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Spondylometaphyseal Dysplasia Type Kozlowski 

SMD Kozlowski

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[wikidoc.org]
  • 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]
Asymptomatic
  • A girl with Kozlowski's spondylometaphyseal dysplasia and asymptomatic hypocalciuric hypercalcemia, a previously unrecognised association, is described.[ncbi.nlm.nih.gov]
  • During the course of NICU stay, baby remained asymptomatic and was treated for gastro-esophageal reflux. On chest X-ray obtained as part of apnea, workup showed metaphyseal widening and dysplasia.[mjdrdypu.org]
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]
Limited Mobility
  • 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]
Macula
  • Dilated ocular fundus examination revealed similar appearing bilateral, large, excavated, well-circumscribed oval areas of chorioretinal atrophy occupying the macula between the aracades.[ncbi.nlm.nih.gov]
  • The macula and OCT have been reported as normal. Telecanthus, nystagmus, hypertelorism, proptosis, and photophobia have been reported. Early onset and progressive visual impairment are characteristic.[disorders.eyes.arizona.edu]
Visual Impairment
  • 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.[symptoma.com]
  • Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod[ncbi.nlm.nih.gov]
  • Early onset and progressive visual impairment are characteristic. Systemic Features: Only 5 patients with this condition have been reported most of whom were short in stature. There may be frontal bossing and the chest is narrow and flattened.[disorders.eyes.arizona.edu]
  • It is thought to be inherited in an autosomal recessive fashion. 0002750 Platyspondyly Flattened vertebrae 0000926 Rhizomelia Disproportionately short upper portion of limb 0008905 Rod-cone dystrophy 0000510 Visual impairment Impaired vision Loss of eyesight[rarediseases.info.nih.gov]
Ectopia Lentis
  • Lentis Kozlowski Tsuruta Taki Syndrome Langer Mesomelic Dysplasia Laplane Fontaine Lagardere Syndrome Larsen Syndromes Leri-Weill dyschondrosteosis Lethal Chondrodysplasia with Long Bone Angulation and Mixed Bone Density Leukoencephalopathy with Metaphyseal[rgd.mcw.edu]
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]
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]
Joint Limitation
  • 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]
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 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]
  • 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]
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: 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 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,[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]
  • Discussion SMDST is characterized clinically by short stature and a waddling gait.[czytelniamedyczna.pl]
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

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]

Epidemiology

  • Epidemiology Nine cases have been reported so far in patients of Iranian, Yemeni and Caucasian origin.[rarediseases.info.nih.gov]
  • 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]
  • 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]
  • You can help by adding to it . ( 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[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: 2019-07-11 20:15