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OBJECTIVES/GOALS: Diagnostic odyssey is the time it can take to a patient for receiving a diagnosis. Diagnostic process in rare diseases can be complex due to the heterogeneity of symptoms and lack of access to care. We aim to evaluate the association between diagnostic odyssey, perceived stress, and access to care, in parents of Puerto Rican patients with a rare disease. METHODS/STUDY POPULATION: We propose a cross-sectional study in parents of 100 children who received an uninformative whole exome sequencing (WES) report during a scheduled appointment with their geneticist. Discussion of WES results during clinical session, followed by a Perceived Stress Scale (PSS-10) and semi-structured interview to explore the experience of access to care during the diagnostic process will be arranged. Observation and interviews will be recorded. Data analysis and descriptive statistics will be calculated using STATA. Statistical associations (OR) will be estimated using generalized linear models at a 5% significance level. RESULTS/ANTICIPATED RESULTS: We expect to find high perceived stress in parents of Puerto Rican pediatric individuals having rare diseases, especially among single mothers. We will be able to identify limited access to care in Puerto Rico, especially in the testing pre-authorization process and long waits for geneticist appointments. Demand for advanced diagnostics is above the number of medical geneticists available in Puerto Rico, which triggers delayed diagnosis, management, and counseling. Therefore, these could affect the health disparities in our population with rare diseases. DISCUSSION/SIGNIFICANCE: This descriptive study will evaluate perceived stress in parents of pediatric patients living a diagnostic odyssey in Puerto Rico. No study has described perceived stress and access to care in this Hispanic population with undiagnosed conditions. Findings will contribute to a deep understanding of diagnostic process and limited access to care.

We are presenting the case of a 6-year-old male patient with progeroid phenotype and severe developmental delay referred to Genetic clinic. Given the complex phenotype an extensive metabolic and genetic evaluation was performed including a whole exome sequencing analysis that showed genetic variants in TTR, RELN, MYH6, PHIP, and SYNE2 genes. Patients’ mother and brother were analyzed for the genetic variants in MYH6, PHIP and RELN. Both had same variants on PHIP and RELN as our patient, with no apparent phenotypical consequences. Physical examination was remarkable for dysmorphism including plagiocephaly, low set and abnormally shaped ears, up slanted palpebral fissures, hypoplastic alae nasi, and a head circumference two standard deviations below the 3(rd) percentile (microcephaly). Other characteristics include wrinkled skin, a broad forehead, sparse eyelashes in lower eyelid, short palpebral fissures, upturned nares, thick lips, right occipital plagiocephaly, overfolded helix and prominent anti-helix, protuberant chest, scaphoid abdomen, digitalized thumbs, and kyphosis due to low muscle tone. The patient presented abnormal EEG with evidence of epileptic discharges. A temporal bone CT showed plagiocephaly with flattening of the right occipital bone. Brain MRI showed callosal agenesis with bilateral colpocephaly with temporal horn dilatation, parahippocampal atrophy, lissencephaly and midbrain hypoplasia. The combination of de novo gene variants mentioned above has never been reported nor correlated as the result of haploinsufficiency mechanisms. Thus, we propose haploinsufficiency and loss of heterozygosity as etiological reasons for this patient phenotype. Further proteomic studies are needed to allocate the extense of genetic influence within the clinical manifestations.