When Naomi was three, Emma was born and it was at this time that our new kidney doctor told me we were dealing with a genetic polycystic kidney disease, but which polycystic kidney disease was still unclear. The summer of 2008, when Emma was nine months old we flew to the National Institutes of Health in Maryland and were told the girls had an atypical variant of Autosomal Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis (ARPKD/CHF). They told me "We might not have the exact house number, but we're in the right neighborhood," with that diagnosis.
An atypical variant of ARPKD/CHF has been our working diagnosis ever since, but this never satisfied me either. The kidneys of children with ARPKD/CHF are almost always enlarged (at least at first, before they atrophy from renal failure), but my girls' kidneys had always been small. Most children with ARPKD/CHF have high blood pressure, especially by the time they reach the stage of renal failure that Naomi is in, but neither of my girls have ever had high blood pressure. And most other children with ARPKD/CHF develop typically in every other way, except for the complications of kidney and liver disease.
As Emma grew we dealt with chronic, recurrent ear infections, severe speech apraxia, more global developmental delays, and were told that there was a generalized slowing of all of her brainwaves on both standard and 24 hour EEG, called encephalopathy.
When Naomi was diagnosed with celiac disease, her diet was changed, and her intestines healed she began to pack on weight at an alarming rate. Further diet modifications and implementation of some healthy eating habits helped for awhile, but over the last year and a half it has been near impossible to slow Naomi's weight gain.
On top of this mystery: Toby was born with his right kidney small and stuck to the bottom of the left kidney, sitting like a backwards L in his abdomen; Hannah's kidneys are consistently measuring far too small for her age; and Elijah is dealing with persistent, mild anemia that doesn't want to improve with iron supplementation. Both Toby and Elijah have had horrendous chronic ear infections. All my babies were plagued with asthma, at least for the first three to four years of life.
And I wondered: What went wrong? Is there even one explanation out there for all of this, or is this a cosmic collision of coincidental conditions among my kids? But I seemed to be the only one who thought it mattered much. Naomi and Emma's current doctors felt that we could only treat symptoms as they arose, regardless of what caused them.
Until that changed, on Tuesday January 14th, we met Naomi's new kidney doctor at the children's hospital, in anticipation of the kidney transplant she will doubtless need in the next couple years. Dr. W reviewed Naomi's history and told me she was not confident in the diagnosis of ARPKD/CHF (for the reasons listed above). She was not questioning that Naomi and Emma have cystic kidneys and liver fibrosis, that much has been confirmed time and again on imaging studies, she wanted to look for a diagnosis that would better account for the whole clinical picture of what Naomi and Emma live with, and possibly for the abnormalities my other children have as well. Dr. W told me she would schedule Naomi to see a geneticist, and that they would send Naomi and Emma's blood to a specialist in Boston for genetic testing for a disease called Bardet-Biedl Syndrome (BBS).
I had heard of BBS before, and had looked into it briefly because this syndrome causes cystic kidneys, liver fibrosis, and many developmental delays; but at that time several of the main features didn't seem to fit my children, and I had dismissed it. I had read that BBS was characterized by obesity, and at that time Naomi did not struggle with obesity (I had no idea that it was undiagnosed celiac disease which had destroyed her intestines that was keeping the obesity at bay). About two-thirds of patients with BBS are born with extra fingers and toes, which also didn't fit my girls. And lastly, 100% of patients with BBS develop a retinal dystrophy that eventually leads to blindness. Five years ago, it didn't fit, and I was happy to cross that scary possibility off my list, and put it out of mind…until Tuesday, January 14th.
When I looked at Bardet-Biedl Syndrome afresh over the following days I realized it explained more of my family than any diagnosis before could come close to explaining. It is an extremely rare and complicated disease that can be caused by mutations in over 14 different genes, and the inheritance pattern can be equally complicated depending on how many and which mutated genes of that list each parent carries. If the mother carries two or three different mutated genes and the father carries two or three mutated genes, then the children could each be born with a different degree of illness, depending on the specific combination they inherited.
