Pediatric Obesity Etiology Screener

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name: pediatric-obesity-etiology-screener
description: Screen a child with obesity for red flags suggesting monogenic, syndromic, or secondary endocrine causes — distinguishing atypical from typical exogenous obesity. Trigger when a clinician asks whether obesity could be genetic or hormonal, suspects Prader-Willi syndrome, Cushing disease, hypothyroidism, ROHHAD, Bardet-Biedl syndrome, leptin deficiency, or craniopharyngioma, or when a child has early-onset severe obesity, short stature with obesity, hyperphagia, hypotonia, dysmorphic features, or developmental delay with weight gain.
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# Pediatric Obesity: Atypical Etiology Screener

Distinguish typical exogenous obesity from monogenic, syndromic, or secondary endocrine causes using a structured red flag screen.

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## Step 1 — Establish the Typical Baseline

**Typical exogenous obesity looks like this — if ALL present, atypical cause is less likely:**

| Feature | Typical Exogenous Obesity |
|---|---|
| Onset | Gradual, often after age 5 |
| Height | Normal to **tall** for age (advanced skeletal maturation) |
| Development | Normal milestones |
| Appetite | Increased but not insatiable |
| Dysmorphic features | Absent |
| Family history | Usually positive for obesity |

> ⚠️ If **any** feature deviates from the above, proceed through the red flag screen below.

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## Step 2 — Red Flag Screen

Work through each domain. One or more flags = investigate further.

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### 🔴 Domain 1: Age and Onset of Obesity

| Red Flag | Suspect |
|---|---|
| Obesity onset **before age 2–5 years**, especially severe | Monogenic obesity: leptin deficiency, leptin receptor deficiency, POMC deficiency, MC4R mutation |
| **Abrupt, rapid** weight gain at any age | Hypothalamic lesion (craniopharyngioma), ROHHAD/ROHHADNET syndrome, new-onset endocrine disorder |

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### 🔴 Domain 2: Growth Pattern

| Red Flag | Suspect |
|---|---|
| **Short stature** in a child with obesity | Endocrine cause (Cushing disease, hypothyroidism, GH deficiency) or genetic syndrome |
| **Declining height velocity** despite obesity | Endocrine disorder — especially Cushing or hypothyroidism |

> 📏 **Key rule:** Exogenous obesity accelerates growth. A child with obesity who is short or growing slowly almost certainly has a non-exogenous cause. This is one of the most important red flags in paediatric practice.

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### 🔴 Domain 3: Appetite

| Red Flag | Suspect |
|---|---|
| **Marked, uncontrollable hyperphagia** — insatiable hunger, food-seeking behaviour, food obsession | Monogenic obesity (leptin deficiency, POMC deficiency, MC4R), Prader-Willi syndrome, hypothalamic obesity |

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### 🔴 Domain 4: Development and Neurology

| Red Flag | Suspect |
|---|---|
| **Developmental delay or intellectual disability** | Syndromic causes: Prader-Willi, Bardet-Biedl, Cohen syndrome |
| **Hypotonia in infancy** followed by hyperphagia and rapid weight gain in early childhood | Prader-Willi syndrome (classic presentation) |
| **Headaches, nausea, vision changes, nystagmus** | Craniopharyngioma or other hypothalamic-pituitary tumour |
| Autonomic dysregulation, hypoventilation | ROHHAD/ROHHADNET syndrome |

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### 🔴 Domain 5: Physical and Genitourinary Findings

| Red Flag | Suspect |
|---|---|
| **Dysmorphic features** — unusual facies, small hands/feet, polydactyly | Bardet-Biedl syndrome (polydactyly), Prader-Willi syndrome, other chromosomal syndromes |
| **Delayed or absent puberty**, undescended testes, micropenis, small testes | Prader-Willi syndrome, Bardet-Biedl syndrome, leptin deficiency, endocrine cause |
| **Precocious puberty** | CNS lesion, ROHHAD syndrome |
| **Pale skin with red hair** (in White individuals) | POMC deficiency (classic triad: early-onset obesity + red hair + adrenal insufficiency) |
| **Retinal pigmentation, visual impairment, or deafness** | Bardet-Biedl syndrome, Alström syndrome |
| **Dry/coarse hair, constipation, cold intolerance, bradycardia** | Hypothyroidism |
| **Violaceous striae, interscapular fat pad (buffalo hump), moon facies, proximal myopathy, hypertension** | Cushing syndrome / Cushing disease |
| **Polydipsia, polyuria** | Diabetes insipidus (hypothalamic cause), or new-onset T1DM masking with insulin-driven weight gain |

