Rare genetic diseases of obesity present with a variety of clinical characteristics such as hypothyroidism, hypogonadism, renal abnormalities, and developmental delays.1
However, 2 hallmark symptoms common to many of these rare genetic diseases help separate them from more common forms of obesity:1,7

  • Early-onset, severe obesity
  • Hyperphagia

More information on Hallmark Symptoms of Bardet-Biedl syndrome (BBS)

What to look for

Early-onset, severe obesity:

Some forms of obesity are caused by genetic variants in a key neurosignaling pathway in the hypothalamus responsible for regulating hunger (the MC4R pathway).1,2

A BMI curve well above reference percentiles as shown in the graph may indicate an underlying rare genetic disease of obesity.22

BMI curves indicating underlying rare genetic diseases of obesity

Hyperphagia:

These patients present with defining behaviors, including:23,24

Heightened and prolonged hunger

Heightened and prolonged hunger

Longer time to reach satiety

Longer time to reach satiety

Shorter duration of satiety

Shorter duration of satiety

Severe preoccupation with food

Severe preoccupation with food

Excessive food-seeking behaviors

Excessive food-seeking behaviors (night eating, stealing food, foraging for food in trash)

Significant distress and inappropriate response if denied food

Significant distress and inappropriate response if denied food

Searching for answers

“Joshua was born a normal weight but continued gaining weight right from the start. He gained 6 pounds between a 4- and a 6-month checkup. He is just continually feeling hungry.”

Molly

Mom to Joshua, living with Bardet-Biedl Syndrome

If you suspect a patient may be experiencing hyperphagia

Below are some common questions to ask:

For patients

Sleep
Do you wake up asking or searching for food during the night?
If so, how does this affect your sleep?

Mood
Do you ever feel hungry after you just ate?
Do you ever feel stressed out due to hunger, or worry about food?

School/work
How does hunger impact your ability to concentrate at school or work?

Recreational activities
Has hunger ever impacted your ability to participate in recreational activities?

Relationships with family/friends
How does hunger impact your relationships with family or friends?

For caregivers

Sleep
Does the patient wake up asking or searching for food during the night?
How does this affect the patient’s sleep?
How does this affect you?

Mood
How does hunger impact the patient’s mood?
Does the patient feel stressed due to food?
How does this affect you getting things done at home or at work?

School/work
Does hunger impact the patient’s ability to concentrate at school or work? How?

Recreational activities
Does hunger impact the patient’s ability to participate in recreational activities?

Relationships with family/friends
How does hunger impact the patient’s relationships with other family members/friends?
Have you had any uncomfortable or strained interactions with your family or friends due to your child’s hunger?

Diagnosing rare genetic diseases of obesity

Some rare genetic diseases of obesity can be diagnosed clinically, while genetic testing can aid in the diagnosis of others.7,8

Clinically diagnosed (Syndromic)

Certain syndromic rare genetic diseases of obesity can be diagnosed clinically based on specific clinical characteristics. In addition to early-onset, severe obesity and hyperphagia, these diseases can also present with visual impairment, cognitive impairment, postaxial polydactyly, renal anomalies, hypogonadism, or other possible clinical characteristics.1

Explore diagnosis of:

Bardet-Biedl syndrome

Alström syndrome

Genetic testing may also help confirm a suspected clinical diagnosis.

Genetically identifiable (Non-Syndromic)

For non-syndromic rare genetic diseases of obesity, genetic testing can help you and your patients better understand a primary cause of their obesity by identifying relevant genetic variants.

This knowledge can inform:

  • Possible diagnosis
  • Appropriate disease management options
  • Potential eligibility for clinical studies

Patients and families often gain a great sense of relief in knowing there is an underlying cause of their obesity unrelated to environmental and lifestyle factors.

Explore more about:

POMC deficiency

LEPR deficiency

PCSK1 deficiency

SRC1 Deficiency

SH2B1 Deficiency

Genetic testing may lead to diagnosis, options and relief
Genetic testing may lead to diagnosis, options and relief

“We suggest genetic testing in patients with extreme early-onset obesity (before 5 years of age) and that have clinical features of genetic obesity syndromes (in particular extreme hyperphagia) and/or a family history of extreme obesity.”7

Endocrine Society Icon

“Genetic testing recommended with clinical features such as extreme hyperphagia and/or family history of extreme obesity.”8

Obesity Medicine Association Icon
Uncovering Rare Obesity logo Uncovering Rare Obesity logo

Genetic testing program

Uncovering Rare Obesity® is a no-charge genetic testing program for rare genetic diseases of obesity.

Rhythm Pharmaceuticals covers the cost of the test and provides sample collection kits. Patients are responsible for any office visit, sample collection, or other costs.

Explore testing opportunities

LEPR=leptin receptor; MC4R=melanocortin-4 receptor; PCSK1=proprotein convertase subtilisin/kexin type 1; POMC=proopiomelanocortin; SH2B1=SH2B adaptor protein 1; SRC1=steroid receptor coactivator-1.

  • References

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