Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP)

Abstract

Sex linked dystonia parkinsonism (XDP), also referred to as "lubag" in American literature, was described in 1975 occurring endemically in Panay, Philippines. It is an adult onset, sex linked, predominantly male, severe, progressive movement disorder with high penetrance and a high frequency of generalisation. The movement disorder is characterised by dystonic movements, usually starting in the 3rd or 4th decade, spreading to generalisation within two to five years. The dystonia coexists or is replaced by parkinsonism usually beyond the 10th year of illness. No treatment has been found to be effective. Neuroimaging shows caudate and putamenal atrophy in patients reaching the parkinsonian stage. Neuropathology reveals pronounced atrophy of the caudate and putamen, mostly in the cases with long standing illness. The sex linked pattern of inheritance has been established. Genetic studies have located the affected gene (DYT3) to Xq13.1, with one group mapping the XDP gene to a < 350 kb locus in the DXS 7117-DXS 559 region.

Figure 1

(A) Three brothers with X linked dystonia parkinsonism (XDP) in varying stages. Patient on the left: 57 years old, after 22 years of illness, with remaining dystonia and early parkinsonism. Patient in the middle: 67 years old, after 21 years of illness, parkinsonian showing masked facies and lid retraction. Patient on the right: 53 years old , after 13 years of illness, generalised dystonia, oromandibular and leg dystonia, starting bradykinesia. (B) Generalised XDP, seventh year of illness, severe generalised dystonia with trunk extension. (C) XDP at eigth year of illness, severe generalised dystonia with trunk flexion.

Figure 2

T2 weighted (T2W), T1W, and infrared (IR) images demonstrate mild caudate atrophy and mild putaminal atrophy with peripheral high signal rim on TW2 images. Clinically, the patient has dystonia but no parkinsonism.

Figure 3

T2 weighted (T2W), FLAIR (fluid attenuated inversion recovery), and T1W images demonstrate severe head atrophy with ex vacuo dilatation of the frontal horns and severe atrophy of the putamina with “slit-like” high signal intensity on T2W and low signal intensity on T1W. Clinically, this patient has both dystonia and parkinsonism.

Figure 4

Caudate atrophy. Note the linear, rather than the normal convex outline of the caudate in relation to the lateral ventricle.

Figure 5

Neuronal loss and astroliosis of the putamen in X linked dystonia parkinsonism. (A) Haematoxylin and eosin stain. (B) Glial fibrillary acidic protein stain.

Figure 6

Pedigree of family 38 (as of year 2000).

Figure 7

Tracking down the X linked dystonia parkinsonism (XPD) gene.