P431: Expanding the genotypic and phenotypic description of an ultra-rare condition: A neonatal presentation of spondylo-ocular syndrome

anus with rectovaginal fistula.She was suspected to have VACTERL association; echocardiogram revealed patent ductus arteriosus (PDA) and patent foramen ovale and abdominal ultrasound showed horseshoe kidneys.Hand radiographs showed bilateral hypoplastic thumbs, bilateral clinodactyly of index fingers, and right 5th finger.Head computed tomography confirmed left coronal craniosynostosis.Brain and spine magnetic resonance imaging studies were unremarkable.Spinal radiographs showed fusion of S4-S5 vertebrae.Audiology evaluation showed moderate bilateral conductive hearing loss at age 3 years, likely related to recurrent ear infections and middle ear effusion.Her endocrine evaluation for short stature and low body weight at age 7 years was unremarkable.The proband exhibited speech/language delay and learning difficulties and was diagnosed with attention-deficit/hyperactivity disorder.Diagnostic Workup: A chromosomal SNV microarray was normal.Because of the proband's physical findings and the suspected VACTERL association, a chromosomal breakage test (CBT) on blood lymphoblasts was ordered and showed slightly increased breaks and radial forms but was insufficient to confirm the diagnosis of FA.Subsequently, CBT was performed on skin fibroblasts which also showed inconclusive results.FA gene panel uncovered a de novo RAD51 c.884A>G; p.(His295Arg) variant.Based on ACMG/AMP criteria, this variant was interpreted as likely pathogenic based on PS2, PM2, PM6, PP3 and PP4 scores, establishing the RAD1-related FA diagnosis.