Weight Loss with Myhre Syndrome in South Africa

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.

Understanding Myhre Syndrome: The Features That Affect Weight

The Obesity Component

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.

Joint Stiffness (Arthropathy)

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:

• Severely limits range of motion in hips, knees, shoulders, and spine
• Makes conventional exercise (running, cycling, gym) difficult or impossible
• Does not respond well to standard anti-inflammatory medications
• May progress with age in some patients

LAPS Syndrome and Fibrosis

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:

• Exercise capacity (reduced if airway is narrow)
• Food choices (dysphagia requires texture modification)
• Energy expenditure (reduced physical activity)

Hearing Loss

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.

Why Losing Weight Matters — and Why It Is Hard

For people with Myhre syndrome, losing weight is particularly important because:

• Excess body weight worsens cardiovascular risk — already elevated due to the fibrotic process affecting the heart and great vessels
• Obesity increases mechanical load on already-stiff joints — a vicious cycle where stiffness reduces activity, activity reduction causes weight gain, and weight gain worsens joint stress
• Visceral fat independently drives inflammation, potentially worsening the TGF-beta dysregulation that underlies the syndrome
• Better weight control improves breathing capacity — especially relevant where airway stenosis is present

But it is also genuinely hard because:

• Joint stiffness severely limits the exercise types available
• Short stature means lower total calorie requirements — less "room" for error
• Some patients have intellectual disability that complicates independent dietary decision-making
• Swallowing difficulties (if present) limit food variety and texture

Dietary Approach: Anti-Inflammatory, Anti-Fibrotic Foundation

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.

Foods to Emphasise

Foods to Reduce

• Ultra-processed food: Chips, fast food, instant noodles — pro-inflammatory and calorie-dense
• Refined sugar and sweet drinks: Drive visceral fat accumulation particularly in truncal obesity patterns
• Excess red meat: Pro-inflammatory at high intakes; limit to 2–3 portions per week maximum
• Biltong and processed meats: High sodium increases cardiovascular risk — limit strictly
• Alcohol: Worsens fibrosis in multiple organ systems; avoid or minimise entirely
• High-sodium foods: Aromat, soy sauce, tinned soups — worsen cardiovascular risk and fluid retention

Portion Control: The Short Stature Factor

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.

Exercise: Working Around Stiff Joints

Standard exercise advice is largely inapplicable for people with Myhre syndrome arthropathy. Here is what can work:

Hydrotherapy / Aqua Aerobics

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.

Seated and Chair-Based Exercise

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.

Walking (Where Joint Range Allows)

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.

Breathing Exercises

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.

Medical Monitoring for Weight Management

Navigating Rare Disease in South Africa

With fewer than 200 known cases globally, you are unlikely to find a Myhre syndrome specialist in South Africa. However:

• Clinical geneticists at academic hospitals (Charlotte Maxeke, Groote Schuur, Steve Biko, Chris Hani Baragwanath) are your best starting point for coordination of care
• Rare Disease South Africa (RDSA) at rarediseasessa.org connects families with similar conditions and lobbies for medical aid coverage
• International expert consultation: Many Myhre syndrome cases are managed in collaboration with European centres — your geneticist can facilitate telemedicine consultations
• Medical aid coverage: Most rare diseases qualify for Prescribed Minimum Benefit (PMB) status under chronic disease — confirm with your scheme

Key Takeaways

• Myhre syndrome (SMAD4 mutation) causes truncal obesity, stiff joints, and systemic fibrosis — all of which complicate standard weight management advice
• An anti-inflammatory Mediterranean-style diet is the best dietary foundation — focus on oily fish, colourful vegetables, legumes, and olive oil
• Avoid alcohol, ultra-processed food, excess sodium, and refined sugar
• Exercise must work around joint stiffness — hydrotherapy, chair-based exercise, and gentle walking are priorities
• Get cardiac, airway, and joint assessments before starting an exercise programme
• Short stature means lower calorie needs — portion management is critical; use smaller plates
• Clinical geneticist + rare disease-experienced dietitian is your ideal care team