Myhre syndrome is so rare that fewer than 200 confirmed cases have been described in the medical literature worldwide. It is caused by gain-of-function mutations in the SMAD4 gene — specifically in the MH2 domain. SMAD4 is a critical mediator of TGF-beta signalling, a pathway that controls tissue growth, repair, and inflammation. When SMAD4 is dysregulated, it drives excessive tissue fibrosis (scarring) throughout the body.
The condition was first described by Norwegian paediatrician Lars Myhre in 1981. It is also called LAPS syndrome (laryngotracheal stenosis, arthropathy, prognathism, and short stature) — reflecting its most serious manifestations. Because it is so rare, most South African GPs and dietitians will never have encountered it. This guide bridges that knowledge gap.
This article is for educational purposes only. Always work with a specialist familiar with your condition — ideally a clinical geneticist and a dietitian with rare disease experience.
Truncal obesity — excess fat around the abdomen and torso with relatively thin limbs — is a consistent feature of Myhre syndrome. It appears to be partly driven by dysregulated TGF-beta/SMAD4 signalling affecting adipose tissue development and fat distribution, and partly by reduced physical activity due to joint stiffness and short stature. The result is a body shape resembling central obesity seen in Cushing's syndrome or metabolic syndrome.
One of the hallmark features is progressive joint stiffness. Unlike inflammatory arthritis (where the joint is inflamed and painful), Myhre syndrome arthropathy is fibrotic — the connective tissue around joints becomes thickened and stiff due to excess collagen deposition. This:
LAPS syndrome is the most serious complication. Subglottic or tracheal stenosis (narrowing of the airway) can develop, causing breathing difficulties. Gastrointestinal fibrosis can affect swallowing and gut motility. These complications must be monitored regularly and can affect:
Sensorineural hearing loss is present in most individuals with Myhre syndrome. While not directly affecting weight, it impacts quality of life, social engagement, and the ability to follow exercise class instructions — practical points worth noting.
For people with Myhre syndrome, losing weight is particularly important because:
But it is also genuinely hard because:
No Myhre-syndrome-specific diet exists — the evidence base is simply too thin for a condition this rare. However, given the underlying TGF-beta dysregulation driving fibrosis and the cardiovascular risk profile, a Mediterranean-style anti-inflammatory diet makes strong biological sense.
| Category | Why | SA Examples |
|---|---|---|
| Oily fish (omega-3) | Anti-inflammatory; counters TGF-beta excess; cardioprotective | Pilchards, snoek, mackerel, fresh hake |
| Colourful vegetables | Antioxidants reduce oxidative stress that worsens fibrosis | Spinach, butternut, peppers, broccoli, beetroot |
| Legumes | Plant protein, fibre, low GI — supports satiety at low calorie cost | Lentils, borlotti beans, speckled beans, chickpeas |
| Olive oil | Oleocanthal has anti-inflammatory properties; healthy fat | Extra virgin olive oil for cooking and dressing |
| Berries and citrus | Quercetin and vitamin C have anti-fibrotic properties in research | Strawberries, oranges, naartjies, blueberries |
| Whole grains | Low-GI energy; fibre; reduces visceral fat | Oats, brown rice, whole wheat bread, barley |
Average-height adults require roughly 2 000–2 500 kcal/day to maintain weight. Many adults with Myhre syndrome have significantly shorter stature, meaning maintenance energy requirements may be 1 400–1 700 kcal/day. This leaves a very small margin for a weight loss deficit without feeling excessively deprived. Work with a dietitian to calculate your individual requirements precisely.
Standard exercise advice is largely inapplicable for people with Myhre syndrome arthropathy. Here is what can work:
Water buoyancy dramatically reduces joint load while allowing meaningful cardiovascular exercise. Heated pools (32–34 °C) also reduce joint stiffness. This is the single best exercise option for most people with Myhre syndrome. Many municipal pools in Johannesburg, Cape Town, and Durban offer hydrotherapy or aqua aerobics sessions.
Chair yoga, seated resistance band exercises, and upper body ergometer work can all be performed without loading stiff lower limb joints. YouTube has extensive chair exercise resources suitable for limited mobility.
Short, frequent walks — even 10–15 minutes after meals — aid glucose metabolism and calorie expenditure without the high joint loading of longer sessions. Flat surfaces are preferred; avoid hills that require deep knee bend.
For those with mild airway involvement, supervised respiratory physiotherapy and breathing exercises can improve lung function and exercise tolerance. This is a prerequisite before starting aerobic exercise if there is any known tracheal stenosis.
| Check | Frequency | Why |
|---|---|---|
| Cardiac echo + ECG | Annually | Pericardial fibrosis and valve changes are documented in Myhre syndrome |
| Airway assessment (ENT/pulmonology) | Annually or if symptoms change | Laryngotracheal stenosis can be silent until severe |
| Blood pressure | Every 6 months | Cardiovascular risk elevated; hypertension common |
| Fasting glucose and lipids | Annually | Truncal obesity pattern associated with insulin resistance and dyslipidaemia |
| Joint range of motion assessment | Annually (physiotherapy) | Track progression; adjust exercise as range changes |
With fewer than 200 known cases globally, you are unlikely to find a Myhre syndrome specialist in South Africa. However: