Impacts of genetic counseling on hypophosphatasia heterozygotes identified through carrier screening

Hypophosphatasia (HPP) is a mineralization disorder with variable musculoskeletal and dental manifestations. Research suggests people heterozygous for pathogenic/likely pathogenic variants in ALPL may exhibit subtle symptoms, meaning reproductive carrier screening (CS) can yield incidental personal health risks (PHR) and implications for management. Genetic counselors are positioned to discuss these PHRs to patients and their at-risk relatives, and limited data exist on their impact on ALPL heterozygotes' use of this information and their empowerment and satisfaction with the genetic counseling process. We surveyed individuals identified to be ALPL heterozygotes through CS between February 2015 and October 2023. The 29-item survey combined original questions with adapted questions from the Genomics Outcome Scale Short Form and Genetic Counseling Satisfaction Scale, assessing counseling-related satisfaction and empowerment, comprehension and use of information, and personal/familial HPP-related symptoms. Thirty responses were summarized using descriptive statistics and exploratory association analyses, emphasizing effect sizes, 95% confidence intervals (CI), and unadjusted p-values to generate hypotheses for future confirmatory studies. Most participants (n = 25; 83.3%) were glad HPP was included in their CS and felt the genetic counselor's explanation was easy to understand. Higher patient empowerment was associated with the total number of follow-up actions taken (p = <0.001), total number of familial symptoms (p = 0.028), foreknowledge of PHR possibility (p = 0.029), and understanding the counselor's explanation of HPP (p = 0.023). Lower patient empowerment was associated with the total number of personal symptoms (p = 0.044) and feeling that their results were helpful (p = 0.068). Lower patient satisfaction was associated with participants feeling their HPP results were burdensome (p = 0.013). Participants completed a mean of 5.13/18 (28.5%) follow-up actions. These findings highlight the influence pretest PHR education and genetic counseling for results disclosure have on patient satisfaction and empowerment for ALPL heterozygotes identified via CS.