Partial agenesis of the corpus callosum in a patient with juvenile myoclonic epilepsy.

We describe a patient who presented at our epilepsy-monitoring unit with myoclonic jerks, and was diagnosed with juvenile myoclonic epilepsy (JME). Imaging of his brain revealed partial agenesis of the corpus callosum (ACC). We discuss the known genetic basis of both JME and ACC, as well as the role of the corpus callosum (CC) in primary generalized epilepsy. Both JME and ACC are associated with gene loci on chromosome 15q14. Structural brain abnormalities other than ACC, such as atrophy of the corpus callosum have been reported in patients with JME. ACC has been associated with seizures, suggesting an anti-epileptogenic role of the corpus callosum. On the other hand, corpus callosotomy is used to treat refractory idiopathic generalized epilepsy, which shows that the corpus callosum may play an epileptogenic role. The occurrence of both these conditions in one patient raises the question of whether they are purely coincidental or if there is a common basis for both. Several issues need to be addressed: the mechanism of seizure generalization in the setting of partial ACC, the possible role of other structures in generalization, and whether the ACC contributes to epileptogenesis as a result of the lack of a normal CC inhibitory effect.     

Spectrum of corpus callosum agenesis

Magnetic resonance imaging and clinical features of 16 children with agenesis of the corpus callosum are reviewed. The patients were classified in three groups. Eight children had agenesis of the corpus callosum without substantial involvement of other brain areas. This group included patients with interhemispheric cyst, lipoma, or partial agenesis (hypogenesis) of the corpus callosum. Four patients in the second group manifested severe telencephalic dysgenesis in addition to agenesis of the corpus callosum. In the third group, agenesis of the corpus callosum was a component of a syndrome in four children. The outcome was not favorable for the majority of patients, even in the first group without significant involvement of other systems. Severe handicaps with developmental delay, intellectual disability, and neurologic deficit were observed in patients with additional telencephalic dysgenesis or syndromic form of corpus callosum agenesis.     

Clinicopathological findings associated with agenesis of the corpus callosum

Seven hundred five cases of agenesis of the corpus callosum (ACC) are reviewed from the literature (n = 660) and from our own observations (n = 45). The diagnosis was made or confirmed using neuroradiological techniques (n = 519) and necropsy or surgery (n = 231). Association with abnormalities often of chromosomes 8, 11, 13-15 and 18 suggests their involvement in abnormal corpus callosum (CC) morphogenesis. Four syndromes (e.g. Aicardi, acrocallosal, Andermann and Shapiro) are characterized by ACC, while others are only sporadically associated (e.g. fetal alcohol syndrome, Dandy-Walker syndrome, Leigh disease, Arnold-Chiari II syndrome). In non-Aicardi patients, the male-to-female ratio was 3:2 and X-linked recessive inheritance is postulated to play a role in some cases. Common abnormalities in acallosal patients included: mental retardation (MR), 73% [corrected]; seizures, 42%; ocular anomalies, 42%; gyral abnormalities, 32%; hydrocephalus, 23%; other central nervous system (CNS) lesions, 29%; costovertebral defects, 24%. Developmental disabilities are not attributable to absence of the CC per se, but due to other CNS malformation or dysfunction, which may be genetic or non-genetic. Future research using recombinant DNA techniques will enable isolation and identification of specific chromosomal defects in those cases with a genetic abnormality.     

Psychosis in Apert''s syndrome with partial agenesis of the corpus callosum.

A 19-year-old male with Apert's syndrome developed psychotic symptoms that responded to haloperidol. He was also found to have partial agenesis of the corpus callosum and enlarged lateral ventricles on a head CT scan. The implications of these findings in the context of psychotic symptoms are discussed. There are no previous reports of psychosis in patients with Apert's syndrome.     

Social cognition in individuals with agenesis of the corpus callosum

Past research has revealed that individuals with agenesis of the corpus callosum (ACC) have deficits in interhemispheric transfer, complex novel problem-solving, and the comprehension of paralinguistic aspects of language. Case studies and family reports also suggest problems in social cognition. The performance of 11 individuals with complete ACC and with normal intelligence was compared to that of 13 IQ- and age-matched controls on three measures of social cognition. Individuals with ACC were indistinguishable from controls on the Happé Theory of Mind Stories and the Adult Faux Pas Test, but performed significantly worse on various portions of the Thames Awareness of Social Inference Test (TASIT) involving interpretations of videotaped social vignettes. Further analysis of the TASIT indicated that individuals with ACC showed deficiency in the recognition of emotion, weakness in understanding paradoxical sarcasm, and particular difficulty interpreting textual versus visual social cues. These results suggest that the tendency for deficient social cognition in individuals with ACC stems from a combination of difficulty integrating information from multiple sources, using paralinguistic cues for emotion, and understanding nonliteral speech. Together, these deficits would contribute to a less robust theory of mind.     

