| 1. Is there a correlation between the findings on MRI and the severity of the condition?
That is a very good question. Our experience up to now does not show a direct correlation between degree of cerebellar vermis hypoplasia and severity of Joubert symptoms. But we haven't collected enough data to be able to look at that connection. In those rare cases where there are other structural brain abnormalities aside from the cerebellum and brainstem, the children tend to do worse, but that is based on observations rather than rigorous surveys or measurements.
At this time, we mostly use the molar tooth sign to help in diagnosis rather than prognosis (predicting symptoms). Our ability to predict degree of symptoms is very poor. Even within the same family, there can be significant differences between 2 children with Joubert syndrome. We hope that as we collect more knowledge about this condition, and review more MRI scans, we will be able to offer better information about prognosis.
2. What advice can you give for my school-age child with Joubert syndrome who sleeps poorly?
Here are some basic recommendations to improve sleep for children who have a difficult time falling asleep or sleeping through the night. If possible, eliminate naps. Try to establish a calm, cooling-down ritual for the couple hours before bedtime (turning down/off the TV when trying to get a child to bed, for example, can be a big help). Avoid fluids the last hour before bed because even if a child is not wetting, a full bladder can be a signal that will wake a short sleeper. Try to keep a consistent early morning wake-up time (some parents are so exhausted they let their children sleep in late after more tiring nights, but this just adds to their sleep schedule problems). If these measures have been done/tried/failed, then melatonin may be a consideration, but consult your physician first.
A useful book that may provide additional advice is "Sleep Better! A Guide to Improving Sleep for Children with Special Needs" by V. Mark Durand, Ph.D., (Paul H. Brookes Publishing Co., 1998).
Keep in mind that some school-age and adolescent children with Joubert syndrome have obstructive sleep apnea, which means that their airway does not stay open when they are asleep due to enlarged tonsils, adenoids, and/or tongue. A child with sleep apnea may wake many times per night as a result of the obstruction to air flow. If this is the case, the child may need surgery to remove the tonsils and adenoids. In some cases, a CPAP machine can provide some help. A sleep study (or polysomnogram) is recommended if there are concerns about obstructive sleep apnea. Much as infants with Joubert syndrome require a sleep study to look for evidence of breathing pauses or apnea that can be life-threatening, older children with Joubert syndrome may also need a sleep study, for different reasons. Ask your physician if this may be a possibility for your child.
3. Is there a connection between Joubert and Autism?
There is a connection, but it remains somewhat unclear. Autism is a relatively common condition, occurring in 1 in 500 children, and is more likely in boys with a 4:1 male:female ratio. There are likely many different causes for this increasingly common diagnosis. Features of classical autism include poor eye contact and limited communication skills as well as repetitive or self-stimulatory behaviors. Autism has been reported in a number of children with Joubert syndrome in several publications [Holroyd et al 1991; Ozonoff et al 1999]. However, more recent surveys suggest that these behavioral disturbances do not represent classic autism, but are more likely to be related to the underlying cerebellar disorder, eye movement problems, and associated developmental disabilities [Takahashi et al 2005]. It is likely that some children with Joubert syndrome have one or more features that are considered part of the diagnosis of autism, but in our personal experience, few children and adolescents with Joubert syndrome would be described as “autistic.” The behavioral and communication issues that children with Joubert syndrome often manifest can be challenging, but are not typical for the communication disturbances and lack of social connectedness seen in children with autism. Some children with Joubert syndrome seem to process sensory information differently, and similar types of issues can also be seen in children with autism. However, the severe problems with balance and coordination in Joubert syndrome are not typical of autism, as many of these children have normal muscle tone and motor skill acquisition.
4. Could the crying, temper display etc. of toddlers/preschoolers be connected to frustration and feeling trapped in their bodies?
It is hard to know whether these sorts of behaviors are related to feelings of being trapped in their bodies, as many young children are unable to verbalize such specific feelings. In general, behavioral problems, including impulsivity and temper tantrums, have been described in some children and adolescents with Joubert syndrome, but are not found in all [Deonna & Ziegler 1993, Hodgkins et al 2004]. In addition, the sensory processing challenges exhibited by some children with Joubert syndrome may result in out-of-control behaviors such as crying and temper tantrums. Emerging evidence from studies of individuals who have had surgery on the cerebellum indicates that intact cerebellar function may be important for emotional regulation [Schmahmann and Sherman 1998]. It is difficult to know precisely what triggers may exist for an individual child, and different children may have different triggers for their emotional outbursts. Some of these behaviors are also considered normal for children without Joubert syndrome in this age group.
