Back to School and A New Pediatric Specialist

We have had a chaotic spring, with the boys' surgeries that took up our lives from late February through mid April. I am so grateful that everyone has recovered! Nolan went back to school today, and was happy to have his routine back.

I recently had a friend tell me about a pediatric specialist in our (relatively) local area who takes on difficult cases. My friend's children are also complex, and this specialist is keen on finding an accurate, global diagnosis for her kids. I am in the process of trying to get an appointment for Nolan, as he needs someone to review his entire case and look at the boy as a whole. Currently, his diagnoses are (organized by system):

ENT:

Chronic sinus infections
Chronic ear infections (5 sets of tympanostomy tubes)
Progressive, mixed hearing loss (currently moderately-severe to severe). Hearing aids.
Laryngomalacia
Obstructive and central sleep apnea - C-Pap user
Glossoptosis

GI:

Severe reflux/Nissen fundoplication with g-tube placement
Gastroparesis
Failure to thrive (supplemental feeds for ~ 800 calories/day)
Chronic diarrhea
Periodic vomiting attacks

Vision:

Astigmatism (both eyes)
Myopia (right eye)
Amblyopia (right eye) - treated with glasses

Urology:

Posterior urethral valves

Cardiology:

Innocent heart murmur in the mitral valve area (echo normal, sounds of regurgitation from mitral valve)

Other:

Hyperflexible joints
Mild hypotonia, primarily in the hands and arms
Fatigue with walking
Unexplained leg pain (severe & periodic)

In any case, I'd be glad to have his entire case reviewed, just to make sure someone hasn't missed something obvious along the way. In addition, I want to make sure that we're treating Nolan appropriately - I don't want to do any more surgeries until we're positive it is the right treatment for his system as a whole.

The pediatric specialist has two "sides" to her practice - a general pediatrics side and a rheumatology side. I am currently waiting to hear back from the office to see which "side" Nolan will be booked under - with the hyperflexibility and leg pain, they may book us under rheumatology rather than general pediatrics.

I just hope they can help us find some answers.

Update From Our Cleveland Clinic Trip: Genetics

We are back from the Cleveland Clinic - an absolutely amazing medical center. Nolan was amazed by the fountains and the landscaping everywhere - there's a reason they call this place "Medical Disneyland." The top-notch doctors make this place truly wonderful.

We saw the geneticist and the genetic counselor, who looked at Nolan's (extensive) medical history and at Nolan himself. I will say up front: there is no "Eureka! We found it!" moment coming up here - so this will be a long post detailing the general thoughts and impressions from the team at the Clinic.

First off, Nolan is definitely medically complex. There are a lot of things going on, obviously, and some things can be considered "birth defects" (the posterior urethral valves and the hearing loss) and some can be considered progressive (the acid reflux with increasing intensity, the laryngomalacia, the hearing loss, the vision). Some things are entirely new to us. Both the geneticist and the pediatric resident heard a distinctive heart murmur.

Nolan's echocardiogram a year ago was declared "normal." No one has ever detected a murmur before. It is likely he has developed a new issue, but the geneticist is requesting his echocardiogram from last year to confirm that this is a new development. If it is a murmur, the location of the murmur suggests that it is a mitral valve prolapse. This is generally a fairly benign murmur that doesn't need surgical correction, but it will need monitoring. We'll see where this one goes.

Hanging out in genetics

The geneticist went over Nolan's issues. Some "separate" issues are really linked together, because one issue causes the other. The truly separate issues are:

1. Hearing Loss

2. Myopia, Astigmatism, and Anisometropic Amblyopia (vision)

3. Severe reflux -Laryngomalacia - Obstructive Sleep Apnea - Chronic ear infections/upper respiratory infections

4. Posterior Urethral Valves

5. Heart Murmur, probably mitral valve prolapse (new)

6. Hyperextensible joints with mild hypotonia

Obviously, this many issues isn't exactly coincidence. On the other hand, there is no comprehensive diagnosis that fits his issues. The geneticist did feel that he should have a genetic microarray done, to rule out minor chromosomal deletions and additions that can cause issues for some kids.

She did warn us that the test will probably come back as "normal," however, because the majority of chromosomal rearrangements and deletions cause cognitive and developmental issues. Nolan has no cognitive issues, which makes a chromosomal problem less likely. We do need to run the test, though, because other things cannot be considered until this test is done and his chromosomes have been checked out.

