• Loss-of-function mutation of filamin A is associated with X-linked inherited form of periventricular nodular heterotopia with or without epilepsy with most individuals affected being female.
Progressive lung involvement in Filamin A (FLNA)-related cerebral periventricular nodular heterotopia (PVNH) has been reported in a limited number of cases.
A mutation in FLNA is the most common cause of periventricular nodular heterotopia (PVNH), but a clear phenotype-genotype correlation has not been established.
Dominant mutations of the X-linked filamin A (<i>FLNA</i>) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia.
Respiratory failure secondary to progressive obstructive lung disease during infancy may be the presenting phenotype of FLNA-associated periventricular nodular heterotopia.
The unique constellation of clinical features in patients with NEDD4L mutations might help clinically distinguish them from patients with other genetic mutations including FLNA, which is a well-known causative gene of periventricular nodular heterotopia.
Mutations of FLNA, an X-linked gene that encodes the cytoskeletal protein filamin A, cause diverse and distinct phenotypes including periventricular nodular heterotopia and otopalatodigital spectrum disorders (OPDS).
Loss-of-function mutations of the FLNA gene cause a neuronal migration disorder defined as X-linked periventricular nodular heterotopia (PNH); gain-of-function mutations are associated with a group of X-linked skeletal dysplasias designed as otopalatodigital (OPD) spectrum.
In stark contrast, two brothers are described with a mild PH presentation, due to a missense mutation (p.Gly2593Glu) inserting a large negatively charged amino acid into the hydrophobic dimerisation interface of FLNA.
Mutations in filamin A (FLNA) or ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) cause periventricular nodular heterotopia, but most patients with this malformation do not have a known aetiology.
Our patient has a FLNA missense mutation (c.220G > A) and presented with cerebral periventricular nodular heterotopia, cardiovascular abnormalities, and pulmonary disease consisting of lobar emphysema of the right middle pulmonary lobe with severe malacia of the right sided bronchus intermedius.
Filaminopathies A caused by mutations in the X-linked FLNA gene are responsible for a wide spectrum of rare diseases including 2 main phenotypes, the X-linked dominant form of periventricular nodular heterotopia (FLNA-PVNH) and the otopalatodigital syndrome spectrum of disorders.
The in-frame deletion in the carboxyl-terminal domain of FLNA caused a phenotype in which PH was associated with skeletal features suggestive of the otopalatodigital syndrome spectrum in boys.
Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in 'Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'.