Indian J Pediatr DOI 10.1007/s12098-015-1740-4
SCIENTIFIC LETTER
Williams Syndrome with Infantile Spasms İpek Polat & Pakize Karaoglu & Muge Ayanoglu & Uluc Yis & Semra Hiz
Received: 6 November 2014 / Accepted: 2 March 2015 # Dr. K C Chaudhuri Foundation 2015
To the Editor : A 7-mo-old girl was admitted with 1 mo history of symmetric extensor type of jerks in clusters followed by stiffening just after waking up. After the start of sudden jerks, psychomotor development got arrested. She was born at 38 wk of gestation by spontaneous vaginal delivery with a birth weight of 2400 g. She was the first child of healthy nonconsanguineous parents. In the newborn period she was diagnosed with supravalvular aorta stenosis with mild pulmonary stenosis. Her head circumference was 43 cm (50–75p). On physical examination dysmorphic facial features including elfin face, puffy eyes, full cheeks, flat midface, epicanthal folds and long philtrum was noted. Complete blood cell count, biochemical and metabolic tests were normal. Cranial magnetic resonance imaging showed normal findings except thin splenium of corpus callosum. Interictal sleep electroencephalography revealed hypsarrhythmia pattern. She was treated with adrenocorticotropic hormone. She was seizure free after the third dose. Control electroencephalography showed bilateral parietal and occipital epileptic discharges. Despite she was seizure free after the third dose of ACTH, due to the ongoing EEG abnormalities, levetiracetam treatment was continued. Fluorescent in situ hybridization study revealed deletion of 7q11.23 region. She was diagnosed with Williams syndrome. After the cessation of spasms, her psychomotor development also improved. Williams syndrome is a contiguous gene deletion syndrome resulting from the submicroscopic deletion on chromosome 7q11.23 [1]. It is characterized by stenosis of large vessels (supravalvular aorta stenosis with or without pulmonar stenosis), elfin face, dental abnormalities, growth retardation and hypercalcemia during infancy [1, 2]. The central nervous İ. Polat (*) : P. Karaoglu : M. Ayanoglu : U. Yis : S. Hiz Department of Pediatric Neurology, Dokuz Eylul University Hospital, Mithatpasa Cad., Narlidere 35320, Izmir, Turkey e-mail: [email protected]
system features of Williams syndrome include motor and mental retardation with behavioral disorders [2–4]. Seizures, especially infantile spasms are not specific features of Williams syndrome. There are few cases of Williams syndrome with seizures including apnea which correlates with ictal activity on EEG and tonic clonic seizures in a patient with larger deletions towards to the telomere [3–5]. 7q11.23-21.11 region is distal to the specific deletion region (7q11.23) of Williams syndrome. This 7q11.23-21.11 region includes a part or whole of the MAGI2 (Membrane Associated Guanylate Kinase, WW And PDZ Domain Containing 2) gene which is found to be associated with infantile spasms in patients with Williams syndrome [1, 3]. There are also two cases with Williams syndrome and infantile spasms that only have microscopic interstitial deletion without deletion in MAGI2 gene [2, 6]. We could not test whether MAGI2 gene was involved in our case. In conclusion, cases with Williams syndrome should be carefully followed up for the development of infantile spasms which can deteriorate pre-existing neurologic conditions. Conflict of Interest None. Source of Funding None.
References 1. Mizugishi K, Yamanaka K, Kuwajima K, Kondo I. Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms. J Hum Genet. 1998;43:178–81. 2. Morimoto M, An B, Ogami A, et al. Infantile spasms in a patient with Williams syndrome and craniosynostosis. Epilepsia. 2003;44:1459–62.
Indian J Pediatr 3. Marshall CR, Young EJ, Pani AM, et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11. Am J Hum Genet. 2008;83:106–11. 4. Fusco C, Micale L, Augello B, et al. Smaller and larger deletion of Williams-Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits. Eur J Hum Genet. 2014;22:64–70.
5. Myers KA, McLeod R, Bello-Espinosa L. Infantile ictal apneas in a child with Williams-Beuren syndrome. Pediatr Neurol. 2013;48:149–51. 6. Rothlisberger B, Hoigne I, Huber AR, Brunschwiler W, Mori AC. Deletion of 7q11.21-q11.23 and ınfantile spasms without deletion of MAGI2. Am J Med Genet. 2010;152A:434–7.