The microarray was drawn this afternoon and we should have the results in about 2 weeks.

She did say that Nolan was doing well developmentally, so while he is medically complex, he is also very "normal." Which is wonderful to hear... though we do wish there was a way to treat the medical problems he does have (and stop new ones from cropping up)! Essentially, we will have to monitor him on an annual basis and see if new issues keep cropping up.

Heading out: happy to get to the car!

As for the reflux, we have no idea why it continues to increase in severity. We asked her opinion on the fundoplication, and there really isn't a right or wrong answer. If his lungs are definitely affected, we should do it. If it is just the apnea, we should probably stick with C-Pap and try to make it work. If he starts having difficulty maintaining weight, we should do it. Since he has re-gained his weight back to 32.4 pounds (woot!), we might consider holding off.

She did tell us to consider the following very carefully: with Nolan's history, we should be prepared for a fundoplication to completely fail in its goal to eliminate apnea. While it may work, there is no guarantee that it will be successful in controlling the apnea. We could very well do a fundoplication, and then still need to use a C-Pap for Nolan. And we will always have to use anti-reflux meds for him. So really, if the reflux starts attacking his lungs, voice, or ability to grow... we should do the fundoplication. If the reflux is just causing the apnea, we would be better off controlling that with the C-Pap. It will be an ever-evolving judgment call: with progressively worse reflux, our decision to hold off on the fundoplication may have to be reversed as new complications arise.

She also said that his fatigue and stomach pain is an inescapable component of his condition. He has apnea - he is going to be tired until it is well controlled. Controlling apnea with severe reflux is difficult, so he will likely struggle with fatigue. While a little depressing, it is realistic: he has a chronic condition that we will have to cope with, because it is unlikely that it can be "fixed."

His stomach pain comes with the acid-reflux territory. His gut doesn't work right, and he's going to hurt a lot. Again, he will have to develop coping mechanisms for this, and we'll have to try to keep on top of the anti-reflux meds as we have always done. A fundoplication will not fix the mysterious stomach pain (which is likely due to delayed gastric emptying).

Her input was valuable. For now, we will probably hold off on the fundoplication and work harder to make the C-Pap work for Nolan. But our decision may change, based on what the reflux does to his little body.

As for now, we just wait for 2 more weeks to see what the microarray shows.

The Cleveland Clinic: A Cut Above

I was a little worried when I noticed that only about a quarter of Nolan's medical records had been faxed to the Cleveland Clinic. Knowing that we only get one shot at this, I was concerned that the partial records would make for an useless appointment.

I sent in medical records request letters to our ENT, Pediatric Ophthalmologist, and GI doctor, so that some of the missing records would find their way to the Clinic.

Yesterday, the phone rang. It was the genetic counselor at Cleveland Clinic - she noticed that some of the records were missing from the pediatrician's office.

"There is a record mentioning an echocardiogram, but there is no echo. There is a record mentioning an MRI scan, but there is no MRI scan."

"Are there any endoscopy biopsy results? Labwork? Ophthalmology reports?"

"No. There is no mention at all of his vision problems."

"OK, I'll get on that."

There were 54 pages sent, probably about 1/4 of Nolan's medical records. I'm working on getting the rest sent directly from the specialists. The records sent to the Clinic were missing his genetic testing work from 2008 (just Connexin 26, Connexin 30, and mito A1555G, which were all negative for mutations). The records were missing all mention of vision issues, reflux test results, biopsy results, labwork, etc.

The rest of the records should slowly start filtering in to the Clinic this week. I will fax the rest of the missing records (early ABR hearing tests, genetic test results, etc) tomorrow.

I am SO impressed that the Clinic noticed the missing records and called me about them. I honestly don't think anyone has ever sat down and reviewed all of Nolan's medical records before.

We may never have a comprehensive diagnosis, but I am impressed with the attention to detail and the professionalism at the Cleveland Clinic. I feel like I can trust their judgment - they have really looked at his entire case and have seen kids like him before.

I really can't wait for our appointment next month. We may not get answers, but maybe we'll get get pointed in the right direction with our care of Nolan's most pressing medical concerns. Sometimes, getting pointed in the right direction is the most important thing.

Jumping Through Hoops and Some Technical Difficulties

Nolan is the king of pouting. Some days, he has good reason.

