Case reportCranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome
Introduction
Hallervorden-Spatz syndrome (MIM# 234200) is a childhood-onset neurodegenerative disorder associated with brain iron accumulation [1], [2]. The diagnosis in a child with neurologic changes usually is first suspected after cranial magnetic resonance imaging (MRI), which reveals an area of hypointensity in the globus pallidus with a central region of hyperintensity on T2-weighted images, the so-called eye-of-the-tiger sign [3], [4], [5], [6]. This report describes two families, each with an affected child, in which a sibling revealed presymptomatic cranial MRI changes characteristic of the disease.
Section snippets
Case reports
In both families the parents requested that their other children be evaluated for Hallervorden-Spatz syndrome. Each child was examined by the pediatric neurologist who had diagnosed the affected sibling, and all children underwent cranial MRI, except Patient 7. Linkage analysis was performed on DNA samples from members of each family with markers near the gene locus for Hallervorden-Spatz syndrome, called NBIA1, on chromosome 20p13 [7]. Pedigrees are illustrated in Figure 1.
Discussion
In two families with Hallervorden-Spatz syndrome, we have diagnosed a child on the basis of characteristic cranial MRI changes and shared haplotypes with affected siblings before their developing clinical signs or symptoms. At the time of diagnosis of the proband in each family, the parents requested that all siblings be evaluated for Hallervorden-Spatz syndrome. Clinical, radiographic, and genetic studies of the siblings were conducted. In each sibship, one unaffected child was ascertained.
Acknowledgements
The authors thank the families with Hallervorden-Spatz syndrome, without whom this study could not have been performed. A. Malone and S. Bae provided valuable technical assistance. This work was supported in part by NIH grants 1R01 EY12353 and 5K23 EY00348 to SJH.
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