Baller-Gerold syndrome

Other Names: BGS; Craniosynostosis-radial aplasia syndrome; Craniosynostosis with radial defects

Baller-Gerold syndrome is a rare condition characterized by the premature fusion of certain skull bones (craniosynostosis) and abnormalities of bones in the arms and hands.

Epidemiology

The prevalence of Baller-Gerold syndrome is unknown, but this rare condition probably affects fewer than 1 per million people. Fewer than 40 cases have been reported in the medical literature.

Cause

Mutations in the RECQL4 gene cause some cases of Baller-Gerold syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to [[DNA[[ and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.

Mutations in the RECQL4 gene prevent cells from producing any RECQL4 protein or change the way the protein is pieced together, which disrupts its usual function. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how a loss of this protein's activity leads to the signs and symptoms of Baller-Gerold syndrome.

This condition has been associated with prenatal (before birth) exposure to a drug called sodium valproate. This medication is used to treat epilepsy and certain psychiatric disorders. Some infants whose mothers took sodium valproate during pregnancy were born with the characteristic features of Baller-Gerold syndrome, such as an unusual skull shape, distinctive facial features, and abnormalities of the arms and hands. However, it is unclear if exposure to the medication caused the condition.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

People with Baller-Gerold syndrome have prematurely fused skull bones, most often along the coronal suture, the growth line that goes over the head from ear to ear. Other sutures of the skull may be fused as well. These changes result in an abnormally shaped head, a prominent forehead, and bulging eyes with shallow eye sockets (ocular proptosis). Other distinctive facial features can include widely spaced eyes (hypertelorism), a small mouth, and a saddle-shaped or underdeveloped nose.

Bone abnormalities in the hands include missing fingers (oligodactyly) and malformed or absent thumbs. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are called radial ray malformations.

People with Baller-Gerold syndrome may have a variety of additional signs and symptoms including slow growth beginning in infancy, small stature, and malformed or missing kneecaps (patellae). A skin rash often appears on the arms and legs a few months after birth. This rash spreads over time, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These chronic skin problems are collectively known as poikiloderma.

The varied signs and symptoms of Baller-Gerold syndrome overlap with features of other disorders, namely Rothmund-Thomson syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.

Diagnosis

Baller-Gerold syndrome is diagnosed based on a clinical examination, the symptoms, and confirmed by genetic testing. BGS can be diagnosed during pregnancy using an ultrasound examination and prenatal testing.

Baller-Gerold syndrome should be suspected in individuals with a combination of the following findings:

• Coronal craniosynostosis, manifest clinically as abnormal shape of the skull (brachycephaly) with ocular proptosis and prominent forehead and confirmed by skull x-ray or (preferably) 3D-CT reconstruction
• When the coronal sutures are fused, the orbit is pulled forward. The coronal sutures cannot be discerned on the frontal view, and the same holds true for the lambdoidal sutures.
• Radial ray defect, manifest as aplasia or hypoplasia of the thumb, and/or aplasia or hypoplasia of the radius

Note: Radiographs may be necessary for confirmation of minor radial ray malformations.

• Growth restriction
• Poikiloderma consisting of hyper- and hypopigmentation of the skin with punctate atrophy and telangiectases

The diagnosis of Baller-Gerold syndrome is established in a proband with typical clinical findings and/or by identification of biallelic pathogenic variants in RECQL4 on molecular genetic testing.

Treatment

Treatment for Baller-Gerold syndrome is based on managing the symptoms. This may include surgery to fix the bones of the skull and other skeletal abnormalities. In addition, some may need surgery to reconstruct the hand.

Craniosynostosis should be managed by neurosurgical/craniofacial specialists. When craniosynostosis is bilateral, surgery is usually performed before age six months.

Pollicization of the index finger to restore a functional grasp has had satisfactory results in a number of persons with absence of the thumb . However, many children with aplasia of the thumb are able to function without orthopedic surgical intervention.

If poikiloderma is present, sensible use of sunscreens may protect against potential risk for skin cancer due to UV exposure.

If cancer arises, medical care should be sought from an oncologist familiar with the type of cancer.

NIH genetic and rare disease info

• NIH info on Baller-Gerold syndrome

Baller-Gerold syndrome is a rare disease.

Baller-Gerold syndrome Resources
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