Prader-Willi syndrome

Prader-Willi syndrome is a rare condition present from birth in which the hypothalamus does not work properly — the small part of the brain responsible for the sense of fullness, for producing growth hormone and sex hormones, and for body temperature and the sleep cycle. The whole picture follows from that: a floppy baby who cannot suck, and a few years later a child with insatiable hunger, short stature and learning difficulties. It affects roughly one in twenty thousand newborns, boys and girls equally. The main point is worth making early: with weight kept under control, life expectancy is close to normal, and most of the dangers come not from the syndrome itself but from overeating.

How the picture changes with age

The condition moves through distinct stages, and what most confuses families is the shift from one to the next. Even before birth a mother often notices that the baby moves feebly and rarely. After delivery the striking finding is unusually low muscle tone: the baby is floppy, the cry is weak, head control is poor. Sucking is almost impossible, so tube feeding is usually needed for the first weeks or months, and weight is hard to gain. This is the stage at which the syndrome is now most often picked up.

By one or two years of age the tone improves, feeding settles, and a deceptive calm arrives. Then, between the ages of two and four, weight starts to climb on its own, before appetite has changed at all. Only after that, closer to four to eight years, does hyperphagia appear: constant hunger that eating does not switch off.

This is not greed and not poor parenting: the fullness signal that normally comes from the hypothalamus simply never forms. A person can eat far more than usual and remain certain they are hungry. Hence all the behaviour around food — asking for more, bargaining, flares of temper, searching out and hiding food. These are not tantrums but the direct result of something broken in the brain, and they need to be treated as a medical problem rather than a question of discipline.

Why it happens and whether it will happen again

The cause is loss of function of a group of genes on chromosome 15, specifically in the copy inherited from the father. The mother's copy in that region is normally silent, so having it is not enough: if the paternal part is not working, the genes are switched off altogether.

There are several mechanisms behind this, and telling them apart matters because the risk of recurrence in the family depends on which one it is:

• a missing piece of the paternal chromosome — the commonest form, around two thirds of cases;
• both chromosome 15s coming from the mother with none from the father — roughly a quarter of cases;
• a fault in the mechanism that marks a chromosome as paternal or maternal — rare, but the one form that can recur;
• chromosome rearrangements, which are very uncommon.

In the first two forms the event is a matter of chance, and the likelihood of a second child with the syndrome is under one per cent. Where the marking mechanism is at fault, the risk can reach one in two. This is why the familiar reassurance that "it was a one-off and will not happen again" is not always true: it holds only once the specific mechanism has been established. It is worth discussing with a geneticist.

How the diagnosis is confirmed

Suspicion is raised by a newborn with unexplained floppiness and an inability to suck — that alone is enough to start investigating, without waiting for the other features. In older children the pointer is a combination of early obesity, developmental delay and characteristic looks: almond-shaped eyes, a narrow forehead at the temples, a thin upper lip with downturned corners, small hands and feet and, in some forms, hair and skin noticeably fairer than the rest of the family's.

The diagnosis is confirmed on a blood test. The main method is methylation analysis of the chromosome 15 region: it shows whether the paternal copy is working and picks up virtually every case whatever the mechanism. If it comes back positive, a second, more precise test identifies which of the mechanisms above was involved, and the whole conversation about the risk to future children rests on that.

A standard karyotype and routine blood tests will not show the syndrome. So if a doctor suspects Prader-Willi syndrome, what is needed is methylation analysis specifically, not "genetic testing" in general.

Food and weight: the heart of the care

This is the hardest and the most important part, and it has nothing to do with the child's willpower. Every measure has the same aim: to take away an impossible task, that of limiting oneself around food.

Calorie needs here are markedly lower than usual: there is less muscle, less activity and a thriftier metabolism. So the plan is drawn up by a dietitian rather than calculated as it would be for any child of that age. It makes sense to start with the first solid foods, long before the increased appetite appears: a habit of routine and of no sweets settles far more easily while nobody has to fight for it.

In practice families build predictability around food. It rests on three things: mealtimes are fixed and known in advance; there are no second helpings, and that is not renegotiated each time; what has been promised always happens. A child finds this calmer than a kind but shifting regime, because uncertainty around food is more distressing than the rule itself. Hence the practical measures: locks on kitchen cupboards and the fridge, closed bins, no free access to food between meals. Relatives, family friends, carers and teachers all need to know, or one "harmless" sweet undoes months of work. And food is never used as a reward.

Activity helps but has to be adapted: there is less energy, and long sessions end in refusal. Several short bursts through the day work better, as do individual activities rather than team ones. No medicine yet reliably reduces appetite in this syndrome, and weight-loss surgery is not recommended: it demands strict self-restraint afterwards, and that is out of reach here.

Growth, hormones and puberty

The hypothalamus governs several hormone systems at once, so there is more than one problem to manage.

