Blepharospasm, Benign Essential, Susceptibility To

A number sign (#) is used with this entry because of evidence that susceptibility to benign essential blepharospasm (primary focal dystonia affecting the orbicularis oculi muscles) may be associated with a polymorphic microsatellite marker 5-prime to the dopamine receptor DRD5 gene (126453) on chromosome 4p16.

Description

Blepharospasm is a form of primary focal dystonia affecting the orbicularis oculi muscles, usually beginning in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. In severe cases, this can lead to functional blindness (summary by Misbahuddin et al., 2002).

Clinical Features

Misbahuddin et al. (2002) studied 88 patients with blepharospasm. The male-to-female ratio was 1:4. The mean age at onset was 55.83 years.

Defazio et al. (2011) collected information on 122 consecutive Italian patients with blepharospasm in an outpatient clinic. Screening of 418 first-degree relatives found that 27 relatives from 23 (18.8%) of the families had dystonia, including 16 with focal blepharospasm, 2 with blepharospasm as part of segmental dystonia, 6 with cervical dystonia, and 3 with hand dystonia. There was no difference in age at onset of blepharospasm or tendency to spread between those with a family history (23 probands and 18 relatives) and the 99 probands without a family history. Detailed questionnaire indicated that the presence of ocular symptoms, such as dry eye, blepharitis, or keratoconjunctivitis, was associated with a significant 3.4-year reduction in age at onset, and coffee drinking with a significant 5.7-year later age at onset of blepharospasm. The findings were similar in both familial and sporadic cases, suggesting a common etiology in both forms.

Inheritance

Defazio et al. (2011) stated that blepharospasm is a multifactorial disorder to which environmental and genetic factors contribute.

Molecular Genetics

Misbahuddin et al. (2002) found an association between blepharospasm and allele 2 of a dinucleotide repeat of the DRD5 gene (126453.0001).

Among 100 German and 121 French patients with idiopathic focal dystonia, including blepharospasm and torticollis, Sibbing et al. (2003) found no association with allele 2 or allele 6 of the DRD5 polymorphism.

Animal Model

From studies in a rat model, Schicatano et al. (1997) concluded that a combination of both cell destruction in the substantia nigra pars compacta and a lesion weakening the orbicularis oculi muscle can lead to a condition resembling blepharospasm in humans.