PAPSS2‐related brachyolmia: Clinical and radiological phenotype in 18 new cases

Abstract

Brachyolmia is a skeletal dysplasia characterized by short spine-short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from

Novel Inactivating Homozygous PAPSS2 Mutation in Two Siblings With Disproportionate Short Stature

“…In addition to the brachyolmia, the fact that the affected siblings showed decreased DHEA-S supports the impaired sulfonation of DHEA as a result of the identified variant. Previous reports in the literature indicate that the skeletal manifestations in PAPSS2 defects vary clinically and radiologically, even with the same gene variant [1].…”

“…Congenital causes of disproportionate short stature (DSS) include the heterogeneous spectrum of skeletal dysplasias. Brachyolmia is characterized by short trunk, platyspondyly (flattened vertebral bodies) and mild long bone abnormalities [1]. Three types of brachyolmia are related to variants in PAPSS2, gene coding for PAPSS2 (3'-PhosphoAdenosine 5'-Phosphosulphate Synthetase 2) [1].…”

“…Brachyolmia is characterized by a short trunk, platyspondyly (flattened vertebral bodies), and mild long-bone abnormalities. 1 Three types of brachyolmia are related to variants in the PAPSS2 gene, coding for PAPSS2 (3′-phosphoadenosine 5′-phosphosulfate synthetase 2). 1 This enzyme converts inorganic sulfate and adenosine triphosphate into 3′-phosphoadenosine sulfate, which serves as a sulfate donor for the sulfonation of dehydroepiandrosterone (DHEA) to dehydroepiandrosterone sulfate (DHEA-S) by sulfotransferase A1 (SULT2A1, Supplementary Fig.…”

Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis

“…Compound heterozygous mutations in PAPSS2 cause hyperandrogenism, premature pubarche, and hyperandrogenic anovulation, in addition to a short stature and skeletal dysplasia, which may result from a low level of serum dehydroepiandrosterone sulfate with increasing androgen (Table 5; Noordam et al, 2009). Furthermore, brachyolmia, which is characterized by a short stature, short trunk, irregular endplates, narrow intervertebral disks, precocious calcification of rib cartilages, a short femoral neck, mildly shortened metacarpals, and a normal intelligence and facies, are also caused by compound heterozygous and homozygous mutations in PAPSS2 (Table 5; Miyake et al, 2012;Iida et al, 2013;Bownass et al, 2019). PAPSS2 mutation might present a gradation of the phenotypic spectrum from brachyolmia to spondylo-epiphyseal and spondylo-epimetaphyseal dysplasia of the Pakistani type (Miyake et al, 2012).…”

A Rare Case of Brachyolmia with Amelogenesis Imperfecta Caused by a New Pathogenic Splicing Variant in LTBP3

“…Currently, four major forms of brachyolmia have been recognized, including the Hobaek (OMIM 271530) and Toledo (OMIM 271630), Maroteaux (OMIM 613678), dominant (OMIM 113500), and brachyolmia with mild epiphyseal and methaphyseal changes (OMIM 612847) types. The first two forms together with type 4 are characterized by autosomal recessive inheritance associated with biallelic variations in the PAPSS2 gene (10q23.2q23.31) [ 2 ]. Both Hobaek and Toledo forms are characterized by scoliosis, platyspondyly with elongated vertebral bodies, overfaced pedicles and irregular, narrow invertebral spaces, with the latter showing corneal opacities and precocious calcification of the costal cartilagine.…”