Form Of Spondyloepimetaphyseal Dysplasia Research Articles

Progressive pseudorheumatoid dysplasia misdiagnosed as juvenile idiopathic arthritis: a case report

BackgroundProgressive pseudorheumatoid dysplasia is a rare, autosomal recessively inherited, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1-inducible signaling pathway protein 3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. Juvenile idiopathic arthritis is the most common chronic rheumatic disease in childhood and has unknown etiology. Clinical features of progressive pseudorheumatoid dysplasia resemble those of juvenile idiopathic arthritis. Patients with progressive pseudorheumatoid dysplasia are usually misdiagnosed as having juvenile idiopathic arthritis.Case presentationA 13-year-old Yemeni female presented to the rheumatology clinic with a history of joint pains, bone pains, and bone deformity for 7 years. Weight and height were below the third percentiles. There was no tender swelling of metacarpophalangeal and interphalangeal joints, and she presented with scoliosis. Radiographs of the hands revealed the widening of the epiphyses. Progressive pseudorheumatoid dysplasia was suspected, and genetic testing for WNT1-inducible signaling pathway protein 1, 2, and 3 was requested with these findings. A homozygous, likely pathogenic variant was identified in the WNT1-inducible signaling pathway protein 3 gene, which confirmed our diagnosis.ConclusionProgressive pseudorheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. It is crucial to consider progressive pseudorheumatoid dysplasia, especially in patients with standard inflammatory markers who are being followed up for juvenile idiopathic arthritis and not improving with antirheumatic intervention.

A new form of severe spondyloepimetaphyseal dysplasia: Clinical and radiological characterization

We report on two patients with a severe form of spondyloepimetaphyseal dysplasia (SEMD). Both patients show normal birth length, early postnatal growth deficiency, severe short stature, flexion contractures in the hips, bowing of the legs with genu varum. Skeletal radiographies show platyspondyly and characteristic vertebral body shape with central indentation of endplates, progressive, and severe metaphyseal changes, very small and irregular proximal femoral epiphyses with severe coxa vara, absence of calcifications, and mild metaphyseal irregularities in upper limbs. The similarities in the skeletal radiographs with SEMD type Strudwick and SEMD matrilin 3 type prompted us to analyze the COL2A1 and MATN3 genes. Direct sequencing of genomic DNA failed to identify any mutation in COL2A1 for both patients and MATN3 sequencing for Patient 1 identified only one heterozygous variant with no predicted damaging effect inherited from an unaffected parent. We therefore conclude that this form of SEMD probably differs from SEMD matrilin 3 type and does not belong to the spectrum of type II collagenopathies. The similarities between our two patients allowed us to propose that they might show a new form of SEMD.

Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation

Spondyloepimetaphyseal dysplasias (SEMD) represent a heterogeneous group of conditions composed of at least 15 well-defined entities. The classification is based on clinical, radiological and molecular findings. Among them, several conditions also include a mental retardation (MR) syndrome, namely Wolcott-Rallison syndrome, Dyggve-Melchior-Clausen syndrome (DMC) and lysosomal storage disorders. Here, we report on a novel form of SEMD with MR in two Pakistani sisters born to first-cousin parents. SEMD, MR, microcephaly, ataxia, facial dysmorphism and hirsutism of back and legs were noted in the two children. Skeletal findings included flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, small carpal bones and narrow iliac wings without lacy pelvis iliac crest. Similarities with DMC prompted us to test and eventually exclude the DMC gene, dymeclin, by direct sequencing. Similarly, we excluded the PAPSS2 gene (3'-alpha phosphoadenosine 5'-phosphosulphate synthase 2) responsible for SEMD Pakistani type. The combination of features observed in the two sisters does not fit with any previously reported SEMD and represents therefore a novel form of autosomal recessive SEMD with MR.

