Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy).

Autor: Alessandri JL; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France. Electronic address: jean-luc.alessandri@chu-reunion.fr., Celse T; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Spodenkiewicz M; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Calaya A; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Dumont C; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Jacquemont ML; Service de Génétique Médicale, Département de Pédiatrie, CHU Sainte-Justine, Québec, Canada., Bertaut-Nativel B; Registre des Malformations Congénitales de La Réunion, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Boumahni B; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Rémy M; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Ferroul F; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Guilly S; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Huby T; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Irabé M; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Laurens T; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Munier P; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Morel G; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Payet F; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Randrianaivo H; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France; Registre des Malformations Congénitales de La Réunion, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Doray B; Service de Génétique Médicale, Centre Hospitalier Universitaire de La Réunion, La Réunion, France., Dospeux J; Centre Pluridisciplinaire de Diagnostic Prénatal, Centre Hospitalier Universitaire de La Réunion, La Réunion, France.
Jazyk: angličtina
Zdroj: European journal of medical genetics [Eur J Med Genet] 2024 Jun; Vol. 69, pp. 104940. Date of Electronic Publication: 2024 May 03.
DOI: 10.1016/j.ejmg.2024.104940
Abstrakt: Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in B4GALT7 gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region. B4GALT7 encodes galactosyltransferase I, one of the enzymes involved in the biosynthesis of the linker region. Conditions caused by pathogenic biallelic variants in genes implicated in the synthesis of the tetrasaccharide linker of PG are known as linkeropathies. Prenatal features are rarely described in this group of chondrodysplasias. We present a series of 12 unpublished patients having LRS and describe the perinatal phenotype. All the patients had a prenatal growth restriction with brevity of limbs. The other features revealed by ultrasounds were increased nuchal translucency at 10-12 weeks of gestation (50 %), feet abnormalities (clubfeet or metatarsus varus) (25 %), dislocation affecting at least one large joint (elbow, knee, wrist) (25 %). Bilateral bowing of femora was noted for two fetuses. Fibular hypertrophy was noted for one fetus. Prenatal helical computed tomography (CT) performed in three pregnancies showed additional data such as bowing of the forearm bones, proximal radio-ulnar synostosis, or dislocation of large joints. Prenatal sonographic and helical CT findings led to the prenatal diagnosis of LRS in four patients. We confirm that the neonatal clinical picture of LRS has an important overlap with that reported in patients with B4GALT7 deficiency outside La Réunion Island and other linkeropathies. The core of the phenotypic spectrum combines low birth height, micromelia, hypermobility, dislocation of at least one large joint, facial features with prominent eyes, microstomia, depressed nasal bridge, and midface hypoplasia. Other clinical features include clubfeet (33%), bifid thumb in one patient, and cardiac abnormalities in two patients. Radiological findings include radio-ulnar synostosis (75%), metaphyseal flaring, precocious carpal ossification, and a Swedish key appearance of the proximal femora. Finally, we also report radiological features rarely described in B4GALT7-linkeropathies, including bowing of the femora and fibular hypertrophy. Our results confirm the phenotypic continuum of LRS within linkeropathies with some additional findings, including a high frequency of clubfeet usually described in B3GALT6-linkeropathies, the presence of congenital heart diseases usually described in B3GAT3-linkeropathies, and a high frequency of metaphyseal flaring usually reported in B3GALT6 or XITLT1-linkeropathies. This is the first study that describes the perinatal phenotype in a cohort of patients with LRS. This study can help improve the prenatal diagnosis of the linkeropathies and add this group of conditions to the differential diagnosis of chondrodysplasias with multiple dislocations. In view of the founder effect for LRS in La Réunion Island, this disease should be suspected in fetuses with growth restriction and micromelia. Thus in case of LOH which include B4GALT7 identified in SNP-array, we recommend performing a targeted Sanger sequencing for the recurrent mutation c.808C > T; p. (Arg270Cys).
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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