Spondylo-Epi-Metaphyseal Dysplasia (SEMD) Matrilin 3 Type

Total Page:16

File Type:pdf, Size:1020Kb

Spondylo-Epi-Metaphyseal Dysplasia (SEMD) Matrilin 3 Type 366 LETTER TO JMG Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of J Med Genet: first published as on 30 April 2004. Downloaded from SEMD Z U Borochowitz*, D Scheffer*, V Adir, N Dagoneau, A Munnich, V Cormier-Daire ............................................................................................................................... J Med Genet 2004;41:366–372. doi: 10.1136/jmg.2003.013342 steochondrodysplasia is a heterogeneous group of Key points conditions caused by impaired development of oss- Oeous skeleton. Within this group, spondylo-epi- metaphyseal dysplasia (SEMD) represents a subgroup which N We investigated a large consanguineous Arabic- includes a number of conditions associated with vertebral, Muslim family in which five affected individuals were epiphyseal, and metaphyseal anomalies. The International diagnosed with a novel form of autosomal recessive Classification recognises at least 15 distinct entities within spondylo-epi-metaphyseal dysplasia (SEMD). All five this group as defined by a combination of clinical, radi- affected individuals presented with disproportionate ological, and molecular data.1 Mutations in the genes early-onset dwarfism, bowing of the lower limbs, encoding structural proteins of the cartilage extracellular lumbar lordosis, and normal hands. Skeletal findings matrix (that is, cartilage oligomeric matrix protein, type II included short, wide, and stocky long bones with collagen, perlecan) or involved in posttranslational process- severe epiphyseal and metaphyseal changes, hypo- ing and transport (lysosomal storage disorders, sulfation plastic iliac bones, and flat-ovoid vertebral bodies. protein (PAPSS2), regulator of chromatin (SMARCAL1), N Genome wide homozygosity mapping mapped the transcription initiation factor kinase (EIFKA3)) have been disease locus gene to chromosome 2p25–24 with a previously shown to be responsible for different forms of SEMD.1–6 However, a large number of SEMD conditions are maximum LOD score of 3.46 at locus D2S305. Two still defined on purely descriptive features. Here, we describe recombination events defined the minimal critical http://jmg.bmj.com/ five patients from a large consanguineous family of Arabic- region interval between loci D2S320 and D2S215 Muslim origin with short-limb dwarfism with distinct (2.24 Mb). Using a candidate gene approach, we skeletal dysplasia which, to our knowledge, has not been identified, in all affected individuals, a homozygous described previously. The manifestations and a constellation substitution (973T.A)inthegeneencodingfor of radiographic bony abnormalities are unique in this entity. Matrilin 3 (MATN3), a cartilage specific protein. The As there are abnormalities in the vertebral bodies, long bones, mutations changed a cysteine into a serine in the EGF- and specifically the lower limbs involving epiphyses and domain of MATN3, in a region highly conserved on September 29, 2021 by guest. Protected copyright. metaphyses, we suggest that this entity be called spondylo- across species. epi-metaphyseal dysplasia, bowed-legs type. This hitherto N We conclude that homozygous MATN3 mutations are unreported form of autosomal recessive SEMD is caused by responsible for this novel form of SEMD. homozygous mutation in matrilin 3 (MATN3), a component of the extracellular matrix of cartilage. This finding not only provides a molecular explanation for a novel form of SEMD but also expands the phenotype range of MATN3 defects legs, waddling gait, wide joints (especially the knees), with which have been previously identified in autosomal limited elbow extension, pectus excavatum, and lumbar dominant epiphyseal dysplasia and idiopathic hand osteo- lordosis. At age 10 years, she underwent bilateral osteotomy 78 arthritis. of both proximal tibiae due to severe bowing. Examination at age 12 years showed the same changes (height at -4 SD), METHODS severe waddling gait, and very pronounced bowing of lower In this family, five affected individuals were found to have limbs. disproportionate dwarfism with similar clinical and radi- Patient 2, the brother of the propositus (figs 1 and 2), had ological features. Patient 1 (figs 1 and 2) was born to healthy short limbs at birth (length 45 cm (-2 SD), head circumfer- parents of Arabic-Muslim origin who are first cousins and of ence 34 cm). At 4 months, he had bowed lower legs, and normal stature (father 175 cm (75th centile) and mother mild lumbar lordosis (length 55 cm, -3 SD). On follow-up, he 168 cm (50th centile)), after a term pregnancy and normal was noted to have short limbs, severe short stature, small delivery (birth weight 3100 g, birth length 45 cm (-2 SD), chest, lumbar lordosis, and waddling gait. No hyperlaxity of head circumference 33 cm). At 1 year, she had short-limbed joints was noted. short stature (height 68 cm (-3 SD), weight 8 kg (3rd Patient 3 is the second brother of the propositus (fig 1). At centile), head circumference 43 cm (-3 SD), arm span 33 weeks of gestation, ultrasound had detected short limbs. 