Baller-Gerold syndrome

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.

Many people with Baller-Gerold syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed 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 skin tissue degeneration (atrophy), and small clusters of enlarged 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.

The prevalence of Baller-Gerold syndrome is unknown, but this rare condition probably affects fewer than 1 per million people.

Mutations in the RECQL4 gene cause some cases of Baller-Gerold syndrome. This gene provides instructions for making a protein whose function is not well understood, although researchers believe that it helps stabilize genetic information within the body's cells. This protein probably also plays a role in copying (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.

In a few reported cases, the characteristic features of Baller-Gerold syndrome have been associated with prenatal (before birth) exposure to a drug called sodium valproate. This medication is used to treat epilepsy and certain psychiatric disorders. Several people whose mothers took sodium valproate during pregnancy have been born with an unusual skull shape, distinctive facial features, and abnormalities of the arms and hands.

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.