Baller-Gerold Syndrome

Excerpt

Clinical characteristics: Baller-Gerold syndrome (BGS) can be suspected at birth in an infant with craniosynostosis and upper limb abnormality. The coronal suture is most commonly affected; the metopic, lambdoid, and sagittal sutures may also be involved alone or in combination. Upper limb abnormality can include a combination of thumb hypo- or aplasia and radial hypo- or aplasia and may be asymmetric. Malformation or absence of carpal or metacarpal bones has also been described. Skin lesions may appear anytime within the first few years after birth, typically beginning with erythema of the face and extremities and evolving into poikiloderma. Slow growth is apparent in infancy with eventual height and length typically at 4 SD below the mean.

Diagnosis/testing: The diagnosis of BGS is established in a proband with typical clinical findings and/or the identification of biallelic pathogenic variants in RECQL4 by molecular genetic testing.

Management: Treatment of manifestations: Surgery before age six months to repair bilateral craniosynostosis; pollicization of the index finger as needed to create a functional grasp; sunscreen use with poikiloderma to protect against skin cancer.

Surveillance: Because individuals with allelic RECQL4 disorders are at increased risk for osteosarcoma and lymphoma, attention to clinical findings (e.g., bone pain, swelling, and/or limp) for osteosarcoma and lymph node enlargement or generalized symptoms (e.g., fever or unexplained weight loss) for lymphoma is recommended for those with BGS.

Agents/circumstances to avoid: Sun exposure because of risk for skin cancer.

Genetic counseling: Baller-Gerold syndrome is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and therefore carry one pathogenic variant. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible if both pathogenic variants in the family have been identified.