What mode of inheritance is most likely responsible for a genetic disorder with complete penetrance affecting two sons and one daughter in a phenotypically normal couple with no other affected relatives in the extended pedigree?

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Differential Diagnosis

  • Single most likely diagnosis
    • Autosomal recessive: This mode of inheritance is most likely because the disorder has complete penetrance, and both sons and a daughter are affected, suggesting that the parents are carriers of the recessive allele. The fact that the parents are phenotypically normal and there are no other affected relatives in the extended pedigree supports this diagnosis.
  • Other Likely diagnoses
    • Autosomal dominant: Although less likely, this mode of inheritance could be considered if one of the parents is a mosaic for the dominant mutation, which would explain the lack of affected relatives in the extended pedigree. However, this would require the mutation to be de novo in the parent, and the likelihood of this occurring is lower.
  • Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)
    • X-linked recessive: This mode of inheritance should be considered because the disorder affects two sons, which could suggest X-linked recessive inheritance. However, the fact that a daughter is also affected makes this less likely, as X-linked recessive disorders typically affect males more frequently than females.
  • Rare diagnoses
    • X-linked dominant: This mode of inheritance is less likely because it would typically affect females more frequently than males, and the fact that two sons are affected suggests otherwise.
    • Mitochondrial inheritance: This mode of inheritance is unlikely because it would typically affect multiple generations and both males and females, often with a maternal pattern of inheritance.
    • Y-linked: This mode of inheritance is highly unlikely because it would only affect males and would be passed from father to son, which is not consistent with the family history presented.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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