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 [1]. 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 [2] [3], 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") [2]. 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 [4]. 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 [1] [4].

• Dysmorphic Face

  […] polysyndactyly Short s Short stature abnormal skin pigmentation mental retardation Short stature Brussels type Short stature contractures hypotonia Short stature cranial hyperostosis hepatomegaly Short stature deafness neutrophil dysfunction Short stature dysmorphic [ipfs.io]

  face pelvic scapula dysplasia Short stature hyperkaliemia acidosis Short stature mental retardation eye anomalies Short stature microcephaly seizures deafness Short stature monodactylous ectrodactyly cleft palate Short stature prognathism short femoral [personalizedcause.com]

• Short Trunk

  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]

• Genu Valgum

  Heritability: Autosomal dominant inheritance AKA: Spondylometaphyseal Dysplasia With Severe Genu Valgum, Spondylometaphyseal dysplasia, Algerian type, Spondylometaphyseal dysplasia with severe genu valgum, Spondylometaphyseal Dysplasia, Schmidt Type, [monarchinitiative.org]

  Title Other Names: Spondylometaphyseal dysplasia Schmidt type; Spondylometaphyseal dysplasia with severe genu valgum; Schmid metaphyseal dysostosis; Spondylometaphyseal dysplasia Schmidt type; Spondylometaphyseal dysplasia with severe genu valgum; Schmid [rarediseases.info.nih.gov]

  Individuals with SMD-A manifest with short trunk and severe genu valgum. Myopia may be a syndromic component. [karger.com]

  Photographs of the second sibling pair showing (A) short-trunk dwarfism, (B) compressed root of the nose, and (C) genu valgum. [healio.com]

  […] vision due to myopia or retinal detachment hip pain due to coxa varus decreased walking distance due to poor muscular endurance and skeletal deformities Physical exam inspection short stature flatened facies kyphoscoliosis lumbar lordosis coxa vara genu [orthobullets.com]

• Severe Short Stature

  He presented with postnatal severe short stature, progressive lower limb deformity with rhizomelic shortening of the long bones, prominent joints with limited mobility in knees and elbows, mild thoracic scoliosis, and vision impairment due to cone dystrophy [ncbi.nlm.nih.gov]

  short stature Dwarfism Proportionate dwarfism Short stature, severe [ more ] 0003510 Short sacroiliac notch 0003185 Short tubular bones of the hand 0001248 Tibial metaphyseal irregularity 0030292 Showing of 24 | Last updated: 5/1/2019 If you need medical [rarediseases.info.nih.gov]

• Decrease in Height

  […] body height Small stature [ more ] 0004322 Spondylometaphyseal dysplasia 0002657 30%-79% of people have these symptoms Hypoplastic pelvis 0008839 Joint dislocation Joint dislocations Recurrent joint dislocations [ more ] 0001373 Platyspondyly Flattened [rarediseases.info.nih.gov]

• Chest Deformity

  […] including kidney, lungs, heart, liver, GI tract Chest deformity Misshapen, fused or absent ribs Breathing difficulties Short stature (dwarfism) Abnormal growth of arms and legs Hand and foot anomalies Vision and hearing impairments Skin abnormalities [chop.edu]

• Short Neck

  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]

  neck TAS TAS OMIM:250220 HPO:probinson 17.02.2009 OMIM:250220 SPONDYLOMETAPHYSEAL DYSPLASIA, SEDAGHATIAN TYPE HP:0000773 Short ribs TAS TAS OMIM:250220 HPO:probinson 17.02.2009 OMIM:250220 SPONDYLOMETAPHYSEAL DYSPLASIA, SEDAGHATIAN TYPE HP:0000774 Narrow [sourceforge.net]

  […] stature Decreased body height Small stature [ more ] 0004322 Short thorax Shorter than typical length between neck and abdomen 0010306 Spondylometaphyseal dysplasia 0002657 30%-79% of people have these symptoms Brachydactyly Short fingers or toes 0001156 [rarediseases.info.nih.gov]

  neck with restricted mobility and pain Organ abnormalities including kidney, lungs, heart, liver, GI tract Chest deformity Misshapen, fused or absent ribs Breathing difficulties Short stature (dwarfism) Abnormal growth of arms and legs Hand and foot [chop.edu]

• Waddling Gait

  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 'Waddling' gait Waddling walk [ more ] 0002515 Showing of 34 | Last updated: 2/1/2021 Find a Specialist Find a Specialist 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 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]

• Ataxia

  ataxia 3 Spinocerebellar ataxia 30 Spinocerebellar ataxia 31 Spinocerebellar ataxia 4 Spinocerebellar ataxia 5 Spinocerebellar ataxia 6 Spinocerebellar ataxia 7 Spinocerebellar ataxia 8 Spinocerebellar ataxia 9 Spinocerebellar ataxia autosomal recessive [personalizedcause.com]

