Sir, An 8-year-old girl presented with defective motor coordination, a speech delay, behavioural problems, and generalised hypotonia. On examination, she was found to have hypermobile joints; a cardiac anomaly (patent ductus arteriosus); facial dysmorphism, and irregularly spaced, overcrowded teeth. Magnetic resonance imaging (MRI) of the brain performed as part of the neurologic work-up showed generalised hypodense white matter with multiple widely distributed foci of high signal intensity on the T2 and flair sequences [ ]. On T1 sequences, these areas were hypointense. Subsequent investigations confirmed an underlying rare chromosomal anomaly called tetrasomy X (48, XXXX). Tetrasomy X is a rare chromosomal anomaly that was first reported in 1961 in two children with neuro- disabilities.1–3 Although early case reports suggest mental deficiency as an obligatory feature of the syndrome, more recent reports confirm considerable variability in the phenotypical expression, making it difficult to assess the exact prevalence of the disorder.4 In this 8-year-old girl, the presence of facial dysmorphism, a cardiac anomaly, and central hypotonia prompted the magnetic resonance imaging (MRI) brain scan as well as subsequent investigations that uncovered an otherwise unsuspected underlying disorder. Sultan Qaboos University Med J, November 2012, Vol. 12, Iss. 4, pp. 537-538, Epub. 20th Nov 12 Submitted 24th Dec 11 Revision Req. 18th Apr 12, Revision recd. 25th Apr 12 Accepted 5th Jun 12 تغريات غري عادية يف الدماغ يف حالة شذوذ الرباع x الصبغي م�صيلبواال ، فينوجوباالن Unusual Brain Changes in Tetrasomy X Chromosomal Anomaly M. Mshelbwala1 and *P. Venugopalan2 LETTER TO EDITOR Figure 1: Magnetic resonance imaging of the brain in a child with tetrasomy X showing diffuse ill-defined areas of high density on a T2 weighted image (A) and an axial flare image (B). The corresponding areas were more lucent on the T1 weighted images. Unusual Brain Changes in Tetrasomy X Chromosomal Anomaly 538 | SQU Medical Journal, November 2012, Volume 12, Issue 4 MRI changes associated with sex chromosome aneuploidies were extensively reviewed in a recent Australian publication.5 Reported studies mostly involve children with Klinefelter’s syndrome (47, XXY), and 47, XXY males. Findings in 47, XXY males include decreased grey and white matter volumes, with most pronounced effects in the frontal and temporal lobes. Functional studies have shown evidence of decreased lateralisation. It is widely believed that the severity of brain changes increases with the number of X chromosomes, as shown in children with Klinefelter’s syndrome and varying numbers of X chromosomes. A report on 3 children with 49, XXXXY documented varying degrees of brain volume loss and white matter changes, and similar changes could be expected with 48, XXXX.2 However, our patient exhibited widespread focal increase in the cerebral white matter density, with a normal cerebellum and brain stem. Although the exact relationship between the brain changes and neurobehavioural manifestations has not been elucidated, these changes are consistent with developmental aberrations, and could form the basis for the above manifestations in affected children.5 M. Mshelbwala1 and *P. Venugopalan2 1Department of Paediatrics, University Hospitals of North Tees & Hartlepool, Holdforth Road, Hartlepool, UK 2Department of Child Health, Brighton & Sussex University Hospitals, Brighton, UK *Corresponding Author e-mail: pvenugopalan@gmail.com References 1. Schoubben E, Decaestecker K, Quaegebeur K, Danneels L, Mortier G, Cornette L. Tetrasomy and pentasomy of the X chromosome. Eur J Pediatr 2011; 170:1325–7. 2. Hoffman TL, Vossough A, Ficicioglu C, Visootsak J. Brain magnetic resonance imaging findings in 49, XXXXY syndrome. Pediatr Neurol 2008; 38:450–3. 3. Carr D, Barr ML, Plunkett ER. An XXXX sex chromosome complex in two mentally defective females. Canad Med Ass J 1961; 84:131–7. 4. Blackston RD, Chen ATL. A case of 48, XXXX female with normal intelligence. J Med Genet 1972; 9:230–2. 5. Lenroot RK, Lee NR, Giedd JN. Effects of sex chromosome aneuploidies on brain development: Evidence from neuroimaging studies. Dev Disabil Res Rev 2009; 15:318–27.