P489: A case of bilateral congenital hypoplastic testes leading to an unexpected diagnosis of X-linked trichothiodystrophy

retinal abnormalities.As less than 40 patients have been described worldwide the phenotype is still evolving.Here we present a case with progressive neurological symptoms.Case Presentation: We present a 15-year-old female with a complex clinical history, who was diagnosed with familial hemophagocytic lymphohistiocytosis (HLH) in infancy, leading to bone marrow transplant at age 4 months.Neurologically, she developed nystagmus at 6 months of age, followed by global developmental delay, ADHD and abnormal movements suggestive of chorea, which have remained stable.Brain imaging showed calcifications in the basal ganglia and subcortical white matter of the frontal lobes.She has gait ataxia and fine motor difficulties, including dysgraphia.Additionally, she has short stature, facial dysmorphism, atypical dentition, primary ovarian insufficiency, history of multiple fractures, atypical bony development in feet, and hypercholesterolemia. Her family history is notable for a brother who died in infancy from HLH and two healthy siblings.Diagnostic Workup: The patient underwent extensive genetic testing, including genome sequencing, mitochondrial DNA sequencing, chromosomal microarray, STXBP2 variant analysis, Correlagen ZAP70 DNA sequencing test which were all taken from pre-bone marrow transplant DNA and all were negative.Genome sequencing was also performed from skin fibroblasts and was negative.However, a research reanalysis of genomic data revealed novel biallelic missense VPS45 variants, c.652C>T and c.1157G>A, in the proband which were also confirmed by Sanger sequencing.Parental testing demonstrated that the variants were inherited in trans from unaffected heterozygous parents.Additionally, the same variants were also seen in the whole exome data of the affected deceased brother.