71 cm, palm length 5.2 cm (50th centile), middle finger length 3.2 cm (3rd centile)). Neurological examination, psychomotor development, hearing, and visual acuity were Abbreviations: ACFD, acrocapital femoral dysplasia; BDA1, brachydactyly type A1; LAPTM4A, lysosomal-associated protein otherwise normal. Routine chemistry, thyroid function tests, transmembrane 4; MATN3, matrilin 3; MED, multiple epiphyseal and renal ultrasounds were normal as well. Re-evaluation at dysplasia; OA, osteoarthritis; SEMD, spondylo-epi-metaphyseal 6 years showed further disproportion of limbs, with bowed dysplasia www.jmedgenet.com Letter to JMG 367 J Med Genet: first published as on 30 April 2004. Downloaded from Figure 1 Pedigree of the family and genotype analysis of eight markers within the linked region on chromosome 2. http://jmg.bmj.com/ on September 29, 2021 by guest. Protected copyright. Figure 2 Patients 1 and 2: total AP and lateral view of the body. Note the short trunk and severe bowing of legs. www.jmedgenet.com 368 Letter to JMG He was delivered normally at 39 weeks and examination at hands were normal. The iliac wings were dysplastic and birth showed short limbs (length 44 cm (-2 SD), head square with narrowing of the greater sciatic notch. The circumference 33 cm). Recent examination at 4 months acetabular roof was flat, projecting medially from the roof showed short limbs and bowed thighs. No chest narrowing with a bony spike, giving rise to a trident configuration of the or joint hyperlaxity was noted. iliac bone. The pubic bones were hypoplastic with small and Patient 4, the brother of the father of the propositus (fig 1), underossified ischia. Epiphyseal and metaphyseal changes as was born to parents who were first cousins. He was first well as spinal changes increased in severity with time J Med Genet: first published as on 30 April 2004. Downloaded from examined at 23 years of age (head circumference 52.5 cm (fig 3B,D). (-2.5 SD), height 136 cm (-5 SD), arm span 147 cm, palm It should be emphasised that in the family reported here, length 11 cm (90th centile), middle finger length 7.6 cm none of the obligate heterozygote parents or the carrier (50th centile)). He had a waddling gait since he started healthy sib sister of the propositus (fig 1) ever complained of walking (at 1 year), short limbs with severe short stature, knee or hip pain or hand osteoarthritis or underwent surgery bowing of lower limbs, and severe lumbar lordosis. At 13 for early-onset osteoarthritis. A complete skeletal radio- years of age, he underwent bilateral osteotomy of both graphic evaluation of the propositus’ parents as adults, and proximal tibiae for severe bowing. On follow-up at age 32, he of the healthy sib sister as a teenager, did not reveal any is married with four children, all with regular height. skeletal changes or any epiphyseal dysplasia. Patient 5 is the half-cousin of the propositus (fig 1). He Approval was obtained from the National Helsinki was born to parents who were first cousins after a 41 week Committee for Genetic Research in Humans, and informed pregnancy (birth weight 3000 g). Waddling gait was noted consent was given by family members or parents of the when he began walking at approximately 1 year of age. At affected minors. Homozygosity mapping of the disease gene age 11.5 years, he had short-limbed short stature (height of was performed using a panel of 400 markers at an average 117 cm (-4 SD), head circumference 51 cm (10th centile), distance of 10 cM. Genomic DNA was extracted from arm span 122 cm, palm length 5.2 cm (50th centile), middle leukocytes according to standard procedures. The MLINK finger length 3.2 cm (3rd centile)). He had a flat face, normal program of the linkage software package was used to shaped chest, short limbs, hyperlordosis of the lumbar area, calculate two-point LOD scores between the disease pheno- wide joints, with limited extension of elbows, and bowed type and each of the markers, assuming a recessive disease lower limbs. On follow-up at age 23 years (height 130 cm), with an allele frequency of 0.001. the same clinical features were noted. He conducted a normal A series of 18 primers was used to amplify the eight coding life and drove a car. exons of the MATN3 gene (including intron–exon bound- x Ray radiographs of patient 3 at birth were similar to those aries) as previously described.7 at 3 months (fig 3A) and showed ribs of normal length, with Amplified products were purified and sequenced using the posteriorly marked cupping. In the lateral projection, most of fluorescent dideoxyterminator method on an ABI 3100 the vertebral bodies had an oval shape. In the AP projection, automatic sequencer. http://jmg.bmj.com/ vertebral bodies were flat. The long tubular limb bones (except those of the hands and feet) were abnormally short with a stocky appearance and relatively wide metaphyses RESULTS with lateral spurs.
