The Center for Cerebellar Malformations
Recommendations for Evaluation and Monitoring of Patients with
Joubert Syndrome and Related Disorders
Dear Healthcare Professional,
Joubert Syndrome and Related
Disorders are a group of developmental brain disorders characterized clinically
by disturbances of breathing rhythm, ataxia, oculomotor abnormalities,
developmental delays, and hypotonia.
These disorders are characterized on brain imaging by cerebellar vermis
hypoplasia and the molar-tooth sign of the brainstem. From our review of clinical records from patients in the
Joubert Syndrome Foundation, we have found many with co-existing medical
conditions at a frequency sufficient to warrant a set of guidelines for the
evaluation and monitoring of all patients with Joubert Syndrome and Related
Disorders. These evaluations are
necessary for two reasons. First
is for proper diagnosis of the child, as we find that approximately 20% of
patients display features indicating a subtype of Joubert syndrome or a related
syndrome. Second is to try to
prevent medical complications from these associated conditions, which through
proper screening might be avoided. However, because our total knowledge of
Joubert syndrome and its complications are limited, our recommendations will
need to be evaluated and changed as new information becomes available.
Patients
with Joubert Syndrome and Related Disorders, in addition to the features
mentioned above, have displayed the following features:
1. Abnormal electroretinogram, indicating co-existent
retinal dysplasia and visual impairment.
2. Optic colobomas, which may also limit vision.
3. Kidney disease, which may include juvenile
nephronophthisis or cystic dysplastic kidneys. In some patients, the kidney disease has progressed to
end-stage renal failure that required dialysis or transplantation.
4. Liver fibrosis with or without compromised liver
function.
5. Tongue tumors (hamartomas), enlarged tongues, multiple
frenulae or other unusual
anomalies of the mouth.
6. Polydactyly of fingers or toes that may be simple or
complex.
7. Hypothalamic disorders, sometimes related to a
hypothalamic hamartoma.
8. Additional subtle variation in the appearance of brain
structures, including polymicrogyria or encephalocele.
Because
of these findings, we recommend the following evaluations for patients with
Joubert Syndrome and Related Disorders.
Diagnostic
Evaluations (Initial)
1. Careful physical examination to look specifically for
these co-existent features.
2. Pediatric neurological evaluation for careful
assessment of development and cerebellar function.
3. Medical genetics evaluation with attention focused on
genealogy, growth, polydactyly, micro/macrocephaly, facial dysmorphism, clefts,
lingual nodules, genitalia, and other anomalies.
4. Evaluation of oromotor function by a trained
occupational or speech therapist
5. Brain MRI with axial, coronal, sagittal images
(ideally with 3 mm axial planes through midbrain and pons) and review of the
images by one of the Medical Advisors of the Joubert Syndrome Foundation.
6. Developmental assessment using the Bayley Scale for
children less than 3 years and specific age-appropriate motor/speech/language
testing for older children.
7. Sleep history with attention to apnea/hyperpnea. Polysomnogram in all children diagnosed
under the age of 1. After the age
of 1, this test may be useful if the child has symptoms of sleep apnea.
8. Baseline pediatric ophthalmologic dilated eye exam to
test for retinal dysplasia and coloboma. If visual problems are suspected, a
visual evoked potential (VEP) study may be a useful test that does not require
sedation and can be performed as early as 6 months of age.
9. Baseline electroretinogram (ERG) if possible. Ideally,
this should be done between the ages of 8 months and 3 years, when the sedation
required is minimal.
10. Specific ocular motility examination (with
electrooculogram in older children).
11. Abdominal ultrasound scan with attention to kidneys
and liver.
12. Renal evaluation: Blood urea nitrogen (BUN),
creatinine, complete blood count (CBC), and first-morning void urinalysis with
specific gravity for concentrating ability. A baseline blood pressure should be
obtained.
13. Liver function tests (LFTs) to include transaminases,
albumin and bilirubin.
14. High resolution karyotype.
15. Referral of the child to one of the Medical Advisors
of the Joubert Syndrome Foundation to discuss results of testing or for
questions.
Annual
Evaluations (Yearly)
1. Annual pediatric and neurological evaluation to
monitor systemic or motor abnormalities.
2. Patients may have progressive kidney failure with the
first manifestation being reduced urine concentrating ability or anemia. Therefore, annual abdominal
ultrasounds, BUN, creatinine, CBC, first-morning void urinalysis, and blood
pressure measurements, are recommended until at least age 20 years.
3. Ophthalmologic abnormalities may be progressive. Therefore, annual ophthalmologic
evaluation of retina is recommended with follow-up ERG if indicated by the
ophthalmologist.
4. Annually monitor growth and sexual maturation with
endocrinologic evaluation if indicated
5. Neuropsychological evaluation when patient is able to
cooperate with testing.
6. Periodic developmental assessments as appropriate.
7. Liver evaluation by annual ultrasound (as for kidneys)
and liver function tests.
8. Patients may have problems with swallowing from large
tongues, thus need ongoing evaluation for oromotor function and symptoms of
obstructive apnea.
These
are guidelines only. Individual
patients may have unique needs and management may need to be
individualized. If you have any
questions about Joubert Syndrome and Related Disorders, the Joubert Syndrome
Foundation, or other matters, please do not hesitate to contact one of us.
Sincerely,
Dr.
Joseph G. Gleeson
Dr.
Melissa A. Parisi
Dr.
Bernard L. Maria
Dr.
William B. Dobyns
Medical
Advisors of the Joubert Syndrome Foundation
Contact
information:
Joseph
G. Gleeson, M.D.
Division
of Pediatric Neurology
Department
of Neurosciences
University
of California, San Diego
Childrens
Hospital, San Diego
9500
Gilman Drive
La
Jolla, CA 92093-0624
Ph:
858-822-3786 Fax: 858-534-1437
Melissa
A. Parisi, M.D., Ph.D.
Division
of Genetics and Development, 4H-4
Childrens
Hospital and Regional Medical Center
4800
Sand Point Way, NE
Seattle,
WA 98105
Ph:
206-987-2056 Fax 206-987-2495
mparisi@u.washington.edu
Bernard
L. Maria, M.D., M.B.A.
Chair
of Child Health
University
of Missouri Health Care
One
Hospital Drive
Columbia
MO 65212
Ph:
573-822-6882 Fax: 573-844-5179
William
B. Dobyns, MD
Department
of Human Genetics
The
University of Chicago
Room
319 CLSC
920 E.
58th Street
Chicago,
IL 60637
Ph:
773-834-3597 Fax: 773-834-5337
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