We have one son who was PTN11 Noonan Syndrome and another son who has a clinical diagnosis. Last year, the son with the clinical diagnosis was retested for Noonan Syndrome and was found to have a chromosome sex duplication. Should we have our other son retested? Is it possible for a Noonan’s child to carry another duplication?

This is a possibility as just because you have a particular gene test result for Noonan Syndrome doesn’t mean there wouldn’t be other things. That can sound worrying but actually differences in genetic material are really common and if we look closely enough we’ve all got them. Larger differences that can have an effect are a bit less common but it would be wise to get it checked out.

We have a 4½-year-old daughter with Noonan’s Syndrome who is currently PEG fed. She’s happy to play with food and sits with us when we’re having meals. I just wondered what the range is that’s normal for Noonan kids who are not eating to start, and ask if there are any tips that may help them towards eating. Her gene change is K-Ras.

Of the K-Ras patients we’ve met across the years, they have had more prolonged and more severe feeding difficulties than is typical for Noonan Syndrome. I don’t know if that’s something that’s been obvious to you for a while from your meetings with professionals, but some people with K-Ras gene changes have been described originally on a clinical basis as having CFC syndrome and the need for PEG feeding would push you towards a diagnosis of CFC. It is unsurprising to me to hear that it’s K-Ras that she might have because we have seen other people with K-Ras changes who have need a PEG for four to six years. If we look at the example of Costello Syndrome where nearly everybody ends up with a PEG, it’s very unusual in Costello Syndrome not to be feeding by age eight. I’ve only ever met one patient out of say seventy or so who wasn’t feeding at age ten, so it’s a question of expectant optimism, even though it’s quite hard to understand, we don’t know why feeding is such as issue. It’s worth saying that a lot of parents will have experienced some feeding difficulties but not on this scale, and there are some useful tips from speech and language therapists about trying to encourage certain flavours to help get over the tongue thrusting that’s very difficult in the early stages, and we certainly have had sessions in previous meetings on feeding difficulties so it’s maybe something to think about for other meetings in the future.

Do we know what it is about Noonan’s that causes feeding issues? Is it because of the small stature that they don’t need as much to eat, or is it because they don’t eat as much and they’re bad eaters (generally speaking) and that’s why they have a short stature?

We did originally start looking at the feeding difficulties and it’s almost like a neuro-muscular in-co-ordination – small children can’t chew and that’s later sometimes in children with Noonans where there’s a delayed maturation. There’s also sometimes a problem with the sensation of food in the mouth and the children will sort of “tongue-thrust” and push the food out. But I think it’s basically a neurological control of the feeding; it’s not because they’re small and eat less, and they tend in most cases to get enough nutrition in but will be cases where you need to tube feed children with Noonan’s to begin with and that group needs quite careful follow up from the nutritional point of view.

Is there research into children who are tube fed longer term, e.g. at age 11, and is this physiological or behavioural?

At the present time, research was at the stage of looking at patient surveys and considering anecdotal evidence as to what works. For some families the introduction of a blended diet through the peg tube seems to have been effective but there was no hard and fast rule and it was very difficult. It seemed certain that feeding and speech difficulties were closely related and to get anywhere with research, it would require psychologists and speech and language therapist all working closely together.

A friend has been diagnosed with Leopard Syndrome and she is now thirty years old. She has reflux and sometimes she can’t eat for about seven weeks. She goes in and out of hospital because of dehydration. Are these problems common?

Cyclical vomiting and spells of dreadful sickness are some things that we have recognised in some of our patients with CFC and Costello Syndrome in particular so that probably suggests that it happens for some people with Noonan Syndrome too. The treatment of cyclical vomiting in general is very difficult. A gastroscopy is required and in severe cases further investigation. If this a new onset of needing Oxygen and being unable to tolerate food it needs to be treated as seriously in her as it would be in any thirty-year-old and not be dismissed just because she has a syndrome. We have seen in Costello Syndrome people get development of new reflux, secondary to a chiari malformation in adult life so if she hasn’t had a brain scan with imaging of her posterior fossa, that might be worth doing.

From early on, my child has had feeding difficulties and from that there has been an impact on language development and behaviour with food. Is there any advice?

It can be difficult getting a child to feed who might not be able to feed well or who has an aversion to feeding. It can become a bit of a family struggle and there can be a behavioural aspect developing from it. It’s useful to break down exactly what the problem is because it may be an immaturity in terms of swallowing, sometimes it can be tongue-thrusting – when you try to put food in, it’s pushed out. By analysing that, you can sometimes come to a programme of treatment with the therapist which will improve the feeding.
One parent found that giving a child with the tongue-thrusting issue, spicy and highly-flavoured food eventually led to him starting to enjoy his food although it took time. Speech and language involvement is extremely helpful for a personalised plan.

My son’s calorie intake apart from his peg is about zero, so nothing else is introduced into his diet—are we missing out on anything?

