Indian J Pediatr DOI 10.1007/s12098-013-1333-z
PICTURE OF THE MONTH
Lissencephaly with Subcortical Band Heterotopia in an Indian Family Puneet Jain & Dhulika Dhingra & Atin Kumar & Suvasini Sharma & Jagdish Chandra & Satinder Aneja
Received: 15 November 2013 / Accepted: 27 December 2013 # Dr. K C Chaudhuri Foundation 2014
An 11-y-old girl presented with seizures for the last 12 mo. She had no adverse perinatal events with normal development history. She had six episodes of generalized-tonicclonic seizures in the last 12 mo. There were no other seizure types. She had received gradually increasing doses of valproate with partial response. She was a student of class five with poor school performance. The systemic examination was unremarkable besides mild intellectual disability. Her EEG showed multifocal epileptiform abnormalities. Her younger brother was 18-mo-old. He had global developmental delay, one episode of seizure at 6 mo of age, microcephaly and spasticity. There was no other significant family
P. Jain (*) : S. Sharma : S. Aneja Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, India e-mail: [email protected] D. Dhingra : J. Chandra Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India A. Kumar Department of Radio-diagnosis, JPN Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
history and their parents were non-consanguineous. His EEG showed generalized high amplitude alpha-frequency activity intermingled with beta activity, characteristic of lissencephaly. The neuroimaging of the two siblings is shown in Figs. 1 and 2. Their anti-convulsant drugs were optimized along with the supportive care. Genetic counseling was done. However, they refused for the genetic testing. Lissencephaly and subcortical band heterotopias are classic malformations associated with abnormal neuronal migration [1]. Lissencephaly is characterized by smooth cerebral surface with abnormally thick cortex. Subcortical band heterotopias, also known as ‘double cortex’, consist of normal cortex, a thin zone of white matter underlying the cortex, and then a zone of heterotopic neurons. Lissencephaly and subcortical band heterotopias lie on a single malformation spectrum [2]. The mutations of the DCX gene are known to cause lissencephaly in males and subcortical band heterotopia in females in rare reported cases [3]. The patients with classical lissencephaly have severe psychomotor retardation with epilepsy. However, patients with subcortical band heterotopias may have a milder course. They may have mild to moderate intellectual disability with usually late onset epilepsy. The severity and gradient of lissencephaly and the associated callosal and cerebellar defects may guide the genetic testing of such patients [3].
Indian J Pediatr Fig. 1 Axial T1 (a) and T2 (b) weighted MR axial images of the brain of the older girl show a linear area of grey matter isointense to grey matter on both T1 and T2 weighted images in subcortical location of cerebral hemispheres consistent with subcortical band heterotopia
Fig. 2 Axial T1 (a) and T2 (b) weighted MR axial images of the brain of her younger brother show smooth appearance of cortical grey matter bilaterally with increased thickness consistent with lissencephaly. Note the indentation from the sylvian fissures
Acknowledgments The authors are grateful to Dr Nadia Bahi-Buisson (Paris, France) for offering free genetic testing for DCX for the reported family. Contributions PJ, DD and SS: Provided the clinical care to the patient under the supervision of SA and JC; AK: Provided the radiological inputs; PJ: Drafted the manuscript which was read and approved by all the authors. SA will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: Update 2012. Brain. 2012;135:1348–69. 2. Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, et al. Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. Hum Mol Genet. 1999;8:1757–60. 3. Dobyns WB. The clinical patterns and molecular genetics of lissencephaly and subcortical band heterotopia. Epilepsia. 2010;51: S5–9.
PICTURE OF THE MONTH
Lissencephaly with Subcortical Band Heterotopia in an Indian Family Puneet Jain & Dhulika Dhingra & Atin Kumar & Suvasini Sharma & Jagdish Chandra & Satinder Aneja
Received: 15 November 2013 / Accepted: 27 December 2013 # Dr. K C Chaudhuri Foundation 2014
An 11-y-old girl presented with seizures for the last 12 mo. She had no adverse perinatal events with normal development history. She had six episodes of generalized-tonicclonic seizures in the last 12 mo. There were no other seizure types. She had received gradually increasing doses of valproate with partial response. She was a student of class five with poor school performance. The systemic examination was unremarkable besides mild intellectual disability. Her EEG showed multifocal epileptiform abnormalities. Her younger brother was 18-mo-old. He had global developmental delay, one episode of seizure at 6 mo of age, microcephaly and spasticity. There was no other significant family
P. Jain (*) : S. Sharma : S. Aneja Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, India e-mail: [email protected] D. Dhingra : J. Chandra Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India A. Kumar Department of Radio-diagnosis, JPN Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
history and their parents were non-consanguineous. His EEG showed generalized high amplitude alpha-frequency activity intermingled with beta activity, characteristic of lissencephaly. The neuroimaging of the two siblings is shown in Figs. 1 and 2. Their anti-convulsant drugs were optimized along with the supportive care. Genetic counseling was done. However, they refused for the genetic testing. Lissencephaly and subcortical band heterotopias are classic malformations associated with abnormal neuronal migration [1]. Lissencephaly is characterized by smooth cerebral surface with abnormally thick cortex. Subcortical band heterotopias, also known as ‘double cortex’, consist of normal cortex, a thin zone of white matter underlying the cortex, and then a zone of heterotopic neurons. Lissencephaly and subcortical band heterotopias lie on a single malformation spectrum [2]. The mutations of the DCX gene are known to cause lissencephaly in males and subcortical band heterotopia in females in rare reported cases [3]. The patients with classical lissencephaly have severe psychomotor retardation with epilepsy. However, patients with subcortical band heterotopias may have a milder course. They may have mild to moderate intellectual disability with usually late onset epilepsy. The severity and gradient of lissencephaly and the associated callosal and cerebellar defects may guide the genetic testing of such patients [3].
Indian J Pediatr Fig. 1 Axial T1 (a) and T2 (b) weighted MR axial images of the brain of the older girl show a linear area of grey matter isointense to grey matter on both T1 and T2 weighted images in subcortical location of cerebral hemispheres consistent with subcortical band heterotopia
Fig. 2 Axial T1 (a) and T2 (b) weighted MR axial images of the brain of her younger brother show smooth appearance of cortical grey matter bilaterally with increased thickness consistent with lissencephaly. Note the indentation from the sylvian fissures
Acknowledgments The authors are grateful to Dr Nadia Bahi-Buisson (Paris, France) for offering free genetic testing for DCX for the reported family. Contributions PJ, DD and SS: Provided the clinical care to the patient under the supervision of SA and JC; AK: Provided the radiological inputs; PJ: Drafted the manuscript which was read and approved by all the authors. SA will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: Update 2012. Brain. 2012;135:1348–69. 2. Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, et al. Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. Hum Mol Genet. 1999;8:1757–60. 3. Dobyns WB. The clinical patterns and molecular genetics of lissencephaly and subcortical band heterotopia. Epilepsia. 2010;51: S5–9.