Little growth hormone is produced: children are noticeably shorter than their peers by the age of two, and the pubertal growth spurt never comes. Treatment with synthetic growth hormone is now standard and starts early, usually in the first or second year of life. It gives more than height: muscle mass rises and fat falls, the child becomes stronger and more mobile, and motor and language development move along better. There is an important safety caveat: breathing during sleep is always assessed before starting and while on treatment, because growth hormone can worsen pauses in breathing, and treatment is paused during a severe chest infection.

The sex glands work poorly. Undescended testicles are common in boys and are usually corrected surgically in the first years of life. Puberty is late and generally incomplete: young men have little facial and body hair; in girls periods start late, are scanty and irregular, and sometimes never begin. Hormone replacement is considered case by case; in girls it also matters for bone, since without sex hormones osteoporosis appears early. In boys the question is trickier: testosterone helps muscle and maturation but can sometimes sharpen behavioural difficulties. Pregnancy is virtually unknown in this syndrome, but a sexual life is possible and contraception does need discussing.

Learning, behaviour and sleep

Learning difficulties are usually mild or moderate. A child sits and walks later, speech comes late, and some sounds are unclear. Even so, most have real strengths: good long-term memory and a talent for fitting and finding tasks such as jigsaws, puzzles and word searches. Most attend mainstream school with support.

Behavioural difficulties sharpen with unexpected change, being rushed, pressure, noisy surroundings and anything to do with food. What helps is a predictable routine, warning of changes in advance, plenty of time to get ready, and a calm adult response. During an outburst it is better to name the feeling out loud, move the person somewhere quiet and wait it out, leaving any discussion of what happened until several hours later. Skin picking is common, leaving sores on the face and forearms that will not heal: short nails, dressings and covering clothing all help, and persistent picking responds to psychological therapy. Medication is considered only for serious damage, since the side effects are not trivial.

Sleep is disturbed in almost everyone: daytime sleepiness sits alongside waking at night. Pauses in breathing during sleep are looked for specifically, since both kinds occur here — the kind caused by the airway closing and the kind caused by a fault in the breathing centre. This is no small matter: untreated pauses worsen daytime sleepiness, that reduces activity, activity affects weight, and the circle closes. Finally, in some people — more often in the form with two maternal chromosomes — psychosis develops in adolescence or adult life. A sudden, out-of-character change in behaviour means contacting the medical team straight away.

What makes the syndrome dangerous

In itself it does not shorten life. The danger lies in its consequences, and almost all of them are preventable:

• obesity and everything that travels with it — type 2 diabetes, high blood pressure, heart failure, blood clots, leg ulcers;
• pauses in breathing during sleep and poor ventilation of the lungs from weak muscles and excess weight;
• blunting of both the vomiting and the pain signal: appendicitis, a fracture or a serious infection can pass almost without complaint;
• over-distension and rupture of the stomach — a rare complication but one particular to this syndrome, following an episode of binge eating;
• choking: food is swallowed fast and poorly chewed, so carers should learn how to deal with an obstructed airway;
• curvature of the spine, which is monitored throughout growth;
• tooth decay from thick, sticky saliva, calling for more frequent dental visits;
• osteoporosis in adult life;
• unstable body temperature and unexpected reactions to anaesthesia, which the anaesthetist must be told about in advance.

The pain threshold deserves a separate mention. If someone with Prader-Willi syndrome complains of pain, it almost always means the pain is severe. Such complaints are never left until tomorrow.

When urgent help is needed

Call an ambulance (in Spain, Italy, Portugal, Poland and Ukraine that is 112) if there is:

• vomiting or abdominal pain, especially in someone who does not normally vomit or complain of pain;
• a swollen, hard, tender abdomen after an episode of binge eating;
• choking, an inability to cough, blue lips;
• sudden breathlessness, confusion, unusual drowsiness;
• a sudden, out-of-character change in behaviour with agitation and bewilderment.

The first two point to possible rupture of the stomach, a situation counted in hours. Tell the medical staff the diagnosis immediately: without it, vomiting and abdominal pain are easily mistaken for ordinary food poisoning and time is lost.

See a doctor the same day for a temperature with listlessness, skin wounds that will not heal or have become inflamed, new snoring with pauses in breathing, or a sharp change in weight in either direction.

Online consultation

Looking after Prader-Willi syndrome is teamwork: paediatrician, endocrinologist, dietitian, geneticist, speech and language therapist, behaviour specialist, orthopaedic surgeon. An online appointment covers well everything that does not require travelling: going through results and understanding which mechanism was found and what it means for the family; checking that growth hormone treatment is on track and when the sleep study is due again; rebuilding the eating routine when a child moves into a new stage or a new school; talking through what to do about outbursts and skin picking.

Have ready the genetic report, letters from specialists, a list of medicines and doses, growth and weight charts, and a description of an ordinary day: what the child eats and when, how they sleep, what triggers a meltdown. It is also worth asking about a plan for days of illness and about what the medical team must be told if an operation ever becomes necessary.

This material is for information only and does not replace medical advice.