Research: HSP: MAST Syndrome

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A clinical study of Mast syndrome, an autosomal

recessive form of hereditary spastic paraplegia with

dementia. A.H. Crosby1, C. Proukakis1, M. Simpson1,

M.A. Patton1, H. Cross2. 1) Dept Medical Genetics, St

's Hospital Med Sch , London, United Kingdom

SW17 0RE; 2) Dept Ophthalmology, University of Arizona

School of Medicine, 655 N. Alveron Way, Tuscon, USA.

Mast syndrome, originally described in 1967, is an

autosomal recessive complicated form of hereditary

spastic paraplegia (HSP) with dementia present at high

frequency amongst the Old Order Amish. We have studied

14 affected individuals with ages ranging from 31 to

62, with a consequent great variation in disease

severity. Milestones were sometimes delayed, and mild

motor and learning difficulties were often noted in

childhood. Several patients were married and had

children. Decline in walking and mental function

started in early adulthood, although age of onset was

difficult to define. The volume of speech also

declined and swallowing difficulties arose later. The

condition was clearly progressive in all, leading to

akinetic mutism in the most severe. Mini mental test

scores ranged from 0 to 14. All had clear pyramidal

signs which were much more severe in the lower limbs.

Mild cerebellar abnormalities were seen, and the most

advanced cases also had extrapyramidal movements. MRI

scans in 3 patients revealed a thin corpus callosum,

cerebral atrophy and white matter abnormalities. The

Mast syndrome is thus an example of HSP associated

with adult-onset dementia and a thin corpus callosum.

Parallel genetic studies have led to the

identification of a causative mutation in the

polypeptide product of SPG21, designated maspardin

(Mast syndrome, spastic paraplegia, autosomal

recessive with dementia).