SCIENTIFIC LETTER
Williams Syndrome with Infantile Spasms İpek Polat & Pakize Karaoglu & Muge Ayanoglu & Uluc Yis & Semra Hiz
Received: 6 November 2014 / Accepted: 2 March 2015 # Dr. K C Chaudhuri Foundation 2015
To the Editor : A 7-mo-old girl was admitted with 1 mo history of symmetric extensor type of jerks in clusters followed by stiffening just after waking up. After the start of sudden jerks, psychomotor development got arrested. She was born at 38 wk of gestation by spontaneous vaginal delivery with a birth weight of 2400 g. She was the first child of healthy nonconsanguineous parents. In the newborn period she was diagnosed with supravalvular aorta stenosis with mild pulmonary stenosis. Her head circumference was 43 cm (50–75p). On physical examination dysmorphic facial features including elfin face, puffy eyes, full cheeks, flat midface, epicanthal folds and long philtrum was noted. Complete blood cell count, biochemical and metabolic tests were normal. Cranial magnetic resonance imaging showed normal findings except thin splenium of corpus callosum. Interictal sleep electroencephalography revealed hypsarrhythmia pattern. She was treated with adrenocorticotropic hormone. She was seizure free after the third dose. Control electroencephalography showed bilateral parietal and occipital epileptic discharges. Despite she was seizure free after the third dose of ACTH, due to the ongoing EEG abnormalities, levetiracetam treatment was continued. Fluorescent in situ hybridization study revealed deletion of 7q11.23 region. She was diagnosed with Williams syndrome. After the cessation of spasms, her psychomotor development also improved. Williams syndrome is a contiguous gene deletion syndrome resulting from the submicroscopic deletion on chromosome 7q11.23 [1]. It is characterized by stenosis of large vessels (supravalvular aorta stenosis with or without pulmonar stenosis), elfin face, dental abnormalities, growth retardation and hypercalcemia during infancy [1, 2]. The central nervous İ. Polat (*) : P. Karaoglu : M. Ayanoglu : U. Yis : S. Hiz Department of Pediatric Neurology, Dokuz Eylul University Hospital, Mithatpasa Cad., Narlidere 35320, Izmir, Turkey e-mail: [email protected]
system features of Williams syndrome include motor and mental retardation with behavioral disorders [2–4]. Seizures, especially infantile spasms are not specific features of Williams syndrome. There are few cases of Williams syndrome with seizures including apnea which correlates with ictal activity on EEG and tonic clonic seizures in a patient with larger deletions towards to the telomere [3–5]. 7q11.23-21.11 region is distal to the specific deletion region (7q11.23) of Williams syndrome. This 7q11.23-21.11 region includes a part or whole of the MAGI2 (Membrane Associated Guanylate Kinase, WW And PDZ Domain Containing 2) gene which is found to be associated with infantile spasms in patients with Williams syndrome [1, 3]. There are also two cases with Williams syndrome and infantile spasms that only have microscopic interstitial deletion without deletion in MAGI2 gene [2, 6]. We could not test whether MAGI2 gene was involved in our case. In conclusion, cases with Williams syndrome should be carefully followed up for the development of infantile spasms which can deteriorate pre-existing neurologic conditions. Conflict of Interest None. Source of Funding None.
References 1. Mizugishi K, Yamanaka K, Kuwajima K, Kondo I. Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms. J Hum Genet. 1998;43:178–81. 2. Morimoto M, An B, Ogami A, et al. Infantile spasms in a patient with Williams syndrome and craniosynostosis. Epilepsia. 2003;44:1459–62.
Indian J Pediatr 3. Marshall CR, Young EJ, Pani AM, et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11. Am J Hum Genet. 2008;83:106–11. 4. Fusco C, Micale L, Augello B, et al. Smaller and larger deletion of Williams-Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits. Eur J Hum Genet. 2014;22:64–70.
5. Myers KA, McLeod R, Bello-Espinosa L. Infantile ictal apneas in a child with Williams-Beuren syndrome. Pediatr Neurol. 2013;48:149–51. 6. Rothlisberger B, Hoigne I, Huber AR, Brunschwiler W, Mori AC. Deletion of 7q11.21-q11.23 and ınfantile spasms without deletion of MAGI2. Am J Med Genet. 2010;152A:434–7.
