Hypotonia, Developmental Delays, Undiagnosed

[Jessie]

I am the mother of a 20 month old little girl who is hypotonic, has some optic nerve atrophy, nystagmus, strabismus (left eye deviates outward), and is developmentally delayed. Despite the visual diagnoses, she functions as though she were a normally sighted child and the strabismus is markedly improved from a year ago. She is cruising, but not walking. Her fine motor skills are delayed, but improving. Her speech is quite delayed. She only babbles, but she used to use some words such as  "book" and "dog."  Her receptive language is normal and we feel she is of average intelligence. She is very tall and thin, head size is in the 95th percentile, she has flat feet and long fingers and toes. She's a good eater and is growing well.
At 5 months she had a normal MRI. She has undergone extensive blood and urine testing. I'm not sure of all the tests, but I know her cholesterol, pyruvate, lactate, and organic acid levels have come back normal. She has had a normal karyotype and mitochondrial DNA tests. We have not done a muscle biopsy.
Furthermore, she experiences episodes in which she seems to lose her balance. Her arms fly out, she breathes very rapidly, and cries. It's as though she feels she is falling, and this is quite scary for her. It happens most often when she is placed somewhere, such as being layed down on her changing table. She's had a normal EEG.
While my daughter continues to progress and is a happy, delightful little girl, I continue to look for a diagnosis. I know we may never find one, but I'm wondering if you have any suggestions as to which direction we should look in next.
Thanks in advance for your reply.

[CCF Neuro[P] MD, RPS]

Dear Heidi:

I think the really good news is that your son has a normal MRI and EEG of the brain.  With multiple defects, one assumes that the brain will be malformed.  Although Penna-Shokeir the usual problem is the pulmonary hypoplasia, that compromises the baby.  But I am sure you already know this.  This disorder is such a rare entity, that I only have read about it and actually never have seen a case.  I would imagine that since the reported literature indicates that 15 out of 17 had abnormal muscle histology, this is the reason for the hypotonia.  Your pediatric neurologist can explain the hypotonia to you, probably better than myself.  But muscles need a certain tone or resting tension to function properly.  When the tone is decreased, muscle strength may be decreased and certain activities requiring muscle coordination may be compromised.  Your son will likely need PT and OT to help him with muscle function.  But since the hypotonia is mildish, the need will likely only be mild also.  Let us know how he does.  The muscle biopsy is important to see if the hypotonia is muscle in origin (a good possibility)

Sincerely,

CCF Neuro MD

[heidi]

Dear Doctor,

To answer your questions, my understanding of why an MRI and EEG were conducted was because of the individual things that were wrong with the baby, with no known cause.  The baby was born with the lung issue, as well as a cleft palate, clenched fists, and clubbed feet.  Also, I had polyhydramious during the pregnancy.  During a level II sonogram, when these things were discovered, we were advised that the baby may have penna shokier (sp?) a rare disease, that included low muscle tone as well as the other physical symptoms listed above.  Since I last wrote, another MRI and EEG were performed, again showing no significant abnormalities.  The baby is able to turn his head, lift and stretch his arms, lift his legs (even though they are casted from his thighs down), and cries loudly.  I have been advised by the pediatric neurologist (who has been involved in his care from the onset) that he has moderate hypotonia, but to date, there is no known cause.  They plan on watching his progress for the next week and if he does not improve, they plan on doing a muscle biopsy.  I understand that his future can not be predicted, but I did not know if you could give me some insight into what hypotonia does to a child, and if there is a specialist that you are aware of that I should contact.  Looking forward to your response.  Thank you.

[CCF Neuro[P] MD, RPS]

Dear Heidi:

Sorry that your child was born prematurely.  Why did he have an MRI and EEG?  These are not common tests in the premature.  Who diagnosed the hypotonia?  Immature lungs at 35 weeks is very common and not unusual.  Only two weeks on mechanical ventillation is really good.  Since the MRI and EEG were normal for age, there is no reason to assume your child will have neurological problems.  Hypotonia can be due to alot of things and one will need to see how your child's muscle tone progresses.  What is reason for the hypotonia?  I would make sure that a pediatric neurologist be seen somewhere down the line, especially if the hypotonia persists.