The following are the diagnostic criteria for BBS. Diagnosis requires four primary or three primary plus two secondary characteristics:
Primary features:
? Rod–cone dystrophy
(this is the degeneration of the retina in the eyes that often doesn't develop until the teen years, so we don't know about this yet)
- Polydactyly
(extra finger or toes, found in 2/3 of BBS patients, we don't have this)
+ Obesity
(yes for Naomi, and Emma tended this way for her first three years)
+ Learning disabilities
(yes for both girls, although Naomi is brilliant in ways, she also has her struggles)
- Hypogonadism in males
(they're not male, so this is a mute point)
+ Renal anomalies
(obviously, yes for both)
Secondary features:
+ Speech disorder/delay
(yes for both, Emma more severely, but Naomi's speech is disordered as well)
+ Strabismus/cataracts/astigmatism
(Naomi has strabismus, Emma has astigmatism and myopia)
- Brachydactyly/syndactyly
(webbed fingers and toes, nope, but some lists add here "clinodactyly" which is a curling in of the fifth finger and toes, which all my kids have)
+ Developmental delay
(yes for both)
+ Polyuria/polydipsia (nephrogenic diabetes insipidus)
(this is extra urine and extra thirst, which is yes for Naomi only, but her case is quite severe)
+ Ataxia/poor coordination/imbalance
(yes for both)
- Mild spasticity (especially lower limbs)
(no, but both girls have low muscle tone, which some lists also include here as an alternate presentation)
? Diabetes mellitus
(this one, like the rod-cone dystrophy, usually develops later in life, so we shall see)
+ Dental crowding/hypodontia/small roots/high arched palate
(Naomi has dental crowding and hypodontia, Emma has small dental roots (which explains her teeth suddenly falling out) and a high arched palate so between the two girls we have all of these)
? Left ventricular hypertrophy/congenital heart disease
(Both girls have heart murmurs, Naomi has a valve that sometimes leaks and sometimes doesn't)
+ Hepatic fibrosis
(yes for both)
Between the two girls we have at least three primary features and at least seven secondary features of Bardet-Biedl syndrome, which is more than enough for a diagnosis. I will spare you the lengthy details, but the more I've read the more I am convinced that this syndrome fits. The specific kidney anomalies, the specific behavioral problems encountered, the specific speech deficits, the specific neurological deficits and coordination problems, all line up exactly with Naomi and Emma's diagnoses. Many patients also struggle with chronic asthma and chronic ear infections. Many require ear tube placement. Even more astounding is the fact that several studies found many siblings of BBS patients have milder manifestations of the disease, including several siblings who had missing or misplaced kidneys like Toby's. None of that is true of ARPKD/CHF.
I have mixed emotions over all of this, obviously. It is a relief to solve the mystery and lay my years-long search to rest, though I doubt I'll rest completely until the specific gene mutation(s) are found. There is some good news as well: only 5-10% of BBS patients reach end-stage renal failure. We know for certain that Naomi will, she is past the point of no return with her struggling kidneys, but this gives me hope that Emma, whose kidney function has always been completely normal, may not ever need kidney transplantation. This is the first time that hope has been offered to me.
But, sadly, there are so many more things that grieve me over this diagnosis, not least of which is the news that, if this diagnosis is accurate, we face the near 100% certainty that both girls will lose their eyesight in early adulthood, with an average onset of legal blindness by 20 years of age, and only a few patients making it past 30 with some preserved sight. I am trying to remind myself here that their gene mutations have not yet been identified, and that there is a possibility we carry a novel mutation that causes a BBS-like syndrome without the retinal dystrophy. It's possible, but I don't think it's likely. Some of the early signs of this retinal dystrophy are photophobia (fear of bright lights), which Naomi has had since day one, and myopia (near-sightedness) which Emma has had at least since she was three. Usually vision deteriorates around the periphery first, and slowly closes in over a decade or so until nothing remains. I have always had concerns about Emma's peripheral vision, and the changes are subtle and difficult to detect at first, even for an experienced ophthalmologist. You really need an electroretinogram to detect these subtle changes, something I'm hoping the geneticist will refer the girls for soon.
The mutations in the BBS genes cause mutations to several proteins critical for the proper functioning of many types of cells in the body: kidneys, liver, eyes, brain, heart, reproductive system, lining of the respiratory tract, and more. Without the proper protein functions these cells manage to function for awhile, but tend to die off early leading to progressive loss of function in the affected organs. Which means that we may be facing not only kidney or liver failure, but blindness, diabetes, and possibly (though less likely) heart failure, deafness, and more. Equally terrifying is the possibility that my other three children may be affected as well, even if much more mildly. There is something so comforting about a strictly "autosomal recessive" disease: either you have the disease, carry the disease silently, or you're not at all affected. But BBS is more complicated than that and siblings are often mildly affected. This could explain Toby's weird kidney, Hannah's small kidneys, Hannah's heart murmur, Elijah's anemia, and the chronic ear infections and asthma. But this obviously puts them all at risk of developing other manifestations of BBS later in life, which, even if unlikely, is terrifying.
Because research into this disease is so young, only time will tell. It will still be several months before we can see the geneticist, and up to six months after that before the mutations are identified. When Naomi and Emma's mutations are identified we may check the other children as well. Dr. W surprised me by saying that of my three other children she was most concerned that Hannah may have a form of this same disease because of her very small kidneys. And so we wait. And I think that is the hardest part.
So there it is: my very cold, factual detailing of Naomi and Emma's likely new diagnosis, and how that changes the outlook for our entire family's future. I've been digesting this more quietly the last few weeks, but decided I might as well come out with it. Given the amount of time it could take to confirm the genetic mutation, it didn't seem like a good idea to try to wait for that, and it would be nice to feel like the people around me understood what I was going through in the meantime.
My next post will be a poem I've been working on, more of the emotional side of all of this. Thank you all for reading and caring.
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