Spondylometaphyseal dysplasia is an extremely rare genetic disorder of the bones, primarily involving the axial skeleton, with short stature, abnormally shaped vertebrae, and scoliosis being the most common features. The diagnosis may be difficult to attain, but family history is one of the most important steps in workup, in addition to the radiographic identification of skeletal changes.
The clinical presentation of patients with spondylometaphyseal dysplasia (SMD) starts as early as infancy and involves various skeletal abnormalities, but the axial skeleton - the rib cage and the spine, and the metaphyses of femoral bones, but also the iliac bones are principally affected . Flattened vertebral bodies (platyspondyly), congenital scoliosis, dysplasia of the ribs, iliac and proximal femur (frequently ending in development of coxa vara) are main manifestations of SMD  , followed by postnatal growth failure and short stature that is evident from early childhood, progressive lower-limb bowing, and a fragmented appearance of metaphyses (known as "corner fractures") . Moreover, impaired growth causes hypoplasia of the rib cage due to shortening of the ribs, which can create respiratory problems of varying severity, but an increased susceptibility to infections is frequently documented . In some patients, retinal changes, such as retinitis pigmentosa, pigmentary retinal degeneration or cone-rod dystrophy, appear in early childhood and can lead to visual impairment, mainly affecting visual acuity  .
Entire Body System
It usually starts in early childhood when poor growth with uneven stature and a waddling gait with bow legs (genu varum) is noticed. Early osteoarthritis of the joints is also common. [rarediseases.info.nih.gov]
Patients come for poor growth, problems with walking or joint pains, but rarely before 2 years of age. Diagnosis is radiographic. Ossification centers are late in appearance, small and irregularly mineralised. [orthopaedicsone.com]
Increased Susceptibility to Infections
Moreover, impaired growth causes hypoplasia of the rib cage due to shortening of the ribs, which can create respiratory problems of varying severity, but an increased susceptibility to infections is frequently documented. [symptoma.com]
The findings demonstrate that mutations in TRPV4 produce a phenotypic spectrum of skeletal dysplasias from the mild autosomal-dominant brachyolmia to SMDK to autosomal-dominant metatropic dysplasia, suggesting that these disorders should be grouped into [ncbi.nlm.nih.gov]
Title Other Names: Dysmorphism arthrogryposis skeletal maturation advanced; Jequier-Kozlowski syndrome; Skeletal dysplasia Jequier-Kozlowski type; Dysmorphism arthrogryposis skeletal maturation advanced; Jequier-Kozlowski syndrome; Skeletal dysplasia [rarediseases.info.nih.gov]
Pathogenic variants in TRPV4 are known to cause both a spectrum of skeletal dysplasias and neuropathies. [karger.com]
[…] short stature Disproportionate short-trunked dwarfism Disproportionate short-trunked short stature Short-trunked dwarfism [ more ] 0003521 Flat acetabular roof 0003180 Irregular acetabular roof 0008833 Irregular, rachitic-like metaphyses 0005042 Kyphoscoliosis [rarediseases.info.nih.gov]
Based on our observations and Isidor's report, the clinical and radiological hallmarks of axial SMD can be defined: The main clinical findings are postnatal growth failure, rhizomelic short stature in early childhood evolving into short trunk in late [ncbi.nlm.nih.gov]
Photographs of the second sibling pair showing (A) short-trunk dwarfism, (B) compressed root of the nose, and (C) genu valgum. [healio.com]
Symptoms & Signs Characteristic symptoms resemble those of spondyloepiphyseal dysplasia, congenital type which include: short stature evident from birth, short trunk & shortened limbs. [signssymptoms.org]
Symptoms and Signs Characteristic symptoms resemble those of spondyloepiphyseal dysplasia, congenital type which include: short stature evident from birth, short trunk and shortened limbs. [medigest.uk]
Limited joint mobility Limited joint motion [ more ] 0001376 Pectus carinatum Pigeon chest 0000768 Scoliosis Abnormal curving of the spine 0002650 Short neck Decreased length of neck 0000470 5%-29% of people have these symptoms Abnormality of epiphysis [rarediseases.info.nih.gov]
Other signs and symptoms include small hands and fingers, spine deformities, and X-ray showing short vertebra, mild metaphyseal changes, severe delay in ossification, square, short, flared iliac wings (the broadest part of the pelvic bone) and a flat [rarediseases.info.nih.gov]
Face, Head & Neck
neck Decreased length of neck 0000470 5%-29% of people have these symptoms Abnormality of epiphysis morphology Abnormal shape of end part of bone 0005930 Aplastic clavicle Absent collarbone 0006660 Hypoplasia of the odontoid process 0003311 Narrow chest [rarediseases.info.nih.gov]
Affiliated tissues include bone, and related phenotypes are low-set ears and short neck [malacards.org]