Recommended publications
  • Metaphyseal Dysplasia: a Rare Case Report Dildip Khanal* Karuna Foundation Nepal “Saving Children from Disability, One by One”, Nepal
    ical C lin as Khanal, J Clin Case Rep 2016, 6:2 C e f R o l e a p DOI: 10.4172/2165-7920.1000726 n o r r t u s o J Journal of Clinical Case Reports ISSN: 2165-7920 Case Report Open Access Metaphyseal Dysplasia: A Rare Case Report Dildip Khanal* Karuna Foundation Nepal “Saving Children from Disability, One by One”, Nepal Abstract Metaphyseal dysplasia is a very rare inherited bone disorder. Here is a case report and possible treatment options for 11 years old child, detected by Karuna foundation Nepal. Keywords: Metaphyseal dysplasia; Pyle; Therapeutic rehabilitation; Karuna foundation Nepal Background Metaphyseal dysplasia also known as Pyle disease is a heterogeneous group of disorders, characterized by the metaphyseal changes of the tubular bones with normal epiphyses. The disease was described briefly by Pyle in 1931 [1,2]. Incidence occurs at a rate of two to three newborns per 10,000 births involving the proliferative and hypertrophic zone of Figure 1: Bilateral genu varum deformity. the physis (epiphysis is normal). Jansen, Schmid and McKusick are the three sub-types with a few reports worldwide [3-9]. Karuna foundation Nepal (KFN) is a non-governmental organization which believes in a world in which each individual, with or without disabilities, has equal access to good quality health care, can lead a dignified life, and can participate as much as possible in community life. KFN approach is entrepreneurial and action oriented, working towards setting up and strengthening existing local health care system, stimulating community participation and responsibility- including health promotion, prevention and rehabilitation through Figure 2: Flat foot.
    [Show full text]
  • A Case Report of Dysosteosclerosis Observed from the Prenatal Period
    Clin Pediatr Endocrinol 2010; 19(3), 57-62 Copyright© 2010 by The Japanese Society for Pediatric Endocrinology Case Report A Case Report of Dysosteosclerosis Observed from the Prenatal Period Kisho Kobayashi1, 2, Yusuke Goto1, 2, Hiroaki Kise1, 2, Hiroaki Kanai1, 2, Koji Kodera1, 2, Gen Nishimura3, Kenji Ohyama1, Kanji Sugita1, and Takayuki Komai1, 2 1Department of Pediatrics, University of Yamanashi, Yamanashi, Japan 2Department of Pediatrics, Yamanashi Prefectural Central Hospital, Yamanashi, Japan 3Department of Radiology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan Abstract. Dysosteosclerosis is a sclerosing bone dysplasia with skeletal changes resembling those of osteopetrosis. The disorder is associated with dental anomalies and occasionally mental retardation. Because of the rarity and phenotypic diversity of dysosteosclerosis, it remains unsolved whether or not the disorder is heterogeneous. We report here on an affected boy associated with brain calcification and epilepsy with developmental delay. Prenatal ultrasound revealed ventriculomegaly, and brain CT in the neonatal period showed periventricular calcifications. At 13 mo of age, he presented with generalized convulsion with developmental delay. Metaphyseal sclerosis, metaphyseal undermodeling, and oval-shaped vertebral bodies on skeletal survey warranted a diagnosis of dysosteosclerosis. Retrospective review of radiographs as a neonate showed metaphyseal radiolucency, but not metaphyseal sclerosis. Since then, neither the bone changes nor neurological symptom has progressively worsened up to 4 yr of age. Thus, it is thought that the clinical and radiological manifestations of the sclerotic disorder become obvious during infancy. Brain calcification of prenatal onset may be an essential syndromic constituent of the disorder. Key words: dysosteosclerosis, metaphyseal sclerosis, congenital bone disease, periventricular calcification Introduction compression resulting in certain manifestations, such as blindness and facial paralysis.
