Random Dermatology MCQ - Beckwith-Wiedemann syndrome

A newborn infant is noted to have macroglossia, prominent abdominal wall defects (omphalocele), and significant asymmetry of the lower limbs. On physical examination, there are linear creases in the earlobes and a raised, pinkish-red, velvety plaque on the left flank. What is the most likely diagnosis and the most significant associated oncologic risk in early childhood?

A. Neurofibromatosis type 1; risk of optic pathway glioma.
B. Beckwith-Wiedemann syndrome; risk of embryonal tumors, most commonly Wilms tumor and hepatoblastoma.
C. McCune-Albright syndrome; risk of fibrous dysplasia and endocrine tumors.
D. Tuberous Sclerosis Complex; risk of subependymal giant cell astrocytoma and renal angiomyolipoma.
E. Proteus syndrome; risk of deep venous thrombosis and pulmonary embolism.

Correct Answer: B. Beckwith-Wiedemann syndrome; risk of embryonal tumors, most commonly Wilms tumor and hepatoblastoma.

Answer and Explanation

The correct answer is B. This question describes the classic triad and associated features of Beckwith-Wiedemann syndrome (BWS). The key diagnostic clues are macroglossia, abdominal wall defects (omphalocele, umbilical hernia, diastasis recti), and asymmetry/hemihypertrophy. The linear earlobe creases are a common minor feature. The "raised, pinkish-red, velvety plaque" describes a capillary malformation (nevus flammeus), particularly common on the face and neck in BWS. The most critical aspect of management is surveillance for the associated increased risk of embryonal tumors, with Wilms tumor (nephroblastoma) and hepatoblastoma being the most common.

Why the Other Options are Incorrect:

• A. Neurofibromatosis type 1: This is characterized by café-au-lait macules, axillary freckling, and neurofibromas, not the overgrowth features or midline defects seen here.

• C. McCune-Albright syndrome: This is characterized by the triad of polyostotic fibrous dysplasia, café-au-lait macules (coast of Maine), and precocious puberty. It does not involve macroglossia or omphalocele.

• D. Tuberous Sclerosis Complex: This is characterized by hypomelanotic macules, facial angiofibromas, and seizures. It is not an overgrowth syndrome with midline defects.

• E. Proteus syndrome: This is a complex, progressive overgrowth syndrome with cerebriform connective tissue nevi, but it is not typically associated with the specific triad of macroglossia, omphalocele, and capillary malformations seen in BWS.

Additional High-Yield Information for Exams:

• Genetics: BWS is caused by dysregulation of imprinted genes on chromosome 11p15.5, affecting growth promoters (e.g., IGF2) and suppressors (e.g., CDKN1C). It is a model disorder for imprinting defects.

• Dermatologic Features: Key skin findings include:

  • Capillary Malformations (Nevus Flammeus): Often midfacial or more diffuse.

  • Linear Earlobe Creases / Posterior Helical Pits: A common and characteristic minor feature.

  • Midline Facial Salmon Patch: Very common in newborns with BWS.

• Associated Conditions & Prognosis:

  • Neonatal Issues: Hypoglycemia (due to hyperinsulinism) is common and must be monitored closely in the first days of life.

  • Tumor Risk: The overall risk of embryonal tumors is ~7-10%. The peak risk is in the first 8 years of life, particularly before age 4. The most common tumors are Wilms tumor and hepatoblastoma, followed by neuroblastoma, adrenocortical carcinoma, and rhabdomyosarcoma.

  • Prognosis: With adequate management of hypoglycemia and tumor surveillance, the long-term prognosis is generally good. Overgrowth tends to plateau in mid-childhood.

• Management & Rationale:

  • Rationale: The goal is early detection and treatment of tumors to improve survival outcomes, alongside management of neonatal complications.

  • First-line Surveillance Protocol (Tumor Screening):

    • Abdominal Ultrasound: Every 3 months until age 8 years to screen for Wilms tumor and hepatoblastoma.

    • Serum Alpha-fetoprotein (AFP) Measurement: Every 3 months until age 4 years as a biomarker for hepatoblastoma.

  • Other Management: Close monitoring and treatment of neonatal hypoglycemia, management of macroglossia (speech therapy, potential surgery), and repair of abdominal wall defects.