Calorie milk should have the full range of nutrients your child needs going in through the peg so you shouldn’t have to worry. Some parents have opted to tube feed with a blended diet. It’s not sanctioned by the British Dietetics Association but it’s very widespread.

To be really unscientific, I think from my personal experience that my son doesn’t actually get hungry. I think there might be a problem associated with Noonan’s about feeling hunger. My question is around my son—he’s got a peg, he’s 6 so all he has is his nutrients, his pectorin milk, and water that we give him. Now, should we be thinking of supplementing that with anything else now he’s getting older and older and there doesn’t seem to be any coming future in actually eating different food and fresh fruit and vegetables? Should we be thinking about supplementing his diet with anything else other than this milk and water?

I probably don’t know enough to say how common not feeling hungry is although you definitely see that in some children because just like adults, we have variable appetites. I think the most important thing with regard to diet and calories and vitamins is to be under a good dietician who can add up the number of calories and know what vitamins and things to take. The other thing I would say is once you’ve got a good dietician who’s making sure your son or daughter’s getting the right number of calories is to not actually make the food too much of an issue. What you don’t want is for food to become a battle every mealtime because once you know they’ve got good calories in; you want to make food a pleasurable experience and that’s what you focus on. I think the other thing is they say that most children will need to taste a new flavour at least 15 to 17 times before even thinking about liking it so when you introduce anything new into the diet, I wouldn’t expect too much too fast. That would be my main advice – not to make it too much of a battle and ensure you’ve got a good dietitian who can help you.

Are stomach and bowel problems common in Noonan Syndrome?

I haven’t experienced stomach pains specifically apart from the fact that recurrent abdominal pain without an obvious cause is not uncommon in childhood in general terms. Recurrent stomach pain and cramps is quite common and I always describe it as a bit like headaches – just as some people get a lot of headaches it doesn’t mean that they’ve got an underlying disease or problem in their head. Stomach pains and stomach cramps are quite common in children and they do have a genuine experience of pain. For the overwhelming majority – 90-95% – you look after it with reassurance, simple painkillers, rubbing their tummy and usually you tend to find that it gets better. If a child’s severely unwell, has got diarrhoea or is losing weight or is becoming paler then you should, then you should definitely get medical help. It’s rare but intestinal lymphangiectasia may present with bloating, abdominal pain particularly with fatty foods and chronic diarrhoea – greasy, floating, smelly. It’s important to remember that you can have things coincidentally to Noonan’s. We have been asked if Gilbert’s Syndrome is part of Noonan Syndrome. This is a cause of jaundice and it’s relatively common but it’s likely to have been coincidental. And this is common with other symptoms and conditions.

My son, who is in his 30s, has had fertility problems as he had undescended testes which were corrected when he was a young child. Has there been research into infertility and NS?

In the original group of children with Noonan syndrome followed up from St Georges we did a small follow up study and confirmed that early surgical treatment was important and prevented the problems with infertility.

My child is low on weight 0.4 centile. Is there a link of Noonan Syndrome to low weight and what is the reason behind it?

Low weight is usually associated with reduced height – that is the child is small overall. If the weight alone is down, then the paediatrician will need to look at all the causes for poor weight gain that can affect any child.

Our daughter has recently been diagnosed with Coeliac disease, and we understand that there is a higher incidence in other syndromes such as Down’s and Turner’s. We were just wondering if that might also be the case with Noonan’s Syndrome or if you know of any research that maybe is being done into this area.

There’s an enrichment for auto immune disease across the board and celiac disease is pretty common in the general population so it wouldn’t be surprising for it to be over represented to an extent in the Noonan Syndrome population. This topic has not been systematically studied or identified in the studies known to our medical advisory group.

My understanding is that in Noonan’s puberty can be delayed in boys, but is it the same for girls? My fifteen-and-a-half year old girl is a physically fully developed young woman but hasn’t had her period yet. She is PTPN11 with a pulmonary valve stenosis.

Early studies that looked at the onset of puberty both in boys and in girls showed that puberty is delayed in both boys and girls and perhaps reaching their full potential in terms of height and development just takes that little bit longer. It is more unusual to be physically developed in terms of puberty in all other ways and to have not started periods just yet. If there is a discrepancy between the normal body development and the periods, then this should be looked at more specifically. You can get discrepancies in the process of puberty itself and there are certain orders that we anticipate in children as they move on into adulthood. When those are staggered or disordered in some way there can sometimes be some other underlying endocrine issues.

Would the growth hormone be risky for someone who has RAF1, which is high risk for HOCM, but doesn’t have it yet?

We currently do not have enough information to know whether growth hormone is riskier in certain genes, but the risk is more likely to be related to whether there is already significant HCM rather than the gene itself. We are still collecting information on this, though.

What are the chances of my child with pulmonary stenosis, who has had open heart surgery in the past, having more surgery as she gets older?