    [Show full text]
  • Blueprint Genetics Comprehensive Skeletal Dysplasias and Disorders
    Comprehensive Skeletal Dysplasias and Disorders Panel Test code: MA3301 Is a 251 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of disorders involving the skeletal system. About Comprehensive Skeletal Dysplasias and Disorders This panel covers a broad spectrum of skeletal disorders including common and rare skeletal dysplasias (eg. achondroplasia, COL2A1 related dysplasias, diastrophic dysplasia, various types of spondylo-metaphyseal dysplasias), various ciliopathies with skeletal involvement (eg. short rib-polydactylies, asphyxiating thoracic dysplasia dysplasias and Ellis-van Creveld syndrome), various subtypes of osteogenesis imperfecta, campomelic dysplasia, slender bone dysplasias, dysplasias with multiple joint dislocations, chondrodysplasia punctata group of disorders, neonatal osteosclerotic dysplasias, osteopetrosis and related disorders, abnormal mineralization group of disorders (eg hypopohosphatasia), osteolysis group of disorders, disorders with disorganized development of skeletal components, overgrowth syndromes with skeletal involvement, craniosynostosis syndromes, dysostoses with predominant craniofacial involvement, dysostoses with predominant vertebral involvement, patellar dysostoses, brachydactylies, some disorders with limb hypoplasia-reduction defects, ectrodactyly with and without other manifestations, polydactyly-syndactyly-triphalangism group of disorders, and disorders with defects in joint formation and synostoses. Availability 4 weeks Gene Set Description
    [Show full text]
  • Anesthesia Management of Jansen's Metaphyseal Dysplasia
    CASE REPORT East J Med 21(1): 52-53, 2016 Anesthesia management of Jansen’s metaphyseal dysplasia Ugur Goktas1,*, Murat Tekin2, Ismail Kati3 1Department of Anesthesiology, Medical Faculty, Yuzuncu Yil University, Van, Turkey 2Department of Anesthesiology, Medical Faculty, Kocaeli University, Kocaeli, Turkey 3Department of Anesthesiology, Medical Faculty, Gazi University, Ankara, Turkey ABSTRACT Metaphyseal chondrodysplasia is a rare autosomal dominant disorder characterized by accumulation of cartilage in specifically metaphysis of tubular bones. Hyperkalemia and hypophosphatemia were seen most of these patients. In this article we intended to draw attention to some issues releated with anesthesia hereby that a 9 year-old patient with Jansen’s metaphyseal dysplasia. Key Words: general anesthesia, congenital anomalies, drugs Introduction (60%) were used for the anesthesia management. Operation duration was 50 min. LMA was removed Metaphyseal chondrodysplasia is a very rare postoperatively without any problem. Control serum autosomal dominant disorder affected of enchondral potassium and phosphor levels peroperatively and ossification in especially metaphysis (1). Firstly postoperatively were found normal (Table 1). After described in 1934 by Murk Jansen as various severity the recovery patient was sent to the ward without any and degrees (2), and metaphyseal chondrodysplasia problem. was classified in 1957 by Weil. Jansen type, which is the one of the most serious and rare. Hyperkalemia Discussion and hypophosphatemia were seen half of these Jansen type metaphyseal dysplasia is a very rare patients (3,4). In this article we intended to draw and serious disorder in the enchondral ossification attention to some issues related with anesthesia diseases. Affecting the metaphyses such as management that a 9 year-old patient a with Jansen’s achondroplasia, various types of rickets, metaphyseal dysplasia which to be a disorder very rare hypophosphatasia and multiple enchondromatosis and hardest diagnosing.
    [Show full text]
  • Discover Dysplasias Gene Panel
    Discover Dysplasias Gene Panel Discover Dysplasias tests 109 genes associated with skeletal dysplasias. This list is gathered from various sources, is not designed to be comprehensive, and is provided for reference only. This list is not medical advice and should not be used to make any diagnosis. Refer to lab reports in connection with potential diagnoses. Some genes below may also be associated with non-skeletal dysplasia disorders; those non-skeletal dysplasia disorders are not included on this list. Skeletal Disorders Tested Gene Condition(s) Inheritance ACP5 Spondyloenchondrodysplasia with immune dysregulation (SED) AR ADAMTS10 Weill-Marchesani syndrome (WMS) AR AGPS Rhizomelic chondrodysplasia punctata type 3 (RCDP) AR ALPL Hypophosphatasia AD/AR ANKH Craniometaphyseal dysplasia (CMD) AD Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy ARSB syndrome AR ARSE Chondrodysplasia punctata XLR Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) B3GALT6 Ehlers-Danlos syndrome progeroid type 2 (EDSP2) AR Multiple joint dislocations, short stature and craniofacial dysmorphism with B3GAT3 or without congenital heart defects (JDSCD) AR Spondyloepimetaphyseal dysplasia (SEMD) Thoracic aortic aneurysm and dissection (TADD), with or without additional BGN features, also known as Meester-Loeys syndrome XL Short stature, facial dysmorphism, and skeletal anomalies with or without BMP2 cardiac anomalies AD Acromesomelic dysplasia AR Brachydactyly type A2 AD BMPR1B Brachydactyly type A1 AD Desbuquois dysplasia CANT1 Multiple epiphyseal dysplasia (MED) AR CDC45 Meier-Gorlin syndrome AR This list is gathered from various sources, is not designed to be comprehensive, and is provided for reference only. This list is not medical advice and should not be used to make any diagnosis.