Soon after birth he had lowhairline, mild hypertelorism, short neck, frontal bossing, retrognathia, broad hands, and short limbs. [cags.org.ae]
TAS OMIM:250220 HPO:probinson 17.02.2009 OMIM:250220 SPONDYLOMETAPHYSEAL DYSPLASIA, SEDAGHATIAN TYPE HP:0000425 Flattened nasal bridge TAS TAS OMIM:250220 HPO:probinson 17.02.2009 OMIM:250220 SPONDYLOMETAPHYSEAL DYSPLASIA, SEDAGHATIAN TYPE HP:0000470 Short [sourceforge.net]
[ more ] 0002750 Depressed nasal bridge Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ] 0005280 Enlarged joints 0003037 Genu valgum Knock knees 0002857 High [rarediseases.info.nih.gov]
Low Nasal Root
nasal root [ more ] 0005280 Enlarged joints 0003037 Genu valgum Knock knees 0002857 High forehead 0000348 Kyphosis Hunched back Round back [ more ] 0002808 Limitation of joint mobility Decreased joint mobility Decreased mobility of joints Limited joint [rarediseases.info.nih.gov]
Depressed Nasal Bridge
nasal bridge Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ] 0005280 Enlarged joints 0003037 Genu valgum Knock knees 0002857 High forehead 0000348 Kyphosis [rarediseases.info.nih.gov]
gait 'Waddling' gait Waddling walk [ more ] 0002515 Showing of 34 Last updated: 5/1/2019 If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. [rarediseases.info.nih.gov]
gait Causes - Spondylometaphyseal dysplasia- X-linked * Breathing problems * Coarse facial appearance * Flat nose bridge * Flattened vertebrae * Mental retardation * Short stature * Speech impairment * Strabismus * Waddling gait * Wide-set eyes Prevention [checkorphan.org]
gait Associated Genes FN1 (Withdrawn symbols: CIG, FINC, GFND2, LETS, MSF ) Mouse Orthologs Fn1 (Withdrawn symbols: Fn-1 ) Source OMIM:184255 (names, synonyms, disease associated genes), Orphanet (disease classes), HGNC, Ensembl, MGI (gene symbols, gene [mousephenotype.org]
Clinically, the symptoms include a waddling gait, limb length discrepancy and frequent weariness. Developmental coxa vara is sometimes associated with skeletal dysplasia. [synapse.koreamed.org]
The patient was able to walk at 11 months of age,but had a“waddling gait”. [webview.isho.jp]
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, et al: Fetal akinesia in metatropic dysplasia: the combined phenotype of chondrodysplasia and neuropathy? Am J Med Genet A 155A:2860-2864 (2011). [karger.com]
He still had a disturbed gait, but was otherwise well. His length was 84.5 cm (below the 3 rd centile); The upper segment was 48.5 cm, and the lower segment 46 cm. Radiographs showed severe coxa vara and mild dysplasia of the spine. [czytelniamedyczna.pl]
Having in mind the fact that the vast majority of cases appear in a familial fashion, a detailed patient history can reveal the presence of symptoms in siblings or first-degree relatives, thus confirming clinical suspicion toward inherited diseases. In fact, parental consanguinity has been reported in some cases . A carefully performed physical examination is the next step in workup, which should note visual impairment and signs of reduced growth and scoliosis, as well as thoracic hypoplasia. Imaging studies, primarily in the form of radiography, are used to describe the changes seen in SMD, most important being cupped and flared anterior end of ribs, mild spondylar dysplasia, serrated iliac crests, and metaphyseal dysplasia involving the proximal femur  . Although the genetic basis of the disease remains incompletely understood, whole-genome sequencing has revealed mutations in chromosome 21 open reading frame 2 (C21orf2) and choline phosphate cytidyltransferase A (PCYT1A) genes, suggesting that their detection may be helpful in distinguishing the diagnosis from more than 40 other skeletal disorder groups that have a similar clinical presentation and background  . Other reports, however, have evaluated the presence of mutations in the collagen 2 alpha 1 (COL2A1) gene and parathyroid hormone 1 receptor (PTH1R) , but clear genetic markers are yet to be defined, and the diagnosis frequently rests on radiographic and clinical criteria. Magnetic resonance imaging (MRI) can be used for detecting spinal abnormalities. Moreover, other imaging techniques like hip arthrography, computed tomography (CT) may also be employed for the diagnosis of the disease.
- Wang Z, Iida A, Miyake N, et al. Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations. Janecke AR, ed. PLoS ONE. 2016;11(3):e0150555.
- Sutton VR, Hyland JC, Phillips WA, Schlesinger AE, Brill PW. A dominantly inherited spondylometaphyseal dysplasia with "corner fractures" and congenital scoliosis. Am J Med Genet A. 2005;133A(2):209-212.
- Yamamoto GL, Baratela WAR, Almeida TF, et al. Mutations in PCYT1A Cause Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy. Am J of Hum Genet. 2014;94(1):113-119.
- Suzuki S, Kim OH, Makita Y, et al. Axial spondylometaphyseal dysplasia: additional reports. Am J Med Genet A. 2011;155A(10):2521-2528.
- Czarny-Ratajczak M1, Chrzanowska K, Bieganski T, Sulko J, Baranska D. Severe neonatal spondylometaphyseal dysplasia in two siblings. Am J Med Genet A. 2009;149A(10):2166-72.