Christianson Syndrome: Spectrum of Neuroimaging Findings

Abstract

Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized by severe intellectual disability, absent speech, microcephaly, ataxia, seizures, and behavioral abnormalities. The clinical phenotypes of CS and Angelman syndrome (AS) are similar. Differentiation between CS and AS is important in terms of genetic counseling. We report on two children with CS and confirmed mutations in SLC9A6 focusing on neuroimaging findings and review the available literature. Cerebellar atrophy (CA) occurs in approximately 60% of the patients with CS and develops after the age of 12 months. Hyperintense signal of the cerebellar cortex (CbC) is less common, and may be diffuse, patchy, or involve only the inferior part of the cerebellum and is best seen on coronal fluid attenuation inversion recovery images. CA and CbC-hyperintensity are not neuroimaging features of AS. In a child with the phenotype of AS, CA and/or CbC-hyperintensity are rather specific for CS and should prioritize sequencing of SLC9A6.

Keywords

Christianson syndrome - neuroimaging - cerebellar atrophy - cerebellar cortex hyperintensity

• References

• 1 Gilfillan GD, Selmer KK, Roxrud I , et al. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet 2008; 82 (4) 1003-1010
• 2 Christianson AL, Stevenson RE, van der Meyden CH , et al. X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet 1999; 36 (10) 759-766
• 3 Schroer RJ, Holden KR, Tarpey PS , et al. Natural history of Christianson syndrome. Am J Med Genet A 2010; 152A (11) 2775-2783
• 4 Tzschach A, Ullmann R, Ahmed A , et al. Christianson syndrome in a patient with an interstitial Xq26.3 deletion. Am J Med Genet A 2011; 155A (11) 2771-2774
• 5 Mignot C, Héron D, Bursztyn J , et al. Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum. Brain Dev 2013; 35 (2) 172-176
• 6 Riess A, Rossier E, Krüger R , et al. Novel SLC9A6 mutations in two families with Christianson syndrome. Clin Genet 2013; 83 (6) 596-597
• 7 Takahashi Y, Hosoki K, Matsushita M , et al. A loss-of-function mutation in the SLC9A6 gene causes X-linked mental retardation resembling Angelman syndrome. Am J Med Genet B Neuropsychiatr Genet 2011; 156B (7) 799-807
• 8 Fichou Y, Bahi-Buisson N, Nectoux J , et al. Mutation in the SLC9A6 gene is not a frequent cause of sporadic Angelman-like syndrome. Eur J Hum Genet 2009; 17 (11) 1378-1380
• 9 Williams CA, Driscoll DJ, Dagli AI. Clinical and genetic aspects of Angelman syndrome. Genet Med 2010; 12 (7) 385-395
• 10 Garbern JY, Neumann M, Trojanowski JQ , et al. A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition. Brain 2010; 133 (Pt 5) 1391-1402
• 11 Poretti A, Wolf NI, Boltshauser E. Differential diagnosis of cerebellar atrophy in childhood. Eur J Paediatr Neurol 2008; 12 (3) 155-167
• 12 Strømme P, Dobrenis K, Sillitoe RV , et al. X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction. Brain 2011; 134 (Pt 11) 3369-3383
• 13 Dagli AI, Williams CA. Angelman syndrome. In: Pagon RA, Adam MP, Bird TD, , et al, eds. GeneReviews. Seattle, WA: University of Washington; 2011
• 14 Edery P, Chabrier S, Ceballos-Picot I, Marie S, Vincent MF, Tardieu M. Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: a report on three patients. Am J Med Genet A 2003; 120A (2) 185-190
• 15 Jurecka A, Zikanova M, Jurkiewicz E, Tylki-Szymańska A. Attenuated adenylosuccinate lyase deficiency: a report of one case and a review of the literature. Neuropediatrics 2013; (epub ahead of print). doi:10.1055/s-0033-1337335
• 16 Poretti A, Boltshauser E. Table 20. Cerebellar cortex hyperintensity. In: Boltshauser E, Schmahmann JD, , eds. Cerebellar Disorders in Children. London, United Kingdom: Mac Keith Press; 2012: 415