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Spondylometaphyseal Dysplasia

Spondylometaphyseal Dysplasia, Kozlowski Type

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.


Presentation

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
  • face pelvic scapula dysplasia Short stature heart defect craniofacial anomalies Short stature hyperkaliemia acidosis Short stature locking fingers Short stature mental retardation eye anomalies Short stature mental retardation eye defects Short stature[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]
Skeletal Dysplasia
  • Spondylometaphyseal dysplasia corner fracture type (Sutcliffe) is an uncommon form of skeletal dysplasia which has some unique imaging features.[ncbi.nlm.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]
  • We present a previously undescribed skeletal dysplasia characterized by mild platyspondyly, small thorax with cupping of the anterior ends of the ribs, irregular proximal femoral metaphyses, and lacy appearance of the iliac wings.[ncbi.nlm.nih.gov]
  • Metaphyseal dysplasia, type Jansen (JMD), is a rare skeletal dysplasia with characteristic radiographic abnormalities. Of the various types of metaphyseal dysplasia, JMD shows the most severe alteration in metaphyseal architecture.[ncbi.nlm.nih.gov]
  • 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]
Trunk Shortness
  • 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]
  • Case 24 showed short femoral necks and scoliosis as a child, but also developed joint laxity, dysmorphic features and a short limb short stature instead of a short trunk short stature.[ojrd.biomedcentral.com]
Short Neck
  • Soon after birth he had lowhairline, mild hypertelorism, short neck, frontal bossing, retrognathia, broad hands, and short limbs.[cags.org.ae]
  • 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]
  • neck of thighbone 0100864 Short stature Decreased body height Small stature [ more ] 0004322 Spondylometaphyseal dysplasia 0002657 Showing of 29 Last updated: 11/1/2018 There is no specific treatment for axial spondylometaphyseal dysplasia.[rarediseases.info.nih.gov]
  • Soon after birth hehad low hairline, mild hypertelorism, short neck, fron-tal bossing, retrognathia, broad hands, and shortlimbs. His upper to lower body segment ratio was 1.5:1.0. The eyes were normal and so were nose, palate,lips, and philtrum.[vdocuments.net]
  • 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]
Tremor
  • 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]
Cognitive Defect
  • 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]

Workup

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.

Treatment

  • The patient developed a main thoracic scoliosis that did not require additional treatment.[ncbi.nlm.nih.gov]
  • This article reports the dental treatment and oral findings of a 14-year-old female patient with Kozlowski dwarfism.[ncbi.nlm.nih.gov]
  • Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.[ncbi.nlm.nih.gov]
  • We are unaware of any cases describing the use of growth hormone therapies for treatment of short stature caused by axial spondylometaphyseal dysplasia. Treatment of skeletal dysplasias with growth hormone therapy must be done with caution.[rarediseases.info.nih.gov]
  • There are only a few treatments available for the improvement of motor function in stroke patients. The majority of these treatments a... ConclusionsLamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy.[medworm.com]

Prognosis

  • 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

  • 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 Etiology remains unknown. Genetic counseling Autosomal recessive inheritance has been suggested. Last updated: 9/30/2009[rarediseases.info.nih.gov]
  • Etiology Autosomal dominant inheritance has been suggested, but the causative gene has not yet been identified. Last updated: 11/15/2009 This table lists symptoms that people with this disease may have.[rarediseases.info.nih.gov]

Epidemiology

  • Epidemiology Nine cases have been reported so far in patients of Iranian, Yemeni and Caucasian origin.[rarediseases.info.nih.gov]
  • Epidemiology This condition has been reported in five members of an Algerian family and one Polish boy; the patient reported by Schmidt et al. possibly had this disorder.[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]
  • (August 2017) History and epidemiology [ edit ] The disorder was first described by Jonathan Zonana and associates in 1977. [1] Further observation of four cases of it was reported by Pierre Maroteaux and colleagues in 1982, [14] and Maroteaux was the[en.wikipedia.org]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • 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]
  • 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]

Prevention

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

References

Article

  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.

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Last updated: 2018-06-21 19:22