5. What about urine/serum tests? protein metabolism tests?
This question is difficult to answer without more information about the specific types of tests that are being discussed. In general, we recommend annual screening for the potential kidney and liver complications that can occur in some children with Joubert syndrome. Testing for kidney problems includes a urine study called a urinalysis to look for the specific gravity, which is a measure of how concentrated the urine is. (The urine sample can be collected in a clean urine cup—it does not need to be sterile). When children first wake up and urinate, that urine is usually the most concentrated within a 24-hour time period, assuming they did not drink or urinate during the nighttime. Children with early symptoms of nephronophthisis, or one of the kidney conditions we worry about, usually have very dilute urine, tend to drink a lot of fluids and urinate frequently. An annual blood pressure measurement to detect any early signs of high blood pressure is also recommended. Other tests for kidney function include serum tests for creatinine, blood urea nitrogen (BUN), and a complete blood count (CBC) to look for a low red cell count that indicates anemia. Believe it or not, the kidneys make a hormone that stimulates blood cell production in the bone marrow!
The evaluation of liver function may include blood or serum tests for transaminases (ALT, AST), albumin (a measure of protein in the blood and an indirect measure of liver function), and bilirubin, among others.
In addition, abdominal ultrasound scans on an approximately annual basis are recommended for children with Joubert syndrome to screen for signs of kidney damage and liver dysfunction, although these are more likely to occur later in the disease process. ( Please refer to the Joubert Syndrome Foundation and Related Cerebellar Disorders website at http://www.joubertsyndrome.com/ and the “Evaluation Recommendations” link for a complete listing of recommended annual tests).
If “protein metabolism tests” refers to an enzyme deficiency, no consistent metabolic disorder has ever been discovered in children with Joubert syndrome.
6. There is concern about liver involvement and high liver enzyme levels?
Yes, see the answer to question 5 above. Since we cannot predict which children might develop liver fibrosis or scarring, we recommend that children have annual blood test screening for early indications of hepatic (liver) dysfunction. Elevated liver enzyme levels are a sign of liver injury. In our experience with a number of children with one of the Joubert-related disorders, COACH syndrome (Colobomas, Oligophrenia, Ataxia, Cerebellar vermis hypoplasia, Hepatic fibrosis), the earliest symptoms of liver involvement are often elevated liver enzymes or enlarged liver and/or spleen on palpation of the abdomen during a physical exam. We estimate that ~5% of children with Joubert syndrome will develop liver involvement.
Keep in mind that there can be many causes of elevated liver enzymes aside from fibrosis, including a transient viral infection, certain medications such as depakote (valproic acid) or other drugs used to treat seizures, and exposure to certain chemicals. If a child has elevated liver enzyme levels without a known cause, the most appropriate step is to have a physician examine the child and repeat the tests in a few months to see if they return to the normal range.
7. There is a good deal of discussion about supplements and natural additives to help with bodily functions, attention retention, sleeping, and general well-being. How do our Doctors feel about these things?
That is a really difficult question to answer, because each supplement should be considered on its own merits, and on a case-by-case basis. Although a specific supplement may appear to help a given child with sleep or attention, it is quite difficult to generalize to all children, and in fact, may be dangerous to attempt such generalizations. The concern that many physicians have with supplements and natural remedies is that they are not tightly regulated, and the actual content can vary from batch to batch and from manufacturer to manufacturer. Some of these supplements may contain high amounts of substances that could be harmful for a child. For example, mega-doses of some vitamins that are fat-soluble can build up in the body and be toxic to the liver. In addition, a child with increased risk to develop kidney disease should not be taking a protein-rich supplement, as this can put added stress on the kidneys and accelerate the development of kidney problems. I would recommend consultation with a local expert in natural remedies (such as a Naturopathic physician or Medical physician trained in this field) who is also aware of the health risks specific for children with Joubert syndrome and is qualified to provide appropriate guidance and monitoring for use of these supplements. (You can direct such a health-care professional to the Joubert Syndrome Foundation and Related Cerebellar Disorders website at http://www.joubertsyndrome.com/ and the “Evaluation Recommendations” link for a complete listing of recommendations for health care monitoring).
References:
Holroyd S, Reiss AL, Bryan RN (1991) Autistic features in Joubert syndrome: a genetic disorder with agenesis of the cerebellar vermis. Biol Psychiatry 29:287-94.
Ozonoff S, Williams BJ, Gale S, Miller JN (1999) Autism and autistic behavior in Joubert syndrome. J Child Neurol 14:636-41.
Takahashi TN, Farmer JE, Deidrick KK, Hsu BS, Miles JH, Maria BL (2005) Joubert syndrome is not a cause of classical autism. Am J Med Genet A. 132A(4):347-351
Deonna T and Ziegler AL (1993) Cognitive development and behavior in Joubert syndrome. Biol Psychiatry 33:854-5
Hodgkins PR, Harris CM, Shawkat FS, Thompson DA, Chong K, Timms C, Russell-Eggitt I, Taylor DS, Kriss A (2004) Joubert syndrome: long-term follow-up. Dev Med Child Neurol 46:694-9
Schmahmann JD and Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121 ( Pt 4): 561-79.
Answers provided by Drs. Melissa Parisi, Dan Doherty, and Ian Glass. |