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## Step 3 — Triage by Flag Pattern

| Flags Present | Most Likely Cause | Urgency |
|---|---|---|
| Onset < 2 yrs + severe hyperphagia, no dysmorphia | Monogenic obesity (leptin, POMC, MC4R) | Elective referral to paediatric endocrinology/genetics |
| Neonatal hypotonia + later hyperphagia + developmental delay + hypogonadism + small hands/feet | **Prader-Willi syndrome** | Genetic testing (methylation studies) — confirm urgently |
| Polydactyly + retinal dystrophy + intellectual disability + hypogonadism | **Bardet-Biedl syndrome** | Genetics + ophthalmology referral |
| Short stature + obesity + violaceous striae + buffalo hump | **Cushing syndrome** | Endocrine workup (24h UFC, midnight salivary cortisol, low-dose DST) |
| Short stature + obesity + dry skin + constipation + bradycardia | **Hypothyroidism** | TSH + Free T4 — urgent |
| GH deficiency signs + short stature + obesity | **GH deficiency** | IGF-1, IGFBP-3, GH stimulation testing |
| Rapid-onset obesity + autonomic dysfunction + hypoventilation | **ROHHAD/ROHHADNET** | Urgent paediatric neurology/respirology |
| Headaches + visual changes + rapid weight gain | **Craniopharyngioma** | Urgent MRI brain/pituitary |
| Red hair + early-onset obesity + adrenal insufficiency signs | **POMC deficiency** | Urgent cortisol, ACTH, genetics |
| Visual impairment + sensorineural deafness + obesity | **Alström syndrome** | Genetics + ophthalmology |

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## Step 4 — Initial Investigations to Order

Based on red flags identified, order as indicated:

**Endocrine screen (if short stature, striae, or growth deceleration):**
- TSH, Free T4
- 24-hour urinary free cortisol or midnight salivary cortisol
- Morning cortisol + ACTH
- IGF-1, IGFBP-3

**Genetic/syndromic workup:**
- Chromosomal microarray (for dysmorphic features or intellectual disability)
- Prader-Willi methylation studies (if clinical features present)
- Specific gene panel (leptin, leptin receptor, POMC, MC4R, BBS genes) via genetics referral

**Neuroimaging:**
- MRI brain and pituitary (if headaches, visual symptoms, rapid-onset hypothalamic obesity, or ROHHAD suspected)

**Ophthalmology:**
- Fundoscopy / ERG (if Bardet-Biedl or Alström suspected)

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## Clinical Guardrails

- **Short stature + obesity = endocrine cause until proven otherwise.** Do not attribute growth failure to obesity alone.
- **POMC deficiency is rare but treatable** — setmelanotide (MC4R agonist) is approved; early identification matters.
- **Leptin deficiency** is also treatable with recombinant leptin — do not miss it in severe early-onset obesity.
- **Prader-Willi:** Genetic confirmation should precede growth hormone therapy (standard of care in PWS); confirm before starting.
- **Cushing in children is almost always ACTH-dependent (Cushing disease)** — screen carefully; obesity + hypertension + poor linear growth is the triad.
- **ROHHAD is life-threatening** — hypoventilation can cause sudden death; refer urgently if suspected.
- **Monogenic obesity does not exclude pharmacotherapy** — GLP-1RAs and setmelanotide may still be appropriate after diagnosis.

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## Source

Clinical content synthesised from:
- CMAJ 2025 Clinical Practice Guideline: *Managing obesity in children.* Ball GDC et al. doi: [10.1503/cmaj.241456](https://doi.org/10.1503/cmaj.241456)
- Choquet H, Meyre D. *Genetics of Obesity: What have we Learned?* Curr Genomics. 2011.
- Forsythe E, Beales PL. *Bardet-Biedl Syndrome.* Eur J Hum Genet. 2013.
- Styne DM et al. *Pediatric Obesity — Assessment, Treatment, and Prevention.* JCEM 2017.