USMLE Step 1 · Biochemistry & Genetics

Beckwith-Wiedemann syndrome vs Russell-Silver syndrome

How to tell Beckwith-Wiedemann syndrome and Russell-Silver syndrome apart when a board question makes them look alike.

Fastest separator

Beckwith-Wiedemann is 11p15 overgrowth with macroglossia/omphalocele/tumors; Russell-Silver is 11p15 growth restriction with triangular face/asymmetry.

Side by side

Beckwith-Wiedemann syndromeRussell-Silver syndrome

Key clue

Beckwith-Wiedemann causes fetal overgrowth, macroglossia, omphalocele, hemihyperplasia, neonatal hypoglycemia, and embryonal tumor risk from 11p15 imprinting abnormalities.

Russell-Silver causes intrauterine growth restriction, poor postnatal growth, triangular facies, limb/body asymmetry, and feeding difficulty from opposite 11p15 imprinting effects.

Mechanism

Increased IGF2 or reduced CDKN1C expression promotes overgrowth and tumor predisposition.

Reduced growth-promoting imprinting signals cause growth restriction and characteristic triangular facial/body asymmetry pattern.

Labs and tests

Macroglossia, omphalocele, organomegaly, hypoglycemia, and Wilms/hepatoblastoma risk support Beckwith-Wiedemann.

Small-for-gestational-age birth, poor growth, triangular face, and fifth-finger clinodactyly support Russell-Silver.

The trap

Both can involve asymmetry and imprinting, but growth direction and tumor risk separate them.

Watch it explained

60-second lessonBeckwith-Wiedemann vs Russell-Silver: 11p15 Big or Small (USMLE Step 1)

Quiz yourselfBeckwith-Wiedemann or Russell-Silver? 8-Second Genetics Pop Quiz (USMLE Step 1)

Test it now

The repair move

For imprinting growth syndromes, decide overgrowth versus growth restriction before listing features.

Try a free question

Core

A newborn has macrosomia (birth weight 4.6 kg at term), macroglossia, omphalocele, hypoglycemia (glucose 28 mg/dL) from hyperinsulinism, asymmetric left-sided hemihypertrophy, and abdominal exam reveals organomegaly (hepatomegaly, nephromegaly). Which condition is most likely?

Show answer and explanation

Answer: A. Beckwith-Wiedemann syndrome. Beckwith-Wiedemann syndrome is an 11p15 imprinting disorder (typically increased IGF2 expression or reduced CDKN1C expression) producing fetal overgrowth, macroglossia, omphalocele, neonatal hypoglycemia from islet cell hyperplasia, hemihypertrophy, and elevated risk of embryonal tumors (Wilms tumor, hepatoblastoma); surveillance with abdominal ultrasound and AFP is recommended.

Why the other choices are tempting

B. Russell-Silver syndrome is growth RESTRICTION with triangular facies and asymmetry, the opposite of overgrowth.
C. Sotos syndrome features overgrowth with dolichocephaly, learning difficulties, and NSD1 mutation, not the 11p15 imprinting pattern.
D. Simpson-Golabi-Behmel syndrome features overgrowth with polydactyly and X-linked GPC3 mutation, distinct from BWS.
E. Down syndrome features hypotonia and trisomy 21, not the overgrowth/macroglossia/omphalocele/hypoglycemia pattern.

Flashcards

Tap a card to flip it.

What clue supports Beckwith-Wiedemann syndrome?

Choose Beckwith-Wiedemann syndrome when the stem gives this pattern: Beckwith-Wiedemann causes fetal overgrowth, macroglossia, omphalocele, hemihyperplasia, neonatal hypoglycemia, and embryonal tumor risk from 11p15 imprinting abnormalities.

What clue supports Russell-Silver syndrome?

Choose Russell-Silver syndrome when the stem gives this contrasting pattern: Russell-Silver causes intrauterine growth restriction, poor postnatal growth, triangular facies, limb/body asymmetry, and feeding difficulty from opposite 11p15 imprinting effects.

Quick answers

What is the fastest way to tell Beckwith-Wiedemann syndrome from Russell-Silver syndrome?