Autosomal dominant (AD) disorders are considered to be the result of de novo pathogenic variants when both biological parents are negative for symptoms of that condition. The risk of recurrence for that couple is often quoted to be “low” or “less than 1%”, due to the rare occurrence of germline mosaicism [1]. Guidance regarding management of possible gonadal mosaicism remains limited despite its implications for reproductive planning in sibling pregnancies. Discuss experience with routine evaluation for paternal germline mosaicism in a sperm donor population following a single report of an apparently de novo dominant disorder in a donor-conceived individual. At California Cryobank, all reports of medical issues in fetuses or offspring conceived using donor semen are documented in an Adverse Outcome Report (AOR) and investigated to assess the etiology and risks to other offspring, the donor and his family. If an offspring’s diagnosis has the potential to increase the risk for a specific disorder in other offspring of that donor, distribution of the donor’s specimens is restricted and relevant individuals are informed of the risk. Adverse Outcome Reports received between January 2016 and November 2018 were reviewed to identify all reports involving one offspring diagnosed with a single-gene disorder that is inherited in an AD manner. Chart documents including, but not limited to, personal and family medical histories, physical examination reports, and genetic test results were reviewed for each donor reported to have an offspring affected with an AD disorder. Thirteen donors were identified with offspring with diagnoses of AD disorders during the time period studied. The offspring diagnoses and subsequent investigations on the semen donors are summarized below (Table 1).Table 1CaseDiagnosisGeneProband’s Test ResultDonor’s Test ResultMethod of testing1Neurofibromatosis, type 1NF1Clinical diagnosis onlyN/A∗Donor was not tested as no mutation was identified in offspringN/A2Cowden syndromePTENSplice site mutationNegativeTargeted testing on semen3Congenital Central Hypoventilation SyndromePHOX2BFrameshift mutationNegativeTargeted testing on semen4CHARGE syndromeCHD7/UnknownClinical diagnosis onlyN/A∗Donor was not tested as no mutation was identified in offspringN/A5Suspected Tuberous SclerosisTSC1/TSC2Negative sequencing of TSC1/TSC2N/A∗Donor was not tested as no mutation was identified in offspringN/A6Tuberous SclerosisTSC2Two variants of unknown significanceNegativeTargeted testing on semen7Neurofibromatosis, type 1NF1Truncating mutationNegativeTargeted testing on semen8Beckwith-Wiedemann SyndromeAltered expression of 11p15Clinical diagnosis onlyN/A∗Donor was not tested as no mutation was identified in offspringN/A9Suspected Skeletal DysplasiaMicro-deletionsTwo microdeletionsNegativeTargeted array on blood10Arthrochalasia Ehlers-Danlos SyndromeCOL1A2Splice site mutationPendingTargeted testing on semen11Tuberous SclerosisTSC2Frameshift mutationNegativeTargeted, sequencing, and del/dup testing on semen12Pseudo-hypoaldosteronism, type 1NR3C2MicrodeletionNegativeTargeted array on semen13Megalencephaly-Capillary Malformation syndromePIK3CAMissense mutationPendingTargeted testing on semen∗ Donor was not tested as no mutation was identified in offspring Open table in a new tab When a donor-conceived individual is diagnosed with a likely de novo pathogenic variant for an autosomal dominant disorder, the risk of recurrence in other offspring in the event of gonadal mosaicism is greater for a gamete donor than in the general population due to the greater-than-average number of potential offspring that may be conceived from one individual.