Baller-Gerold Syndrome - An Insight

Introduction

Baller-Gerold syndrome, also called BGS or craniosynostosis with radial defects, is a rare genetic abnormality that shows symptoms which affect the form and function of the individuals, especially their skeletal structure. It is inherited in individuals whose parents carry a copy of the gene, who may not show the signs and symptoms of the condition.

What Is Baller-Gerold Syndrome?

It is a rare genetic condition that is characterized by the fusion of skull bones and abnormal formation of arms and hands. It is mainly caused due to the mutation of a gene RecQL4. This gene provides instructions for making a protein called RecQ helicases. These proteins are enzymes that bind to the genetic material and unwind them. The DNA (deoxyribonucleic acid), which is the genetic material, is temporarily unbound due to the necessity for replicating and repairing the DNA. This protein helps stabilize genetic information and is important in replicating and repairing DNA.

Mutations of the gene RecQL4 stop the cells from producing any protein and hamper the function. Limited protein functionality can prevent the normal DNA repair and replication process, leading to damage to the person's genetic information in the long run.

It is also associated with exposure to sodium valproate drug, which is used to treat psychiatric disorders and epilepsy (continous seizures).

What Are the Symptoms of Baller-Gerold Syndrome?

Symptoms of the Baller Garold syndrome can begin at the time of birth. It is essential to note the first symptoms in an individual as it helps the medical provider to provide a better diagnosis.

Craniofacial Findings:

• Brachycephaly (increase in the ratio of skull length and width).

• Prominent forehead.

• Proptosis (protrusion of eyeball).

• Large fontanelles.

• Short nose.

• High-arched palate.

• Narrow mouth.

Skeletal Deformities:

• Upper Limb Defect: Hyperplasia (increase in the growth of cells) of the thumb and radius. Malformation of carpel and metacarpels.

• Knee Abnormality: Delay in the ossification of the knee cap or absence of the same.

Skin Findings:

• Erythema (redness) in the face and extremities (arms or legs).

• Poikiloderma (reddish brown patches near the neck).

How is Baller-Gerold Syndrome Diagnosed?

Clinical findings can give a professional diagnosis, and hence proper clinical examination should be done prior.

• Coronal Craniosynostosis: The abnormal shape of the skull with protrusion of the eyeball and a prominent head which an X-ray or CT (computed tomography) reconstruction can confirm, can lead to a proper diagnosis.

• Radial Ray Defect: Hypoplasia or aplasia of the thumb or the arm's bone called radius can also determine the presence of the syndrome.

• Poikiloderma: Increased (reddish) or decreased pigmentation of the skin with talengectesias (increase in the width of the blood vessels) can be seen.

After acquiring the provisional diagnosis by clinical findings, molecular genetic testing is done for the confirmation of the diagnosis.

• The Molecular Genetic Testing: The approach includes gene-targeted testing and comprehensive genomic testing. Gene-targeted testing needs the clinician to determine the involved gene. On the other hand, genomic testing does not require it. As the clinical appearance of the symptoms related to this syndrome is broad, the condition can be diagnosed with gene-targeted testing in individuals with distinctive findings, whereas in clinical conditions where the characteristics cannot be distinguished from other syndromes with defective bone growth are to be diagnosed using comprehensive genomic testing.

• Ultrasound Examination: Limb shortening can be identified by ultrasound examination along with radial hypoplasia and abnormal head shape. Examination through ultrasound can reveal the findings from a gestation period of 14 weeks onwards in pregnant women at risk. Prenatal testing perspectives can differ among medical professionals as well as within families. It is a personal decision and can be helpful.

What Is the Treatment Protocol for Baller-Gerold Syndrome?

Management of the syndrome Baller-Gerold syndrome begins with certain evaluations following the diagnosis.

• A clinical geneticist or genetic counselor consultation.

• Craniofacial specialist on neurosurgeon consultation for the evaluation of bones in the cranium.

• Orthopedic surgeon assessment evaluates the function of the hand in the arm and the need for surgery.

• Evaluation by dermatologist for the treatment of poikiloderma.

Treatment Manifestations:

• Craniosynostosis is managed by specialists in the cranium and neurosurgeons. Bilateral craniostosis can be treated with surgery performed before the age of six months.

• Index finger pollicization surgery is done to restore the grasp of the hand. This procedure was beneficial and had satisfactory results in individuals without thumb. Many individuals are still+ able to manage their life without orthopedic intervention.

• The presence of poikiloderma may insist on the use of sunscreen to protect against the risk of skin cancer due to exposure to ultraviolet radiation.

• Oncology should be sorted in case of cancer. Excessive exposure to the sun has to be avoided as there is an increased risk of skin cancer.

What Is Genetic Counseling?

Genetic counseling is a process of educating individuals and families on modes of inheritance and the results of genetic disorders, which can help them make personal and medical decisions. Family history and genetic testing are used to obtain a clear genetic status of family members.

Mode of Inheritance:

The BGS syndrome is an autosomal inherited recessive disorder.

Risk of BGS Syndrome to Family Members:

• Parents of a Proband: If affected child's parents are the carrier of one variant which is pathogenic, they are heterozygotes that do not show symptoms and are at low risk of developing a disorder.

• Siblings of a Proband: Siblings of affected individuals have a one-fourth chance of being affected and the major chance of being a symptomatic carrier.

• Offspring of a Proband: The offspring of an individual with the syndrome are carriers for an infected variant.

• Detection of a Carrier: Identification of the pathologic variance of the ReCQL4 gene in the family is required for testing a carrier in relatives at risk.

Conclusion

The genetic syndrome BGS is an area of normality that affect the growth of bones (especially the bones of the skull and limbs). Fusion of skull bones and limited development of bones in the arms are the prominent symptoms. They can also show skin condition that resembles discolored patches or breakdown of skin. The symptoms of this disorder can coincide with the symptoms of Roathmund-Thomson syndrome, and hence diagnosis is an important part that determines the treatment.