CCF Neuro MD

[heidi]

Dear Doctor,

I am the mother of a three week old baby boy who was born at 35 weeks.  I have been told that he has hypotonia, along with other issues.  He had severly immature lungs and had to be placed on a ventilator for almost two weeks.  He has undergone an MRI which showed no abnormality and an EEG which also showed no abnormalities.  His hands remain in a clenched fist, although they can be opened.  As a mother who is just learning of this, can you please explain what type of future am I expecting for my child.  I understand that he may be developmentally slow, but I am not sure exactly how hypotonia effects a child.

I look forward to your response.  

Thank you,

Heidi

[CCF Neuro[P] MD, RPS]

Dear Kass:

The better test is a electron micrograph of the biopsy muscle tissue.  We find a correlation with increase mitochondrial number and metabolic disease.  The light microscopy stains may or may not give one an answer when mitochondrial disease is suspected.  This is because the tests are rather insensitive to subtle changes of mitochondrial function.  

Whether your son and daughter may have the same thing, metabolically I can not answer.  I have no physical exam, lab data etc to try and associate the two.  Yes, it is possible.  We have seen such families.

I would send the urine organic acids to Dr. Richard Kelly's lab at the Kennedy Krieger Institute at Johns Hopkins.  Most labs do an okay job with the amino acids but make sure that the reference values are tight.  We send our carnitines to Dr. Hoppel at CIDEM at Case Western Reserve University.  We make sure that the lactate and pyruvate levels are drawn properly and measured immediately.  Dr. Hoppel processes our fresh muscle biopsies.

I hope this helps, sorry I can't help more.

Sincerely,

CCF Neuro MD

[kass]

Dear Doctor,

Not to jump in here, but as another mom of a hypotonic little girl (3-delayed myelin/fiber type I predominance/staining indicating mito disorder on one slide that may, or may not, be artifact on biopsy) your response was of great interest to me. Could you please share again with us whom the bloodwork can be sent to for an accurate metabolic work up??

I also have a son with an autism spectrum disorder and suspected seizures, and we are looking to see if maybe this is the connection between my two kids (something metabolic). In your experience, is it likely that there is a connection between two kids in the same family with issues like this??

Finally, what percentage of children don't show the changes on the biopsy and still have something mitochondrial going on??

If it's a problem that I have posted under Jessie's post I apologize...hopefully the info will be of use to her also.

Sincerely,
Kass

[CCF Neuro[P] MD, RPS]

Dear Jessie:

Your daughter sounds very much like the many infants in my practice.  Unfortunately, we do not find the etiology of some of these patients.  In some we do.  In the majority of patients we find an etiology, it is a disorder of metabolism  Many are mitochondrial, some are other metabolic causes.  Many times the test come back normal and yet they have a metabolic disorder.  It depends on when the tests were performed (stressed by starvation or not), where the tests were sent, who is evaluating the "so-called normal" values, and the extent of the testing.  We find many children that we suspect to have a metabolic disorder (28/30) have had abnormal MRS scans.  Most, but not all have abnormal mitochondrial numbers in their muscle biopsy and a select population of these have a disorder of oxidative phosphorylation by ETC studies.  The decision to get a muscle biopsy is not trival.  We recommend if it is done, to be a fresh sample for evalutaion.  There are only a few places in the country that will examine muscle mitochondrial ETC on fresh muscle.  It is very encouraging to note that your daughter is progressing developmentally.  Her metabolic disorder for now is likely not bad.  

It is impossible to give you a diagnosis over the internet, as you likely know.  I hope your daughter will do well and develops her full potential.

Sincerely,

CCF Neuro MD