Recurrence of perinatal XXXX in sibships: parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance.

@entity1 @entity6926
PURPOSE: Recurrence of @entity6926 in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. METHODS: We measured the recurrence rate of @entity6926 after the birth of an affected @entity1 . We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected @entity1 were born, we identified mutations and determined the proportion that resulted from recessive inheritance. RESULTS: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected @entity1 was 16%. In 37 families with two affected @entity1 , 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected @entity1 was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. CONCLUSIONS: In most populations, recurrence of @entity6926 usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of @entity6926 will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
