Nationwide survey of Baller-Gerold syndrome in Japanese population

Abstract

Baller-Gerold syndrome (BGS) is a rare autosomal genetic disorder characterized by radial aplasia/hypoplasia and craniosynostosis. The causative gene for BGS encodes RECQL4, which belongs to the RecQ helicase family. To understand BGS patients in Japan, a nationwide survey was conducted, which identified 2 families and 3 patients affected by the syndrome. All the three patients showed radial defects and craniosynostosis. In one patient who showed a dislocated joint of the hip and flexion contracture of both the elbow joints and wrists at birth, a homozygous large deletion in the RECQL4 gene was identified. This is the first reported case of BGS in Japan caused by RECQL4 gene mutation.

Phenotypic Overlap of Roberts and Baller-Gerold Syndromes in Two Patients With Craniosynostosis, Limb Reductions, and ESCO2 Mutations

“…Table 1 summarizes the distinctive clinical features of BGS and RBS individuals whose clinical phenotype could be confirmed by molecular analysis of the respective RECQL4 and ESCO2 genes. Craniosynostosis is a distinctive sign of BGS as it has been reported in 82% (9/11) of BGS patients with RECQL4 alterations (4, 10–12, 32, 33) but in RBS with ESCO2 pathogenic variants only in the 2 patients herein described and in 2 patients of the literature, for whom no details or images are provided (29). Conversely, hemangioma on the face, recorded in 30 ESCO2 + patients (29, 34, 35) and in only one RECQL4 + patient (10, 32), as well as intellectual disability, assessed in 23 ESCO2 + patients (29, 34) and in 1 RECQL4 + patient (4), are prominent in RBS.…”

“…Moreover, 90% (10/11) BGS (10–12, 32, 33, 36) and all RBS (14, 27–29, 34, 35, 37, 38) patients present with radial alterations (hypo/aplasia) and most of them manifest additional upper and lower limb malformations. Pre-axial upper limb defects are similar in BGS and RBS: ulnae hypoplasia, club hands, thumbs aplasia/hypoplasia, clinodactyly, and oligodactyly, though humeral reduction can be also present in RBS.…”

“…About 70 clinically diagnosed BGS patients are reported in the literature but, subsequently to further in-depth analysis, a different diagnosis has been formulated for almost 20 of them (3, 5–9). To date, biallelic alterations in RECQL4 gene (OMIM * 603780), encoding a protein of the RECQ helicase family with multiple functions in the maintenance of genome integrity, have been found in a subgroup of 11 BGS patients from 7 families (1, 4, 10–12). To note, 4 out of 5 BGS patients, who could be evaluated, present with poikiloderma, a chronic cutaneous alteration manifesting in the first years of life in most of the RECQL4 -mutated patients (4, 10, 11).…”

DNA Repair Syndromes and Cancer: Insights Into Genetics and Phenotype Patterns

“…Second, Baller-Gerold syndrome (BGS), first reported by Cohen in 1975, was based on three patients described in 1950 by Baller and 1959 by Gerold in German literature (186). Fewer than 40 patients have been described with an unknown prevalence (187). BGS patients with RECQL4 mutations have craniosynostosis, upper-limb anomalies, short stature, and poikiloderma (188).…”

Baller-Gerold Syndrome in a Premature Infant with a Mutation in the RECQL4 Gene

“…Baller-Gerold syndrome (BGS) is a rare genetic disorder, also referred to as craniosynostosis-radial aplasia syndrome, which was first described independently by Baller 1) in 1950 and Gerold 2) in 1959. It is characterized by craniosynostosis, particularly of the coronal sutures, a dysmorphic face, such as a prominent forehead, ocular proptosis, hypertelorism, and a small mouth, and limb abnormalities, especially in the upper extremities, including missing fingers and malformed or absent thumbs 3,4) . In addition to phenotypic variability, addi tional features presented in BGS include failure to thrive, developmental delay, and systemic anomalies such as congenital heart disease (ventricular septal defect and patent ductus arteriosus), renal agenesis, an imperforate anus, and nervous system abnormalities (agenesis of the corpus callosum, or seizure disorders) 5)…”