Three Generations of FLNA-Associated Periventricular Nodular Heterotopia

Abstract

We present a family with 3 generations of FLNA gene-associated periventricular nodular heterotopia (PVNH), with a unique presentation in a fetus with multiple neurologic malformations. Neurologic abnormalities were noted on routine fetal imaging for a 33-year-old G1P0 woman; absence of the corpus callosum and PVNH was confirmed on follow-up MRI. This prompted genetic evaluation, revealing a nonsense mutation in the FLNA gene. Familial genetic analysis and neuroimaging revealed the same variant and MRI evidence of PVNH in the fetus’s asymptomatic mother, and maternal grandmother, who had a long history of seizure disorder. Such phenotypic variability within a single family demonstrates the spectrum of PVNH and the importance of genetic counseling for patients with PVNH. This case also adds to existing literature on the rare but not unique presentation of FLNA-associated fetal malformations.

Sustained generation of neurons destined for neocortex with oxidative metabolic upregulation upon filamin abrogation

“… 22 , 26 , 27 , 28 Although some affected individuals may present mild cognitive, behavioral, or reading deficits, 29 , 30 , 31 the condition can often be asymptomatic or associated with little or no impairments on intellectual abilities. 20 , 21 , 22 , 23 , 32 , 33 In line with the minimal cognitive deficits, alterations in neocortical structures of the affected brains are often insignificant despite the presence of a large number of periventricular ectopic neurons, 29 , 34 , 35 , 36 , 37 though a recent report of whole-brain multimodal MRI study suggested an association of PH with cortical thickening. 38 Overall, the generation of periventricular neurons has minimal or very mild impairments to canonical developmental programs for neocortical neurogenesis and neuronal migration.…”