The prevalence of "pure" autosomal dominant hereditary spastic paraparesis in the island of Ireland. (Paper).

Objectives: Hereditary spastic paraparesis (HSP) is clinically and genetically heterogeneous. "Pure" autosomal dominant (AD) HSP is most common and eight genetic loci are identified to date. Previous studies have included autosomal recessive and sporadic cases in prevalence calculations. This study aimed to determine the prevalence and features of pure ADHSP in the island of Ireland.

Methods: Index cases were identified from a 5 year survey of all adult and paediatric neurologists, clinical geneticists, hospital records, and hospital inpatient enquiry system data in Ireland, north and south. Families were examined by two neurologists and classified as affected or unaffected according to specific criteria. The prevalence date was set at 1 June 2000 and the midyear population estimate for the previous year was 5.436 million.

Results: Eighty two patients with pure ADHSP and a further 12 obligate carriers from 19 families were identified. In total 69 patients with pure ADHSP were alive and resident in Ireland at the prevalence date. Twenty nine per cent of these were asymptomatic but with signs of paraparesis.

Conclusions: The prevalence of ADHSP in Ireland to estimated to be 1.27/100 000 population. The high proportion of asymptomatic cases and obligate carriers means that this condition is likely to be underdiagnosed.

Hereditary spastic paraparesis (HSP) comprises a group of inherited neurodegenerative disorders with the shared characteristic of slowly progressive spasticity weakness of the legs. It is subdivided into "pure" or "complicated" forms depending on whether the paraparesis exists in isolation or with other major clinical features. (1 2) Genetic heterogeneity is marked and autosomal dominant (AD), autosomal recessive (AR), and X blinked inheritance is described for both pure and complicated forms. (3) To date 16 genetic loci have been identified for all types of HSP. (4-9) The most common form of HSP is pure ADHSP and even this is heterogeneous with eight loci identified. The most common cause of pure ADHSP, accounting for up to 40% of cases is a mutation in the SPAST gene on chromosome 2p. (10)

The prevalence of HSP varies with different studies. Before Harding in 1983, the distinction between pure and complicated forms changed from study to study and prevalence rates varied consequently. Since then, reports have tended to include autosomal recessive forms and sporadic cases in their calculations. To date there has been no study looking at pure ADHSP alone. The aim of our study therefore was to examine the prevalence of all cases of pure ADHSP in the island of Ireland as this represents the most homogeneous group within the disorder.

METHODS

Study area

The island covers an area of 84 433 [km.sup.2] and comprises the Republic of Ireland and Northern Ireland, which is part of the United Kingdom. In 1999, the midyear estimate of the population was 3.7447 million for the Republic of Ireland and 1.6918 million for Northern Ireland giving 5.436 million in total. (11) The latest year in which population estimates are available for Northern Ireland is 1999 and the eight regional authorities in the Republic of Ireland and regional rates are compared on this basis.

Case ascertainment

We undertook a prospective, population based study of HSP in Ireland over 5 years from July 1995 to 1 July 2000. Index cases, identifying potential HSP pedigrees, were identified from four sources; (1) adult and paediatric neurologists; (2) clinical geneticists; (3) review of hospital records of four major neurological centres in Ireland and (4) the Hospital Inpatient enquiry system (HIPE).

All index cases were seen and examined by two neurologists …