The insurance company responded to our pediatrician's pre-authorization letter requesting a genetics consult at the Cleveland Clinic. They said that the authorization will be denied because Nolan has already had genetic testing, and our pediatrician needs to explain why the former genetic testing was insufficient.

So we move on to round 2 of getting approval to get a second opinion.

For the record, Nolan has only had genetic testing done for Connexin 26, Connexin 30, and the mitochondrial A1555G mutation: this is part of a 3-gene "Non-Syndromic Deafness" panel that is standard for nearly all children with hearing loss. His blood was taken at Buffalo Children's and sent to Boston for testing. Nolan was negative for any mutations in those three genes.

All of the "extra" medical issues have occurred since that point in time (he was only four months old during our genetics consult at WCHOB).

Our insurance company claims that Nolan was seen at Boston Children's Hospital, constituting a second opinion. This proves my theory that the insurance company employee reviewing the request cannot read.

The genetics report by Boston Children's is just the analytical data from the blood sample sent to them by WCHOB. We have never been to Boston, we have never gotten a second opinion, and the genetic test drawn by WCHOB and sent to Boston for testing was negative. So we know he doesn't have the most common gene responsible for non-syndromic deafness. This, coupled with the onset of new symptoms (including a machine necessary to keep him breathing at night, vision problems, muscle tone issues, etc.) should be enough to warrant a second opinion from a geneticist.

Hopefully the rebuttal letter our pediatrician is penning will be sufficient to grant us access to Cleveland Clinic. We're not seeking tons of expensive testing: we're simply seeking a second opinion from a clinical geneticist who works for a hospital which has a unit specializing in genetics relating to hearing loss.

In other news, Nolan's right hearing aid died on us today. It had been giving us a low "hum" and eating batteries. We normally go through one set of batteries per week with Nolan, and we started going through a battery per day. Besides the expense of buying a bazillion Size 13 batteries, there was the more pressing concern that Nolan's hearing aid might be ready to kick the bucket. It won't turn on at all today, so he is currently sporting only one "ear" and saying, "WHAT YOU SAY?" a lot. We see his audiologist on the 5th for a repeat hearing test, anyway, so hopefully she'll be able to help us find a solution. I just hope that solution is not buying new hearing aids.

The Letter is Being Faxed

Our pediatrician's office is in the process of drafting a letter to our insurance company, in the hopes that they will authorize our trip to the Cleveland Clinic. They asked me for a general synopsis of Nolan's medical history and our reasons for wanting to go to the Cleveland Clinic, so I sent them the sheet of paper I take to each new doctor (his medical history is now long enough that I can't spit it all out in a few seconds). Here is what that paper looks like:

Nolan's Medical History

Gastrointestinal: Severe GERD unresponsive to medical therapy, mild delayed gastric emptying, slow bolus transit time noted during first impedance probe.

Urology: Posterior urethral valves, ablated in June 2009.

ENT: Obstructive sleep apnea unresponsive to surgical measures (tonsillectomy and supraglottoplasty), chronic otitis media (four sets of PE tubes by age 3) congenital bilateral hearing loss (moderately severe mixed hearing loss), severe laryngomalacia. Wears 2 hearing aids.

Neurology: History of severe central sleep apnea (resolved), mild hypotonia.

Vision: Anisometropic amblyopia (myopic in the right eye); astigmatism in both eyes. Wears glasses.

CURRENT MEDICATIONS:

Nexium, 20mg, 2x per day. Zantac 30mg, 2x per day.

PRIOR HOSPITALIZATIONS and tests:

October 24, 2007: ABR diagnosing mild/moderate bilateral hearing loss.

February 2008: Genetics evaluation: Negative for Connexin 26, Connexin 30, and mitochondrial A1555G mutations (non-syndromic hearing loss panel).

March 18, 2008: sedated CT scan of the inner ear (normal).

March 27, 2008: PE tubes placed (set #1).

August 11, 2008: Sedated MRI of the inner ear (normal).

December 2008: Second set of PE tubes placed.

May 2009: Gastric emptying scintiscan (normal for reflux/mild delayed gastric emptying)

June 1, 2009: Cystoscopy and ablation of posterior urethral valves.

July 9, 2009: Upper GI barium (normal).

August 2009: Endoscopy, 24 hour pH/impedence probe (inpatient: severe GERD detected).

January 20, 2010: Sleep study #1: severe central apnea and severe obstructive apnea.