Distinctive new form of spondyloepimetaphyseal dysplasia with severe metaphyseal changes similar to Jansen metaphyseal chondrodysplasia

We report a boy with a unique, "new" form of spondyloepimetaphyseal dysplasia. The conspicuous features of the spinal changes were the delay in ossification of the cervical spine and posterior elements of the thoraco-lumbar spine. The vertebral bodies were of abnormal shape but of normal size and well ossified. The hallmark of epiphyseal changes was markedly delayed ossification (bone age). The severely disturbed metaphyseal ossification was similar to Jansen metaphyseal dysplasia. This pattern of changes has not yet been described in spondyloepimetaphyseal dysplasia.

Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

We describe a large inbred kindred from a remote area of Pakistan, comprising eight generations, with a distinct form of spondyloepimetaphyseal dysplasia (SEMD). We evaluated 16 affected individuals: 11 males and 5 females. Analysis of the pedigree strongly suggests autosomal recessive inheritance, and consanguineous loops could account for all the affected individuals being homozygous for the abnormal allele. The clinical findings included short stature evident at birth, short bowed lower limbs, mild brachydactyly, kyphoscoliosis, an abnormal gait, enlarged knee joints, precocious osteoarthropathy, and normal intelligence. Radiographs demonstrated delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse, early osteoarthritic changes, primarily in the spine and hands, and mild brachydactyly. Mild metaphyseal abnormalities were seen predominantly at hips and knees. This distinctive phenotype is distinct from other autosomal recessive forms of SEMD because of the mild degree of metaphyseal involvement, the type of brachydactyly, and the absence of loose joints or other clinical findings.

Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

Linkage studies of a Missouri kindred with autosomal dominant spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity.

A four-generation kindred (14 affected and 10 unaffected members) from Missouri, U.S.A. in which spondyloepimetaphyseal dysplasia (SEMD) had been inherited as an autosomal dominant disorder was investigated for linkage to 13 candidate loci: COL2AI, COL9AI, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, PSACH, FGFR3, decorin, CRTL1, COMP, and PTHRP. Mutations of COL2A1, COL9A2, COL10, and FGFR3 have been reported previously in the Strudwick type of SEMD, multiple epiphyseal dysplasia type 2 (EDM2), the Schmid type of metaphyseal dysplasia, and in achondroplasia, respectively, and the pseudoachondroplasia (PSACH) locus has been mapped to chromosome 19p12. In addition, mutations in COL9 and COL11A are associated with murine forms of degenerative joint disease and chondroplasia, respectively. The family proved informative for 12 of the 13 loci and was uninformative at the decorin locus. Linkage between this form of SEMD, designated the Missouri variant, SEMDMO, and the 12 informative candidate loci was excluded (LOD scores < -2.00 at theta = 0.005 to 0.15), thereby indicating further genetic heterogeneity in these inherited disorders of bone and cartilage development.

Spondyloepimetaphyseal dysplasia and abnormal dentition in siblings

The clinical and radiological features are described in male and female siblings with a unique form of spondyloepimetaphyseal dysplasia. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, these children also have thin tapering fingers with accentuated palmar creases and abnormal dentition with oligodontia and pointed incisors. Parental consanguinity suggests that this is an autosomal recessive disorder.

New X linked spondyloepimetaphyseal dysplasia: report on eight affected males in the same family.

We report on a probably new form of spondyloepimetaphyseal dysplasia (SEMD) with an X linked inheritance pattern. Eight males were affected in the same family. We were able to examine three adult patients and we studied the skeletal radiological aspect of one of these patients at 2 years 6 months and at 9 years of age. The main clinical features are severe short trunked dwarfism, brachydactyly, normal facies, and normal intelligence. Radiologically, the diaphyses of all the long bones are short and broad. The epiphyses of the distal portion of the femora and those of the proximal and distal portions of the tibia are embedded in their metaphyses and there is marked narrowing of the intercondylar groove. There is moderate platyspondyly. Several vertebrae show an anterior tongue in infancy and severe irregularities of the upper and lower surfaces are present in adulthood. The 11th or 12th thoracic vertebra is wedge shaped. The pelvis is narrow. The distal ulnae and fibulae are disproportionately long. The hands show radial deviation and brachydactyly is present in the hands and feet. This X linked SEMD was not detectable at birth.