Predictors of functional outcome in children born without the corpus callosum

Title: Predictors of functional outcome in children born without the corpus callosum: a brain imaging investigation - 51 – DN

Supervisor: Michelle de Haan, Rhonda Booth

Project Description: 
Background
Agenesis of the corpus callosum (ACC) is a rare congenital brain malformation where the corpus callosum (the white matter linking the two hemispheres) fails to develop. ACC is suggested occur in 1:4000 individuals(1) and may present as an isolated finding or be associated with a wide range of chromosomal and neurological conditions(2). As such, individuals with ACC are highly heterogeneous in terms of their presenting problems which can range from mild to severe learning difficulties.

ACC is commonly identified on prenatal ultrasound, but factors that predict outcome are not well understood, and as a result, many parents choose to terminate pregnancy(3). Accurate information about progression and outcome is vital for parents, both at diagnosis and for longer-term care.

Aims/Objectives
This project aims to examine prenatal and postnatal MRI imaging data collected by the Evelina Newborn Imaging Centre (Neonatal Intensive Care Unit, St Thomas’ Hospital) in combination with early neurodevelopmental assessments at follow-up (3, 6, 12, and 24 months) in order to determine neurological predictors of clinical outcomes. Longer-term follow-up of cognitive and neurodevelopmental outcomes will also be collected from families who have consented to further research. The main objective of this project is to improve prognosis for families when ACC is diagnosed prenatally and allow more accurate counselling as well as promote early and targeted support for affected individuals.

Methods
This project will combine a retrospective and prospective approach: (i) analysis of perinatal MRI scans and neurodevelopmental data already available for 36 cases of isolated ACC (collected between 2008-2022) and (ii) data collection to assess current level of cognitive and adaptive functioning for families who consented to longer-term follow-up. MRI datasets of age-matched controls will be used as comparison.
The student will have the opportunity to acquire a diverse set of skills in neuropsychological assessment and MRI analysis, and apply these skills in children of a wide age range and ability levels.

Timeline
Year 1: Review of the literature; training on data analysis pipelines; setting up of prospective study including finalising ethics approval
Year 2: Data collection of prospective cases; analysis of perinatal MRI scans; article writing; complete MPhil/PhD upgrade
Year 3: Final data analysis; dissemination to academia and outside (including patient support groups, public engagement); writing up of thesis and submission

References
(1) Glass HC, Shaw GM, Ma C, Sherr EH: Agenesis of the corpus callosum in California 1983-2003: a population- based study. Am J Med Genet A. 2008, 146A:2495-500. 10.1002/ajmg.a.32418
(2) Shwe WH, Schlatterer SD, Williams J, du Plessis AJ, Mulkey SB. Outcome of agenesis of the corpus callosum diagnosed by fetal MRI. Pediatr Neurol. 2022 Oct;135:44-51. doi: 10.1016/j.pediatrneurol.2022.07.007. Epub 2022 Jul 19. PMID: 35988419.
(3) Santo S, D'Antonio F, Homfray T, et al.: Counseling in fetal medicine: agenesis of the corpus callosum. Ultrasound Obstet Gynecol. 2012, 40:513-21. 10.1002/uog.12315

Contact Information: 
Associate Professor Rhonda Booth