Detailed clinical, ophthalmological, and molecular studies were performed on a multigeneration family in which there were many subjects with
type 1 neurofibromatosis, a common autosomal dominant disorder. Affected family members displayed a wide range of clinical findings including, in two subjects, features seen in
Noonan syndrome (triangular
facies, downward slanting palpebral fissures,
micrognathia, short stature, and
learning disability). Subjects have been described previously whose features have overlapped with
neurofibromatosis and
Noonan syndrome, and it has been suggested that these persons might represent a separate condition.
DNA haplotype analysis showed linkage of the
neurofibromatosis phenotype seen in this family to the proximal long arm of chromosome 17 in the region where the
type 1 neurofibromatosis gene has been mapped. These results imply that the Noonan phenotype seen in some patients with
type 1 neurofibromatosis might be the result of variable or variant expression of the
neurofibromatosis gene on chromosome 17. The possible role of non-specific factors, such as fetal
hypotonia, in producing the
neurofibromatosis-Noonan phenotype needs further investigation. The availability of closely linked and intragenic molecular markers for
neurofibromatosis could potentially be useful in the diagnosis and characterisation of patients and families with atypical forms of
neurofibromatosis.