Beckwith Wiedemann Syndrome – Complications and Prevention.

Definition

Beckwith Wiedemann Syndrome is a congenital overgrowth disorder usually present at birth. BWS is characterized by large body size, enlarged organs, macroglossia (enlarged tongue), midline abdominal wall defects (omphalocele/exomphalos, umblicial hernia, diastasis recti), neonatal hypoglycemia and greatly increased risk of childhood cancer, particularly liver and kidney tumors.

 

Beckwith Wiedemann Syndrome

History

In the 1960s, Dr. John Bruce Beckwith, an American pathologist and Dr. Hans-Rudolf Wiedemann, a German pediatrician, independently reported cases of a proposed new syndrome. Originally termed EMG syndrome (for exomphalos, macroglossia, and gigantism), this syndrome over time became known as Beckwith–Wiedemann syndrome or Wiedemann Beckwith syndrome.

Originally, Dr. Hans-Rudolf Wiedemann (born 16 February 1915, Bremen, Germany, died 4 August 2006, Kiel) coined the term exomphalos-macroglossia-gigantism (EMG) syndrome to describe the combination of congenital abdominal wall defects as hernia (exomphalos), large tongues (macroglossia), and large bodies and/or long limbs (gigantism). Over time, this constellation was renamed Beckwith-Wiedemann syndrome following the autoptical observations of Prof. John Bruce Beckwith (born 18 September 1933, Spokane, Washington), who also observed a severe increase in the size of the adrenal glands in some of these patients.

Epidemiology of Beckwith wiedemann syndrome

Beckwith-Wiedemann syndrome affects males and females in equal numbers. The incidence is estimated to occur in 1 in 13,700 individuals in the general population. Because people who are mildly affected may go undiagnosed, it is difficult to determine the true frequency of BWS in the general population.

Risk factors of beckwith wiedemann syndrome

The risk factors for Beckwith-Wiedemann Syndrome include the following:

• Children conceived using in-vitro fertilization, or by other artificial procedures, seem to be at a higher risk of BWS, than a normally conceived child
• Children born in families with a history of BWS may be more vulnerable

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

Causes

Possible causes for Beckwith-Wiedemann syndrome are:

• Methylation defects at chromosome 11p15:Methylation defects could add or delete a mark, which would result in a gene being “turned on” when it should be “turned off,” or “off” when it should be “on.”
• Uniparental disomy (UPD) at chromosome 11p15: UPD occurs when both copies of 11p15 are inherited from only one parent. In cases of UPD in Beckwith-Wiedemann syndrome, both copies of chromosome 11p15 are inherited from the father (paternal UPD). In these cases, the patient expresses only the genes from the father’s chromosome without being counterbalanced by the mother’s.
• Alterations, known as mutations, of the CDKN1C gene, or rarely the regions where methylation marks are made, can occur.
• Chromosomal abnormalities at 11p15: These changes can include deletions (missing genetic material), duplications (extra genetic material), translocations (genes in the wrong place) and inversions (rearranged genetic material).

Chromosomal duplication

While some cases are inherited from a parent, most cases occur as new genetic abnormalities only within the affected child.

Symptoms of beckwith wiedemann syndrome

Signs and symptoms of Beckwith-Wiedemann syndrome include:

• Large size for a new-born
• Red birth mark on forehead or eyelids (Nevus flammeus)
• Creases in ear lobes
• Large tongue (macroglossia)
• Low blood sugar
• Abdominal wall defect (umbilical hernia or omphalocele)
• Enlargement of some organs
• Overgrowth of one side of the body (hemihyperplasia/hemihypertrophy)
• Tumor growth, such as Wilms tumors and hepatoblastomas

Complications of beckwith wiedemann syndrome

These complications can occur:

• Development of tumors
• Feeding problems due to enlarged tongue
• Breathing problems due to enlarged tongue
• Scoliosis due to hemihypertrophy

Diagnosis and tests

A pediatrician or a medical geneticist – a doctor specializing in genetic conditions may diagnose Beckwith-Wiedemann based on a physical examination.

Treatment

Treatment varies from child to child, depending on what characteristics the baby has and how severe they are. Treatments may include:

• In new-borns, treatment for low blood sugar, or hypoglycemia, is important to reduce the risk of central nervous system complications, which can result from insufficient nutrition to the brain.
• New-borns with defects in the abdominal wall will have the defect repaired.
• Infants with an insufficient airway (due to a large tongue) may need a breathing tube.
• Since large tongues can interfere with feeding, some children may need to be fed with special nipples or given tube feedings.
• Children should be screened for tumours, using abdominal ultrasound and serum alpha fetoprotein (AFP), every three months until 8 years of age, and tumours should be treated as needed.
• Children with much enlarged tongues may benefit from surgery to reduce the size of the tongue at 2 to 4 years of age. This procedure can lead to improved feeding and speech.
• Some children benefit from speech therapy.
• Surgery may be performed during puberty to equalize different leg lengths. Surgery may help with facial growth differences as well; the age when these surgeries are performed depends on the child’s specific case.
• Orthodontic treatment is usually needed in adolescence.

Prevention

There is no known prevention for Beckwith-Wiedemann syndrome. Genetic counseling may be of value for families who would like to have more children.