February 10, 2010: Sleep-deprived EEG (20 minute EEG) for staring spells (normal).

March 23, 2010: Sedated MRI for central sleep apnea (normal).

April 13, 2010: Tonsillectomy, Adenoidectomy, PE Tube Set #3 (inpatient PICU monitoring).

August 2010: Sleep study #2: Severe obstructive sleep apnea, mild central sleep apnea.

October 12, 2010: PE tube set #4 (long term “T” tubes placed), Bronchoscopy: Severe Laryngomalacia diagnosed.

November 10, 2010: 24 hour Pharyngeal pH probe: reflux persistent despite PPI treatment. Zantac added to medication regime to stop reflux.

December 3, 2010: Echocardiogram and EKG (normal).

December 2010: 24 hour Pharyngeal pH probe: some reflux still noted with PPI and H2 blocker treatment.

December 14, 2010: Supraglottoplasty and lingual tonsillectomy (inpatient, PICU).

May 3, 2011: Sleep study #3. Central sleep apnea resolved. Moderate obstructive sleep apnea, persistent despite tonsillectomy/adenoidectomy and supraglottoplasty. Fundoplication recommended by ENT. Bi-Pap or C-Pap evaluation recommended by sleep neurologist. Upper GI barium scheduled for 06/27/11; Sleep neuro exam scheduled for 06/21/11; trying to get into Cleveland Clinic for a second opinion from a pediatric geneticist.

Our reasoning for choosing the Cleveland Clinic for the genetics evaluation site was written as follows:

"Due to the repeated surgical procedures, sleep apnea, chronic ear infections, chronic sinusitis, severe GERD (unresponsive to medical therapy), delayed gastric emptying, hypotonia, urology, vision and congenital hearing issues, we are concerned that there may be a single cause underlying the various symptoms that Nolan has experienced. Prior to consenting to additional surgical measures or procedures (recommended fundoplication; C-Pap), we would like to ensure that no genetic syndrome underlies his various issues. The Cleveland Clinic has a renowned genetics program, including a hearing-loss genetics subunit, which is unrivaled in the area. If there is a syndrome or other “issue” at play, we feel confident the Cleveland Clinic will be able to discover the cause – if there is no underlying cause, then we will feel confident with their assessment that his medical history is caused by separate (unrelated) incidents."

Hopefully the insurance company's doctor will look at his history and approve another genetics consultation without giving us a lot of hassle. Our pediatrician's office has been wonderful and is supportive of us getting a second opinion.

The letter should be faxed to the insurance company today, and we should have an authorization approval within 30 days: once the authorization comes through, the Cleveland Clinic will schedule our appointment with the geneticist. This will likely occur in August or September, as it takes a while to get into the Clinic.

In the meantime, our biggest worry is Nolan's fatigue and general "droopiness." This is due to his hypotonia (we think) - the hypotonia affects his upper body and arms the worst; his feet and legs seem generally unaffected. He still has the head lag, though his development hasn't been delayed by it. Still, the effect can be striking in the afternoons. He fatigues while walking, and gets very droopy while sitting or standing.

Nolan, a little droopy in the afternoon

There is a part of me that wonders if his muscle tone issues underlie most of his other problems. The GI tract is made of smooth muscle, so the slower motility and the reflux would be affected by a muscle tone problem. His obstructive apnea could be due to low tone, in addition to reflux and the persistent laryngomalacia. For kids with late-onset laryngomalacia and muscle tone issues, the airway collapse is due to an intrinsic weakness in the system.

We're extremely hopeful that the geneticist at the Cleveland Clinic will be able to piece this together - and if she can't, that she will be able to reassure us that these issues are not connected and that nothing new will pop up to surprise us in the future.

Sleep Study #3: Report

We had the official sleep study report faxed to us, because we wanted to see what the sleep neurologist's recommendations were. Since our pediatrician's office wouldn't give us the report, and our ENT didn't discuss the recommendations from the sleep neurologist, we wanted to review the report to see what the neurologist would recommend.

the report is like any other sleep study report. This is the best sleep study he has ever had, but there are still significant issues. A brief rundown of the actual data:

Minimum O2 concentration during sleep: 87%
Average O2 concentration during sleep: 98%
Number of obstructive hypopneas: 57
Number of arousals during sleep: 125
Respiratory Disturbance Index (REM sleep): 20.1
Respiratory Disturbance Index (non-REM): 7.6

For most people, that's a lot of mumbo-jumbo. A normal Respiratory Disturbance Index for the pediatric population is <1.5: Nolan is obviously above this threshold during any sleep stage. He woke up 125 times during the study. The good news is that despite occasional oxygen desaturations, his average oxygen level is great.

