Objective: Describe a case of dystonia and intracranial calcifications associated with a deletion within 8p11.21

Background: Multiple genes located within chromosome 8p11.21 are associated with movement disorders including SLC20A2 and THAP1. The SLC20A2 gene encodes for an inorganic phosphate transporter within the type III sodium-dependent phosphate transporter family type III sodium-dependent phosphate transporter family, and is associated with idiopathic basal ganglia calcification (or Fahr Syndrome) and can present with parkinsonism, dystonia, tremor, and chorea. THAP1, associated with DYT6, is an autosomal dominant disorder with dystonia typically affecting the craniocervical area and limbs. A deletion including SLC20A2 and THAP1 presenting with a dystonia-plus syndrome has previously been reported in a French Canadian family. In this report, we describe a child with a deletion involving both of these genes who presented with intracranial calcifications and dystonia.

Methods: Case report and review of the literature

Results: The subject was born full term and early development was normal. Subtle motor concerns involving fine motor skills especially in the left hand were noted at the age of 5 years. Function remained relatively stable until age 8 when he had an acute deterioration of gait and motor function.  Involuntary movements included arm posturing with wrist and elbow flexion, worse on the left than the right. Other findings included dysarthria, involuntary head turning, and occasional right shoulder elevation. An initial head CT showed subcortical and basal ganglia calcifications. Metabolic studies were unrevealing and a lumbar puncture was normal. Additional neuroimaging has not shown any progression of calcifications.  Whole exome sequencing was not diagnostic, however, a subsequent SNP array revealed a 628 kB deletion within chromosome 8p11.21 that encompasses SLC20A2 and THAP1. The subject’s father also has intracranial calcifications identified on a head CT obtained following a head injury.

Conclusions: This case describes the childhood onset of brain calcifications and dystonia associated with a deletion involving SLC20A2 and THAP1. This report also emphasizes the potential diagnostic value of a SNP array in individuals with undiagnosed genetic movement disorders

References: Baker M, Strongosky AJ et al., SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia. Neurogenetics (2014) 15:23–30.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intracranial-calcifications-and-dystonia-associated-with-a-novel-deletion-encompassing-slc20a2-and-thap1/