Summary

Baller-Gerold syndrome is characterized by the association of coronal craniosynostosis with radial ray anomalies (oligodactyly, aplasia or hypoplasia of the thumb, aplasia or hypoplasia of the radius). Around 30 cases have been reported but the prevalence of the syndrome is unknown. Craniosynostosis and radial ray anomalies present at birth and are associated with facial dysmorphism (brachycephaly, ocular exophthalmia, frontal bossing, nasal hypoplasia, small mouth, ogival palate). An inconstant poikiloderma can appear during the first months of life. Delayed growth is nearly always present, usually around -4SD. Patellar aplasia or hypoplasia can be observed during childhood. Intelligence is usually normal. Patients have a predisposition to cancer, in particular osteosarcoma. Baller-Gerold syndrome is inherited in an autosomal recessive manner and is secondary to mutations of the RECQL4 gene (8q24.3). RECQL4 is a member of the RecQ helicase gene family which cause other diseases predisposing to cancer. The proportion of patients with mutations in this gene has not been determined. Diagnosis of Baller-Gerold syndrome relies on clinical criteria. Given the numerous differential diagnoses, finding a mutation of the RECQL4 gene can help clarify the diagnosis spectrum, genetic counseling and management. The principal differential diagnoses include Rothmund-Thomson syndrome (RTS) and RAPADILINO syndrome, also secondary to mutations of the RECQL4 gene (see these terms). A phenotypic continuum between these diseases has been suggested by numerous authors: it is possible that they represent different expressions of the same pathology. Other differential diagnoses include Roberts syndrome and Fanconi anemia, which are frequently associated with radial ray anomalies but rarely with craniosynostosis, and Saethre-Chotzen syndrome which is characterized by coronal craniosynostosis usually without radial ray anomalies (see these terms). The combinationof craniosynostosis and radial ray hypoplasia is also associated with fetal valproic syndrome (see this term). The presence of poikiloderma allows other pathologies to be excluded. Prenatal diagnosis by chorionic villus sampling (CVS) is suggested when pathogenic mutations of the RECQL4 gene are found in an index case (homozygous or heterozygous). Ultrasound can be used to identify limb anomalies and an abnormally shaped cranium. Treatment consists of surgery of the bilateral craniosynostosis in the first 6 months of life and, if necessary, pollicization of the index finger for thumb reconstruction. When monitoring patients particular clinical attention should be paid to bone pain, limpness or fractures, because of the risk of osteosarcoma. Exposure to the sun should be avoided because of a risk of skin cancer and photosensitivity. The prognosis for patients with mutations of the RECQL4 gene, homozygous or heterozygous, is related to an increased risk of cancer.

Expert reviewer(s)

• Pr Laurence FAIVRE-OLIVIER