  (multiple types) Spinocerebellar ataxia amyotrophy deafness Spinocerebellar ataxia dysmorphism Spinocerebellar atrophy type 3 Spinocerebellar degeneration corneal dystrophy Spinocerebellar degenerescence book type Spir Spirochetes disease Spirurida infections [ipfs.io]

  (multiple types) Spinocerebellar ataxia amyotrophy deafness Spinocerebellar ataxia dysmorphism Spinocerebellar atrophy type 3 Spinocerebellar degeneration corneal dystrophy Spinocerebellar degenerescence book type Spir Spirochetes disease Spirurida Infections [wikidoc.org]

  In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension [ncbi.nlm.nih.gov]

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 [1]. 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 [1] [4]. 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 [1] [3]. Other reports, however, have evaluated the presence of mutations in the collagen 2 alpha 1 (COL2A1) gene and parathyroid hormone 1 receptor (PTH1R) [5], 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.

• Delayed Bone Age

  The typical radiographic features are platyspondyly and medially placed vertebral pedicles in the spine; metaphyseal irregularities, especially in the proximal femur; abnormal acetabula and delayed carpal bone age [ 5 ]. [ojrd.biomedcentral.com]

Treatment Treatment Options: No effective treatment is known. [disorders.eyes.arizona.edu]

This article reports the dental treatment and oral findings of a 14-year-old female patient with Kozlowski dwarfism. [ncbi.nlm.nih.gov]

There is a study titled Evaluation and Treatment of Skeletal Diseases which may be of interest to you. [rarediseases.info.nih.gov]

Prognosis - Spondylometaphyseal dysplasia- X-linked Not supplied. Treatment - Spondylometaphyseal dysplasia- X-linked Not supplied. Resources - Spondylometaphyseal dysplasia- X-linked Not supplied. [checkorphan.org]

The nature of their genetic condition and any other health issues, how quickly the child is diagnosed, and possible treatment options, all factor into a child’s long-term prognosis. [chop.edu]

Prognosis SED is nonlethal, and life expectancy is not reduced. However, morbidity is increased, and regular monitoring and follow-up care should be encouraged. [emedicine.medscape.com]

Because of this frequency and the diversity of these conditions, it is essential that the practitioner be able to recognize a fetus, newborn, or child with a skeletal dysplasia so that the diagnosis can be established, the prognosis determined, and a [musculoskeletalkey.com]

Etiology Etiology remains unknown. Genetic counseling Autosomal recessive inheritance has been suggested. Last updated: 9/30/2009 [rarediseases.info.nih.gov]

We want to emphasize that in this rare congenital lethal skeletal dysplasia with unknown etiology, central nervous system malformations might be a major component of the disorder and should be evaluated in detail to possibly uncover the underlying pathophysiology [ncbi.nlm.nih.gov]

Etiology Kozlowski type of spondylometaphyseal dysplasia results in severe kyphoscoliosis and is caused by mutations in the TRPV4 gene (locus 12q24.1). [orpha.net]

Summary Epidemiology Prevalence is estimated at around 1/100,000. Clinical description The disorders are characterized by platyspondyly (flattened vertebrae) and marked hip and knee metaphyseal lesions. [orpha.net]

Epidemiology Nine cases have been reported so far in patients of Iranian, Yemeni and Caucasian origin. [rarediseases.info.nih.gov]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.es]

Introduction A form of short-trunk dwarfism caused by a defect in the secondary ossification center (epiphysis) Epidemiology rare Pathophysiology caused by abnormal synthesis of Type II collagen primarily affects the vertebrae and epiphysis of bone Genetics [orthobullets.com]

We want to emphasize that in this rare congenital lethal skeletal dysplasia with unknown etiology, central nervous system malformations might be a major component of the disorder and should be evaluated in detail to possibly uncover the underlying pathophysiology [ncbi.nlm.nih.gov]

Introduction A form of short-trunk dwarfism caused by a defect in the secondary ossification center (epiphysis) Epidemiology rare Pathophysiology caused by abnormal synthesis of Type II collagen primarily affects the vertebrae and epiphysis of bone Genetics [orthobullets.com]

The pathophysiology of Pyle metaphyseal dysplasia is a defect in metaphyseal remodeling which leads to metaphyseal widening of the long tubular bones with associated cortical thinning and osteoporosis. [mjdrdypu.org]

Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). [genecards.org]

Waddling 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]

Nausea, vomiting Acrokeratoelastoidosis of Costa Popularity City, USA Tag Clobetasol, popularity Tucson generic clobetasol 15g 5 cream with amex 26247 Stockton buy clobetasol australia 36384 Upset stomach, preventing skin infections, use as a source of [annies.com]

Studies have shown that individuals who have more severe mutations (for example, premature stop codons or a substitution of a glycine) that prevent a pro-alpha 1 or a pro-alpha 2 chain from being formed typically have a milder form of OI (OI type I or [musculoskeletalkey.com]

1. 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.
2. 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.
3. 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.
4. Suzuki S, Kim OH, Makita Y, et al. Axial spondylometaphyseal dysplasia: additional reports. Am J Med Genet A. 2011;155A(10):2521-2528.
5. 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.