Interhemispheric cysts in association with agenesis of the corpus callosum

Two cases of complete agenesis of the corpus callosum each with large interhemispheric cysts are presented. The first case is an adult patient with chronic renal failure secondary to adult polycystic renal disease who was neurologically asymptomatic until she had a seizure during hemodialysis. The second case is an infant, who was diagnosed in utero as hydrocephalic, with severe mental and motor retardation and intractable seizures. The clinicopathologic findings in the two cases are presented, along with a discussion of the possible etiologies and clinical significance.     

Hallermann-Streiff syndrome associated with complete agenesis of the corpus callosum

Hallermann-Streiff syndrome is a rare clinical entity with unknown etiology characterized by a birdlike face, microphthalmia, a beaked nose, hypotrichosis, and proportional small stature. We present a 4-year-old boy in whom magnetic resonance imaging showed complete agenesis of the corpus callosum, which has not been presented in the literature.     

Familial agenesis of the corpus callosum with hypothermia and apneic spells

Two siblings, a boy and a girl, with agenesis of the corpus callosum, apneic spells, attacks of apnea, cyanosis and spontaneous hypothermia, are reported about. Both children died after a few months of life. Postmortem examination revealed a severe spongiosis of the white matter in addition to the agenesis of the corpus callosum and septum pellucidum, in both cases.     

Alexithymia and somatization in agenesis of the corpus callosum

Deficient communication between the cerebral hemispheres is one of several prevailing neurobiological explanations for alexithymia and has been strongly supported by research on patients with commissurotomy. We examined self-reported symptoms of alexithymia in adults with agenesis of the corpus callosum (AgCC), a condition characterized by more subtle reductions in interhemispheric transfer than in commissurotomy. Sixteen adults with AgCC and full-scale intelligence quotient >80 were compared with 15 neurotypical controls group-matched for age and intelligence score. The AgCC group endorsed greater difficulty identifying and describing feelings and more vague physical symptoms than controls but similar levels of emotional experience and emotional coping. This finding of impaired emotional interpretation with intact emotional experience is consistent with findings in callosotomy patients, implicating the critical role of the corpus callosum in cognitive dimensions of emotion processing. Further study of alexithymia in AgCC using task-based measures may help clarify the nature of this relationship.     

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.     

Congenital oculomotor apraxia with corpus callosum agenesis and subtentorial atrophy

A 7 year-old child with congenital oculomotor apraxia (Cogan's syndrome) presented with mainly voluntary horizontal saccadic movements. Fixation of a visual target could be obtained only by a sudden movement of the head preceded by eyelid blinking. Electro-oculography confirmed the predominant disturbance of saccadic movements (delay in onset, hypometria). CT scan showed agenesis of the corpus callosum and atrophy of the vermis together with enlargement of the 4th ventricle and pre-pontine cisternae. The role of these anomalies in the pathogenesis of this rare congenital syndrome of good prognosis is discussed.     

Partial agenesis of the anterior corpus callosum: correlation between appearance, imaging, and neuropathology

Two patients with partial (semilobar) holotelencephaly are reported with apparent partial agenesis of the corpora callosa. These patients are of interest because they appear to possess the posterior portion of the corpus callosum but not its anterior component. Because the corpus callosum develops in the commissural plate rostrally and is elaborated in a rostral-caudal gradient, this apparent lack of the rostral component is embryologically puzzling. The neuropathologic studies of 1 patient resolved the apparent discrepancy between magnetic resonance imaging and embryology of the corpus callosum. With these data, we addressed the embryologic factors that may explain this malformation.     

Unilateral photoconvulsive response in agenesis of the corpus callosum

An 11-year-old female presented with the unusual coexistence of self-induced photogenic epilepsy and an atypical epileptiform ictal EEG pattern evoked by intermittent photic stimulation. The EEG showed irregular 2.5-4 Hz spike-wave and polyspike-wave complexes, strictly localized on the left hemisphere, and associated with impairment of consciousness and myoclonic jerking of the contralateral side of the body. A computer tomographic scan showed agenesis of the corpus callosum. According to the literature on corpus callosum section in uncontrolled epilepsies, we hypothesize that in our patient the agenesis of the corpus callosum probably prevented the generalization of the ictal EEG pattern evoked by intermittent photic stimulation.