Baller-Gerold Syndrome (BGS) is a rare genetic disorder with congenial onset, inherited as an autosomal recessive trait and characterized by the malformations in the growth plates of the bones of the hands and arms as well as abnormal fusion in skull bones. The prevalence of BGS is unknown, but is thought to be less than 1 in 1,000,000. Patients affected have parents whom are both carriers of the gene, and have been found to be in closely related.
Baller-Georld Syndrom is caused by a mutation in RECQL4 gene on the long end of chromosome 8. More specifically, the cytogenetic location is 8q24.3 and the molecular location is from the base pair 145,736,666 to 145,743,209.
Characteristics of the Disease
Infants head my appear abnormally short or wide due to the premature fusion of the skull bones. The prematurely fused skull bones of patients with Baller-Gerold Syndrome occurs along the growth lines on the head that extend ear to ear, the coronal structures, this can also lead to the absence of a fontanelle, soft spot on in skull of a new born. Other than the head forming short or wide, the profile can be affected, resulting in a prominent forehead, bulging eyes with shallow eye sockets which can lead to widely spaced eyes, also the face is characterized by a small mouth and a saddle-shaped or underdeveloped nose.
Radial Ray Malformations
Patients with Baller-Gerold Syndrome have been documented to have aplasia (absence) or hypoplasia (underdevelopment) of the radius where the ulna is formed unusually short and curved. Furthermore patients with BGS can have bone abnormalities of the hands which can include missing fingers, malformed or underdevelopment or absent thumbs, and in some cases an extra digit.
Symptoms vary in each patient, but the occurrence of rashes a few months after birth has been documented. These rashes appear on the arms and legs as patchy discolorations that can be areas of skin degeneration and can spread with time.
Treatment or Management of the Condition
Treatment is available in the form of surgery which seeks relieve pressure on the brain, allowing for proper brain growth within the skull, and to improve the quality of life of the child through the enhancement of the child's head.
To treat the absence or underdevelopment of the arm and hand bones, surgery is preformed to repair the radius and create functionality of hands to improve the ability of grasping and various motions of the hand and arm.
The mutations responsible for causing Baller-Gerold Syndrom reside in the RECQL4 gene. The function of the protein is not to known as there are so few cases of BGS. It its hypothesized that the protein plays a role in stabilization of the cell genetic material, DNA, and that with a deletions or replacements of the protein will lead to improper replication or repair of DNA. These can result in a sever damaging of a person's genetic code.
To test for the present of the mutation of the RECQL4 gene sequence analysis can be preformed on the entire gene to include exon and introns. Because of it's rarity, of the families that have had this testing preformed there has been a rate of 100% accuracy.
Also deletion/duplication analysis is clinically available, but there have been no significant results to explain its purpose in testing of this mutation because there have been no deletions or duplications of RECQL4 that result in BGS.
Other relevant information
With the variation of symptoms for Baller-Gerold Syndrome it can have overlap with other similar disorders like Rothmund-Thomson syndrome and RAPADILINO (radial ray defect; patellae hypoplasia or aplasia and cleft or highly arched palate; diarrhea and dislocated joints; little size and limb malformation; nose slender and normal intelligence) syndrome. Both of these syndromes are also characterized by slow growth in the bones, radial ray defects, abnormalities of the arms, hands or skull. The mutation in RECQL4 gene can cause all of these conditions.
Due to the nature of the disease and the characterization of skin rash and discoloration, there is a caution to those affect to avoid sun exposure because of a higher risk of obtaining skin cancer.
It has been documented in patients with BGS and similarly of those affected with RAPADILINO and Rothmund-Thomson syndrome, there has been cases of lymphoma. Thus it is necessary to watch for lymph node swelling.
In some case of Baller-Gerold Syndrome, mothers during pregnancy had exposure to a drug, sodium valproate, used in treatment of epilepsy and psychiatric disorders.The patients born to these mothers have characteristics that match the one that characterize BGS.
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