He isn't retaining CO2 yet, which is important. Children who retain carbon dioxide effectively poison their systems with the retained gas - Nolan's CO2 levels were 42mm Hg on average, which is in the normal range.

The sleep neurologist's recommendations read:

"Despite improvement compared to previous study (8-9-10), these findings indicate the ongoing presence of obstructive sleep apnea (for the pediatric age range normal RDI <1.5) consisting mainly of hypopneas with associated disruption in sleep architecture and oxyhemoglobin desaturation, especially in REM sleep (RDI: 8.6, and minimum oxyhemoglobin concentration 87%). If clinically indicated, evaluation by ENT for persistent airway abnormality should be considered. If this has already been performed, a return to the lab for nasal C-Pap or BiPap (given history of hypotonia) titration could also be considered. Clinical correlation is suggested."

I called the sleep neurology center and made an appointment for June 21. I want their take on his situation, and advice on doing a C-Pap or BiPap with the presence of persistent reflux.

While I was at it, I called the Cleveland Clinic and started the process to get into the genomics division at that center. Our ENT feels strongly that Nolan does not have a syndrome. I am not sure whether there is an underlying disorder causing his issues or not, but we are not consenting to any more surgery until we can verify that there is no underlying neuromuscular, genetic, or metabolic problem. The Cleveland Clinic has to get financial approval from our insurance company, so we sit with baited breath waiting to hear back from financial services and the genomics department. If our insurance approves the appointment, we could get in as early as late July or August. If nothing else, getting an "all-clear" from a fresh set of eyes will make us feel better and make better decisions for Nolan.

An Informative Visit with Dr. B

We had our appointment with neurologist #2 today, and it was a much better visit. She was much more thorough with Nolan's medical history, and had a clear sense of direction for the treatment of Nolan's central apnea. We also learned a few new things today- not that they are really "new" things, but confirmation of things we have always noticed with the little guy.

As far as the central apnea, we are on the right course. The MRI must be done first- to absolutely rule out a Chiari (even though this is unlikely) and to verify there is nothing amiss with Nolan's brain. She also agreed that a tonsillectomy was a good idea, to get rid of the obstructive component.

We did learn that central sleep apnea (CSA) is rare enough that there really isn't a standard treatment protocol for children with CSA following a tonsillectomy. We have two options- to forgo the Tylenol with Codeine in favor of regular Tylenol, or to try and obtain an apnea monitor for those two weeks from Pulmonary and keep the little guy on the codeine. Codeine is a respiratory suppressant, so it isn't really safe to have him on the medication without a monitor. The neurologist is going to talk to our ENT to plot a course of action.

We are going to wait a full three months after the tonsillectomy to have a repeat sleep study. This is to give Nolan time to heal completely, and for all residual swelling to dissipate. We will do the follow-up sleep study in early August, with a follow-up appointment the week after. If the central apnea is still there in measurable quantity, we will pursue artificial ventilation at night via V-Pap (a special version of biPap for central apnea).

As far as the rest of Nolan's symptoms, she does feel that another visit to genetics is warranted. We won't go back to the original geneticist, because he was completely off base.

Remember the worry about frontal bossing? Yeah. The neurologist confirmed that it is there. So we can add that back to the roster of symptoms.

Also, remember the head lag? She did a brief work-up and told us that he has some decreased muscle tone (hypotonia) in his arms and trunk. It is mild, but another piece to the puzzle.

I do have the name of a geneticist at Cleveland Clinic, and I think we'll attempt any further genetic work-ups there. We haven't had much luck at Buffalo Children's (CHOB).

For a brief re-cap, here's the "list of symptoms:"

Congenital moderate hearing loss
Posterior urethral valves
Failure to thrive (resolved)
Severe GERD
Mild Delayed Gastric Emptying (DGE)
Mild frontal bossing
Mild hypotonia
Elevated AST (liver or muscle enzyme marker)
Periodic temperature fluctuations
Periodic rash on trunk
Chronic otitis media
Severe obstructive sleep apnea
Severe central sleep apnea

Dr. Block called this "multi-system involvement," and does believe a syndrome is at play. The question is, which one?