Question

An infant presents with hemihypertrophy, an umbilical hernia, and has an increased risk of developing Wilms tumor. What is the most likely diagnosis?

• A. Beckwith-Wiedemann syndrome
• B. Denys-Drash syndrome
• C. Perlman syndrome
• D. Hypothyroidism

Hint:

Beckwith-Wiedemann Syndrome (BWS) Highlights:
- Triad: Macrosomia/Hemihypertrophy + Macroglossia + Omphalocele/Umbilical hernia.
- Neonatal metabolic issue: Hyperinsulinemic hypoglycemia.
- Associated tumors: Wilms tumor + Hepatoblastoma.
- Genetic locus: Chromosome 11p15.5 imprinting center defect.

Answer 1

The Correct Option is A

Concept:
Beckwith-Wiedemann Syndrome (BWS) is a classic congenital genomic imprinting disorder involving the chromosome 11p15.5 region, which regulates fetal and post-natal growth through genes such as $IGF2$, $H19$, and $CDKN1C$.
It represents the most common pediatric overgrowth syndrome and is strongly associated with an elevated predisposition to specific embryonal pediatric neoplasms.
Explanation:
• The hallmark clinical triad of Beckwith-Wiedemann syndrome comprises:
1. Macrosomia Overgrowth (with somatic hemihypertrophy/hemihyperplasia).
2. Macroglossia (large tongue causing feeding difficulties and upper airway compromise).
3. Anterior abdominal wall defects (such as umbilical hernia, omphalocele, or diastasis recti).

• Additional classic phenotypic features include neonatal hypoglycemia (due to pancreatic islet cell hyperplasia and hyperinsulinism), characteristic ear creases/helical pits, and organomegaly (nephromegaly, hepatomegaly, and adrenomegaly).

• Children with BWS have a 7.5% to 10% lifetime risk of developing childhood embryonal tumors, most notably Wilms tumor (nephroblastoma) and hepatoblastoma, followed by adrenocortical carcinoma and neuroblastoma.

• Routine tumor surveillance in BWS involves abdominal ultrasonography every 3 months until age 8 years (for Wilms tumor) and serum alpha-fetoprotein (AFP) screening every 3 months until age 4 years (for hepatoblastoma).

• Denys-Drash syndrome is characterized by the triad of Wilms tumor, diffuse mesangial sclerosis (causing early nephrotic syndrome and renal failure), and male pseudohermaphroditism ($WT1$ mutation), but lacks hemihypertrophy and macroglossia.

• Perlman syndrome is an autosomal recessive overgrowth syndrome with fetal gigantism, facial dysmorphism, renal dysplasia, and high Wilms tumor risk ($DIS3L2$ mutation), but does not feature classic hemihypertrophy.
Final Answer:
The clinical triad of hemihypertrophy, anterior abdominal wall defect (umbilical hernia), and high risk for Wilms tumor is diagnostic of Beckwith-Wiedemann syndrome.