It’s very variable. It depends on the initial condition and the initial procedure performed. It’s not unusual for individuals who’ve had particularly surgery to the pulmonary valve for that valve in time to become leaky and often that does require further procedure. It’s not universal by any means and it depends on the shape and the look of the valve – the morphology of the valve and the procedure that was performed. It is well established that anyone who’s had an intervention to their pulmonary valve should have lifelong follow up. There are adult congenital heart services around the country which would provide that sort of follow up.

A lot of NS children have had open heart surgery for pulmonary stenosis. Will future developments in technique mean a less invasive treatment?

Less invasive techniques were available for more straightforward cases to open up a pulmonary valve but this “balloon” procedure didn’t work as well when the valve was very thick or abnormally formed. In these cases, surgeons often choose to go for open heart surgery as the result is likely to be better first-time round. But in many individual cases of children with NS it was possible to do the less invasive balloon dilation technique and hopefully that these techniques will improve in the future.

My son bruises very easily when he falls over and the bruises last a very long time. He’s unfortunately got both pulmonary and aortic valve problems so he’ll need an artificial valve when his heart deteriorates to a certain level and then he’ll have to go on blood thinners. What considerations would there need to be regarding his bruising issues?

There has been a fairly large study of clotting factors in children with Noonan’s which found that there were occasional issues with factor 8 clotting agent but usually these were not causing serious bleeding although they did cause bruising more easily. In rare cases of post-operative bleeding, it was relatively easy to correct that with fresh blood which did contain the clotting agent. If it did come to an operation for the child in question, the specific needs would be looked at carefully and there were options as regards blood thinners as new ones were being developed, although very few were licenced for use with children at the moment. There are artificial valves which don’t require anti-coagulation but as in most cases, it very much depended on the individual case and there would be very detailed investigation before a decision was made. There had however been several cases where Warfarin had been used with children with Noonan’s.

Our daughter has moderate pulmonary stenosis. She is nearly 3. Our son is 4 (both Noonan’s LZTR1). No detected cardiac issues. Is there any indication of the age any other cardiac issues—if they occur—might become apparent?

We are still learning about how the heart is affected in LZTR1, but it is very unlikely that any valve changes will develop if they are not present now. What can develop over time, and needs regular follow up, is hypertrophic cardiomyopathy. In most cases, we think this is often present very early on, but it can sometimes develop later in life, so we would recommend ongoing cardiac screening.

My son, 29, teacher with Tetralogy of Fallot, has a leaky pulmonary valve—is he likely to need further surgery as he gets older?

In some cases, after repair of tetralogy of Fallot, the pulmonary valve can become leaky, and this sometimes does need further surgery. It depends on the technique used for the original surgery, the degree of leakiness and the effect the leakiness has on the right side of the heart.

My son has RAF1, and he now has a moderate leaky mitral valve which was trivial and changed within 6 months to moderate along with a new leaky aortic valve. Can they self-correct or do they deteriorate, needing surgery? My son is 10 years old.

Everybody is different, and in some cases, the amount of leakiness can progress to the extent that it causes symptoms and needs surgery; in other cases, the leakiness can stay stable for many years and not cause any problems. The key is to make sure that he remains under close follow up.

My son has RAF1, and we now know we all have this same mutation. His cardiologist mainly checks for HOCM, however nobody in this family has HOCM. My son has a leaky aortic valve and a leaking mitral valve. Could the RAF1 diagnosis be incorrect, as RAF1 is associated with HOCM and not valve leakages?

Although RAF1 variants are more commonly associated with HCM, not everyone with RAF1 always has HCM, and there is a lot of overlap with other conditions, such as leaky heart valves. It is likely the RAF1 diagnosis is correct, but that is hasn’t caused HCM in the family. He should remain under follow up, though, as sometimes the HCM develops later.

My fifteen-year-old granddaughter has hypertrophic cardiomyopathy and has very heavy periods. Can she be given progesterone or the contraceptive pill to help with the period problems taking into account the hypertrophic cardiomyopathy?

This would need to be checked with her own cardiologist. It’s true that there are certain heart conditions where the oral contraceptive pill is contra-indicated and that’s because in some situations there’s an increased risk of stroke. There are some other treatments for very heavy periods that may be considered but again you may have to be guided by specialists such as a gynaecologist.

Is dysplastic aortic valve seen very often in Noonan Syndrome and what are the potential symptoms and interventions for this?

Although less common than pulmonary valve dysplasia, it is not unusual to see dysplasia of the other valves, including the aortic valve, in Noonan Syndrome. A dysplastic valve on its own shouldn’t cause any symptoms, but if it becomes narrowed or leaky, it may do, and that may require intervention (keyhole or surgical) if there is significant narrowing or leakiness.

Is it common to have an issue with a child regulating his body temperature—starting to go blue after 5 minutes swimming but so hot in bed at night he can hardly be touched?

The issue with body temperature is seen in neurological conditions such as CFC and Costello and sweating seems to be quite common in Noonan Syndrome but it does seem to diminish with age.