Diaphanospondylodysostosis (DSD): Confirmation of a recessive disorder with abnormal vertebral ossification and nephroblastomatosis

Abstract

We report on four patients from three families, with similar radiological findings: absent (or severely delayed) ossification of vertebral bodies and associated anomalies. The babies were stillborn or died soon after birth of respiratory insufficiency. Two patients are sibs (female and male) born to first cousin Malian parents. The two others were non-consanguineous. This perinatally lethal entity comprises short neck, short wide thorax, and normally shaped limbs. Associated, inconstant anomalies are myelomeningocele, cystic kidneys with nephrogenic rests (in the sibs), and cleft palate. Radiologically, the hallmarks are absence of ossification of the vertebral bodies and sacrum, abnormal position of the vertebral pedicles, which are lamellar and angulated, ribbon-like ribs reduced in number, narrow pelvis, upward widening of the iliac wings, and unusual tilt of the ischiopubic rami, contrasting with the normal appendicular skeleton. Maroteaux briefly described one of the patients in the 2002 edition of "Maladies osseuses de l'enfant" and three sibs with similar renal and radiological findings were reported in 2003 in this Journal. Combined with the latter cases, these four new patients allow delineation of a specific lethal AR syndrome with ossification defect of the axial skeleton and renal dysplasia. We propose to name this entity diaphanospondylodysostosis.

Long‐term survival with diaphanospondylodysostosis (DSD): Survival to 5 years and further phenotypic characteristics

“…Gonzales et al [2005] reported four patients from three different families that mimicked the radiologic, clinical, and renal findings reported by Prefumo et al All were stillborn or died soon after birth of respiratory insufficiency. Two patients were siblings of a consanguineous union lending support to an autosomal recessive pattern of inheritance.…”

A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD)

“…We describe two families in which children or fetuses were affected with a severe skeletal malformation syndrome, compatible with the rare diagnosis of “Newly recognized autosomal recessive syndrome with abnormal vertebral ossification, rib abnormalities, and nephrogenic rests,” described by Prefumo et al [2003], and later designated as DSD by Gonzales et al [2005]. One of the cases we describe is unusual for survival to 15 months, compared to in utero or perinatal death observed in most cases.…”

Prenatal diagnosis of diaphanospondylodysostosis (DSD): a case report

“…Gonzales et al. reported four patients from three families with similar findings of the skeletal system and nephroblastomatosis in 2005. The babies were stillborn or died shortly after birth of respiratory insufficiency.…”

“…DSD is caused by homozygous or compound heterozygous mutations in the bone morphogenetic protein‐binding endothelial regulator protein (BMPER) gene on chromosome 7p14. There are only case reports in genetic and pediatric literature published since 2003 and few reports on prenatal diagnosis so far . We present a first case with prenatal diagnosis of DSD in which molecular genetic analysis was performed, and a mutation was found which to our knowledge had not been published in the literature yet.…”