MIAMI—When evaluating a patient with a movement disorder that
seems to be rare, neurologists should employ their clinical expertise and consider
a broad range of possible causes, said Anthony E. Lang, MD, Professor and Director
of Neurology at the University of Toronto.
“Not everything is going to be diag-
nosed with whole exome sequencing,” Dr.
Lang said at the First Pan American Par-
kinson’s Disease and Movement Disorders
Congress. “Think much more broadly than
that, or you are going to miss some important diagnoses
and, in some cases, miss quite treatable diagnoses.”
A patient’s history, the physical and neurologic exam,
and laboratory and genetic testing are important tools
in developing a differential diagnosis. Once a diagnosis
has been made, certain disorders may entail a risk of
long-term complications that require preventive mea-
sures and surveillance.
Dr. Lang cochairs an annual session at the International Congress of Parkinson’s Disease and Movement
Disorders that features video presentations of unusual
cases. “The more you are aware of and the more you
have seen, the more you may have an impact on helping
the patient,” he said.
Approximately 80% of rare diseases are genetic, and
modern molecular genetic tests increasingly allow neurologists to make accurate diagnoses. Other causes of
rare movement disorders include autoimmune disease,
infection, neoplasms, environmental exposures, degenerative disorders, and deficiency states.
Camilo Toro, MD, a neurologist with the NIH Un-
diagnosed Diseases Program, advises that the classical
phenotypes of rare diseases often represent the worst-
case scenario, Dr. Lang said. Neurologists increasingly
are recognizing broader phenotypic variability and
milder forms of rare genetic diseases. In addition, the
boundaries between pediatric and adult
genetic disorders are blurred, and a patient
with more than one genetic disorder may
have a blended phenotype. It is also pos-
sible that a patient has a rare presentation
of a common disorder.
Patient and Family History
Neurologists should consider how a movement disorder began (eg, triggers or precipitants) and whether a patient has other
neurologic or general medical illnesses. A patient’s old
images, videos, and laboratory tests may offer insights.
Genetic counselors can be a valuable resource for neurologists who are interested in learning how to take a
careful family history.
Possible sources of confusion about the inheritance
of genetic disorders include de novo mutations, missed
family history of a disorder (eg, if a relative has a mild
manifestation), incomplete penetrance of dominant
disorders, incorrect attribution of paternity, and the
possibility of pseudodominance in inbred families with
recessive disorders. Other types of inheritance include
maternal inheritance, maternal imprinting (eg, in myoclonus dystonia), and uniparental disomy.
General and Neurologic Examinations
A patient’s habitus, stature, and facial dysmorphism may
be informative. After seeing a patient with Woodhouse-
Sakati syndrome in a case that had been presented at a
conference, Dr. Lang recognized that he had a patient
with the same facial characteristics. “Sure enough, the
patient has Woodhouse-Sakati syndrome,” he said.
Patients with 22q11.2 deletion syndrome may have
variable craniofacial features, and Dr. Lang’s clinic is fol-
lowing a number of patients with parkinsonism or other
movement disorders as a consequence of this disorder.
Skin and related features, including telangiectasia,
pigmentation, and nails, may suggest a diagnosis (eg,
How to Diagnose and Treat
Rare Movement Disorders
Think broadly, take a careful history, and use laboratory tests intelligently.
Anthony E. Lang, MD