Exomphalos-Macroglossia-Gigantism Syndrome, also known as neonatal hypoglycemia-macroglossia-visceromegaly-omphalocele syndrome or neonatal hypoglycemia with visceromegaly-macroglossia-cerebral syndrome, was first described by Beckwith in 1963, hence referred to as Beckwith syndrome. In 1964, Weidemann reported three siblings affected by the same condition, leading to its alternative name, Beckwith-Weidemann syndrome.

bubble_chart Etiology

The etiology of this disease is unknown. It is a congenital genetic disorder inherited in an autosomal recessive manner, often occurring in the offspring of consanguineous marriages. The pathogenesis remains unclear. Some researchers measured plasma insulin levels in four affected children and found significantly elevated concentrations, suggesting that hyperfunction of proliferated pancreatic β-cells leading to hyperinsulinemia is the basis for hypoglycemia. Others propose that relative insufficiency of pancreatic α-cell function and impaired glycogenolysis may also contribute to hypoglycemic episodes.

bubble_chart Pathological Changes

Pathological changes include pancreatic hypertrophy in all cases, hyperplasia of pancreatic β-cells, and electron microscopy reveals an increase in β-cell secretory granules.

bubble_chart Clinical Manifestations

Clinically, the disease can occur in both males and females. Infants exhibit numerous deformities at birth, with a significantly larger physique compared to typical newborns, a large tongue that often protrudes from the mouth, clumsy movements, impaired normal sucking and occlusion, and a mouth that does not enlarge. Abdominal distension with omphalocele or umbilical hernia is common. Within the first month after birth, infants may appear emaciated, with markedly reduced subcutaneous fat, but growth accelerates in subsequent months, sometimes approaching gigantism. By around one year of age, symptoms include unclear speech, language disorders, and a protruding jaw. Hypoglycemic episodes are a prominent symptom, occurring within hours after birth and recurring frequently. Severe cases may present with spasms and loss of consciousness, with blood glucose levels dropping below 1.1 mmol/L. Hypoglycemic episodes are most frequent in the first month after birth, gradually decreasing thereafter, and typically cease by 3–4 months, though some may persist until 2–3 years of age. Some infants may not experience hypoglycemia at all. Statistics show hypoglycemia occurs in approximately 33–50% of cases. Visceromegaly is also common, with disproportionate enlargement of organs such as the liver, kidneys, pancreas, and heart. Other features may include facial flame nevi, auricle deformities, midface hypoplasia, diaphragmatic defects, clitoromegaly, cryptorchidism, intestinal volvulus, maternal polyhydramnios, and macrosomia. Infants often exhibit grade I intellectual disability and microcephaly. Those who survive into childhood may develop hemihypertrophy and are prone to malignant tumors, such as adrenal adenomas, Wilms tumor, seminomas, hepatoblastomas, and abdominal tumors.

Laboratory tests revealed decreased blood glucose levels, with plasma cortisol and thyroxine (T₄) measurements within normal ranges. Intravenous glucose infusion in the child could stimulate increased insulin secretion. The use of glucagon and D₈₆₀ tests both induced significant and prolonged insulin secretion, thereby triggering hypoglycemic episodes. Urinalysis was normal. Peripheral erythrocytosis was observed.

bubble_chart Treatment Measures

The treatment for hypoglycemia involves intravenous glucose injection or infusion, which alone is often insufficient to maintain normal blood sugar levels and only provides a temporary increase. Combining corticosteroids can help stabilize blood sugar. Medication should continue until hypoglycemic episodes cease, typically lasting 1 to 3 months. During treatment, frequent feeding with milk and solid foods is recommended to reduce hypoglycemic episodes. For umbilical hernias, plastic surgery may be performed.

bubble_chart Prognosis

The prognosis of this disease is poor. Except for mild cases, survival is extremely rare, and death typically occurs within 1 to 4 months.