Perry syndrome

Alternate names

Parkinsonism with alveolar hypoventilation and mental depression

Definition

A rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression.

Epidemiology

The prevalence is unknown. It has been described in 53 cases from 11 families to date in Canada, U.S., U.K., France, Turkey and Japan.

Cause

Perry syndrome is caused by mutations (five identified to date) in exon 2 of the' dynactin DCTN1 gene' coding for p150glued, the major subunit of the dynactin protein complex.

Gene mutations

• Mutations in this gene alter the binding affinity of dynactin for microtubules and consequently this leads to the impairment of this important transport protein.
• Nigral neurons seem to be more affected by the dysfunction of this protein, explaining their increased cell death and the distinct pathology seen in Perry syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Perry syndrome is inherited in an autosomal dominant manner with full penetrance and children of a parent with the disease have a 50% chance of also having the mutation and developing the disease. Pre-symptomatic diagnosis can be offered to at-risk individuals.

Onset

Perry syndrome has a mean age of onset of 48 years (range 35-61)

Signs and symptoms

• This condition is presents with parkinsonism (akinetic-rigid and rather symmetric), psychiatric changes manifesting as depression, lethargy, withdrawal, apathy, and changes in character, as well as sleep difficulties.
• The usual duration of Perry syndrome is about 5 years, with severe weight loss and central hypoventilation being seen late in the disease course.
• Marked autonomic dysfunction was reported in one family from Japan.
• Patients are often bedridden or wheelchair bound as motor impairment may be severe at a later stage of the disease.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Apathy(Lack of feeling, emotion, interest)
• Central hypoventilation
• Depressivity(Depression)
• Parkinsonism
• Sleep disturbance(Difficulty sleeping)
• Tremor
• Weight loss

5%-29% of people have these symptoms

• Dementia(Dementia, progressive)
• Hypotension(Low blood pressure)
• Personality changes(Personality change)

Diagnosis

• Diagnosis is based on clinical findings of early-onset parkinsonism combined with depression, weight loss and hypoventilation and is confirmed by a molecular genetic test finding a mutation in the DCTN1 gene.
• Major histological findings consist of neuronal loss and TAR DNA-binding protein (TDP-43)-positive pathology in the substantia nigra and locus coeruleus, without Lewy bodies.
• Sleep studies should be performed to detect hypoventilation.

Antenatal diagnosis Antenatal diagnosis is possible in laboratories that offer custom prenatal testing for families with a known DCTN1 mutation.

Treatment

• There is no cure for Perry syndrome.
• Symptomatic treatment requires a multidisciplinary team.
• Dopaminergic therapy is given to patients to help with parkinsonism, usually using levodopa / carbidopa.
• Response to levodopa can be erratic or absent but large doses (>2g) have been successful in reducing symptoms in several patients.
• Patients with hypoventilation require ventilator support (invasive or non-invasive), particularly at night.
• Respiratory function should be monitored continuously.
• Psychiatric follow-up along with antidepressant drugs are needed to manage depression and prevent suicide.
• Weight should be monitored and a high caloric diet should be implemented when weight loss is present.
• With worsening symptoms hospitalization and major medical assistance is often required.

Prognosis

• Perry syndrome progresses rapidly and the prognosis is poor.
• Death is due to respiratory insufficiency or suicide or, in some cases, can be sudden and unexplained.
• Ventilation assistance may prolong survival with an acceptable quality of life.

NIH genetic and rare disease info

• NIH info on Perry syndrome

Perry syndrome is a rare disease.

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