Exomphalos-macroglossia-gigantism syndrome

Exomphalos-macroglossia-gigantism syndrome, also known as Beckwith-Wiedemann syndrome (BWS), is a genetic disorder that is present at birth and is characterized by a triad of distinctive clinical features: exomphalos (abdominal wall defect), macroglossia (enlarged tongue), and gigantism (overgrowth). This syndrome is a complex condition involving various systems of the body and has implications for growth, development, and an increased risk for certain types of tumors.

Etiology and Genetics

Beckwith-Wiedemann syndrome is primarily caused by changes in the regulation of gene expression in a region of chromosome 11 known as 11p15.5. This region contains several genes that are critical for growth and development, including IGF2 (insulin-like growth factor 2) and H19. The syndrome can result from various genetic mechanisms, including changes in DNA methylation, paternal uniparental disomy (UPD), or mutations in specific genes such as CDKN1C. It is often sporadic, but familial cases have been reported, suggesting a genetic predisposition in some instances.

Clinical Features

The hallmark features of Beckwith-Wiedemann syndrome include:

• Exomphalos: A defect in the abdominal wall where the intestines are covered by a thin layer of tissue and protrude outside the abdomen.
• Macroglossia: An abnormally large tongue, which can cause difficulties with feeding, speech, and breathing.
• Gigantism: Excessive growth and increased height and weight above the 97th percentile for the child's age and sex.

Other associated features may include:

• Hemihyperplasia (asymmetric body growth)
• Ear creases or pits
• Neonatal hypoglycemia (low blood sugar levels in newborns)
• An increased risk of developing certain types of tumors, such as Wilms tumor, hepatoblastoma, and neuroblastoma.

Diagnosis

Diagnosis of Beckwith-Wiedemann syndrome is based on clinical criteria and can be confirmed with genetic testing. Prenatal diagnosis is possible through ultrasound findings and molecular genetic testing.

Management

Management of Beckwith-Wiedemann syndrome is multidisciplinary and may involve:

• Monitoring for tumor development through regular abdominal ultrasounds and blood tests.
• Management of hypoglycemia, often requiring frequent feedings or intravenous glucose solutions.
• Surgical interventions for abdominal wall defects and macroglossia.
• Supportive therapies for developmental delays and speech or feeding difficulties.

Prognosis

The prognosis for individuals with Beckwith-Wiedemann syndrome varies depending on the severity of symptoms and the presence of tumors. With appropriate management, the life expectancy can be normal, although individuals may require ongoing monitoring and treatment for associated conditions.