There are several different phenotypes that have been associated with mutations in the FLNAgene.
FLNA mutations have been reported for the otopalatodigital spectrum disorders which include OPD type 1 & type 2 (OPD1 & OPD2), frontometaphyseal dysplasia (FMD) and Melnick-Needles syndrome (MNS). Males are usually more severely affected than females, but females present with variable expressivity. While the primary manifestation is skeletal dysplasia, males may also have a range of congenital anomalies. The most severe types are lethal in males. Normal intelligence is common except for in males with OPD2.
Mutations in the FLNA gene have also been associated with X-linked periventricular heterotopia. This disorder is generally lethal in males and affected females present mid-teens with seizures. This is a neuronal migration disorder in which brain imaging should be used to help establish the diagnosis. Affected females may also have cardiovascular findings, strabismus, psychiatric disorders or learning problems.
There is also an X-linked periventricular heterotopia, Ehlers-Danlos variant. In addition to the heterotopias, these patients have hyperflexible joints, and aortic dilatation or aneurysms.
FLNA mutations have also been reported in cases of X-linked cardiac valvular dysplasia in males characterized by mitral and/or aortic valve regurgitation. Female carriers are asymptomatic.
X-linked chronic idiopathic neuronal intestinal pseudoobstruction is a result of abnormal gastrointestinal motility with recurrent symptoms. All reported affected individuals have been male.