Familial perisylvian polymicrogyria: A new familial syndrome of cortical maldevelopment

Abstract

Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment.

Specific language impairment: linguistic and neurobiological aspects

“…Polymicrogyria is an anomaly of cortical development in which neurons reach the cort e x but are abnormally distributed, resulting in the formation of multiple small gyri 9 . Perisylvian polymicrogyria has been associated with a wide spectrum of clinical manifestations, such as epilepsy, pseudobulbar signs, cognitive deficits and developmental language disorder or SLI 8,10,11 . The present study has the following objectives: to distinguish linguistic and non-linguistic communicative manifestations of the subtypes of SLI; and to p resent evidence of the correlation between the clinical manifestations of the diff e rent types of SLI and c o rtical abnormalities detected on neuro i m a g i n g exams.…”

“…Wo r s t e r-D ro u g h t 's description fits several of our patients who presented pseudobulbar signs on neurological examination (Table 1). More re c e n t l y, Wo r s t e r-D rought syndrome has been cons i d e red as lying in a continuum with congenital perisylvian syndrome, which is clearly associated with polymicrogyria around the Sylvian fissure 8,10,18,19 .…”

Ictal SPECT in clinical perisylvian syndrome

“…All patients had perisylvian cortical malformations visible on MRI (1). In a multicenter study (5) report on 12 kindreds with familial perisylvian polymicrogyria, variable clinical and radiological patterns were shown among the patients.…”

Malformations of cortical development

“…Guerreiro et al 32 studied several families. One family allowed linkage studies and a new locus was identified and mapped to the chromosome Xq27 33 .…”

“…This entity is the mildest extreme of a broad clinical spectrum of the perisylvian syndrome. Epilepsy is present in less than half of the patients and, when present, is easily controlled with antiepileptic drugs 31,32 . Refractory epilepsy is rarely found in patients with PMG.…”