New mutations

New mutations may account for the presence of a dominant
disorder in a person who does not have a family history of the
disease. New mutations are common in some disorders, such as
achondroplasia, neurofibromatosis (NF1) and tuberous
sclerosis, and rare in others, such as Huntington disease and
myotonic dystrophy. When a disorder arises by new mutation,
the risk of recurrence in future pregnancies for the parents of
the affected child is very small. Care must be taken to exclude
mild manifestations of the condition in one or other parent
before giving this reassurance. This causes no problems in
conditions such as achondroplasia that show little variability,
but can be more difficult in many other conditions, such as
neurofibromatosis and tuberous sclerosis. It is also possible that
an apparently normal parent may carry a germline mutation.
In some cases the mutation will be confined to gonadal tissue,
with the parent being unaffected clinically. In others the
mutation will be present in some somatic cells as well. In
disorders with cutaneous manifestations, such as NF1, this may
lead to segmental or patchy involvement of the skin. In either
case, there will be a considerable risk of recurrence in future
children. A dominant disorder in a person with a negative
family history may alternatively indicate non-paternity.