio whole exome sequencing detected a hemizygous, likely pathogenic variant in THOC2,c.2482-1_2482del . The results of muscle biopsy are identical to those described in a previously reported fetus with arthrogryposis and a THOC2 variant (NMD 2023;33(12):978-982), further validating this neuromuscular phenotype. This case report highlights the critical role that the correlation of whole exome sequencing and postmortem examinations play in expanding our clinical knowledge of rare genetic diseases and their phenotypes.