    [Show full text]
  • A Diagnostic Approach to Skeletal Dysplasias
    CHAPTER 16 A Diagnostic Approach to Skeletal Dysplasias SHEILA UNGER,ANDREA SUPERTI-FURGA,and DAVID L. RIMOIN [AU1] INTRODUCTION and outlines some of the more important radiographic ®ndings. The skeletal dysplasias are disorders characterized by developmental abnormalities of the skeleton. They form a large heterogeneous group and range in severity from BACKGROUND precocious osteoarthropathy to perinatal lethality [1,2]. Disproportionate short stature is the most frequent clin- Each skeletal dysplasia is rare, but collectively the ical complication but is not uniformly present. There are birth incidence is approximately 1/5000 [4,5]. The ori- more than 100 recognized forms of skeletal dysplasia, ginal classi®cation of skeletal dysplasias was quite sim- which can make determining a speci®c diagnosis dif®cult plistic. Patients were categorized as either short trunked [1]. This process is further complicated by the rarity of (Morquio syndrome) or short limbed (achondroplasia) the individual conditions. The establishment of a precise [6] (Fig. 1). As awareness of these conditions grew, their diagnosis is important for numerous reasons, including numbers expanded to more than 200 and this gave rise to prediction of adult height, accurate recurrence risk, pre- an unwieldy and complicated nomenclature [7]. In 1977, natal diagnosis in future pregnancies, and, most import- N. Butler made the prophetic statement that ``in recent ant, for proper clinical management. Once a skeletal years, attempts to classify bone dysplasias have been dysplasia is suspected, clinical and radiographic indica- more proli®c than enduring'' [8]. The advent of molecu- tors, along with more speci®c biochemical and molecular lar testing allowed the grouping of some dysplasias into tests, are employed to determine the underlying diagno- families.
    [Show full text]
  • Skeletal Dysplasias Precision Panel Overview Indications
    Skeletal Dysplasias Precision Panel Overview Skeletal Dysplasias, also known as osteochondrodysplasias, are a clinically and phenotypically heterogeneous group of more than 450 inherited disorders characterized by abnormalities mainly of cartilage and bone growth although they can also affect muscle, tendons and ligaments, resulting in abnormal shape and size of the skeleton and disproportion of long bones, spine and head. They differ in natural histories, prognoses, inheritance patterns and physiopathologic mechanisms. They range in severity from those that are embryonically lethal to those with minimum morbidity. Approximately 5% of children with congenital birth defects have skeletal dysplasias. Until recently, the diagnosis of skeletal dysplasia relied almost exclusively on careful phenotyping, however, the advent of genomic tests has the potential to make a more accurate and definite diagnosis based on the suspected clinical diagnosis. The 4 most common skeletal dysplasias are thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and achondrogenesis. The inheritance pattern of skeletal dysplasias is variable and includes autosomal dominant, recessive and X-linked. The Igenomix Skeletal Dysplasias Precision Panel can be used to make a directed and accurate differential diagnosis of skeletal abnormalities ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum
    [Show full text]
  • Whole Exome Sequencing Gene Package Skeletal Dysplasia, Version 2.1, 31-1-2020
    Whole Exome Sequencing Gene package Skeletal Dysplasia, Version 2.1, 31-1-2020 Technical information DNA was enriched using Agilent SureSelect DNA + SureSelect OneSeq 300kb CNV Backbone + Human All Exon V7 capture and paired-end sequenced on the Illumina platform (outsourced). The aim is to obtain 10 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate and non-unique reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA-MEM algorithm (reference: http://bio-bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ABCC9 Atrial fibrillation, familial, 12, 614050 601439 65 100 100 95 Cardiomyopathy, dilated, 1O, 608569 Hypertrichotic osteochondrodysplasia, 239850 ACAN Short stature and advanced bone age, with or without early-onset osteoarthritis
    [Show full text]
  • Subbarao K Skeletal Dysplasia (Sclerosing Dysplasias – Part I)
    REVIEW ARTICLE Skeletal Dysplasia (Sclerosing dysplasias – Part I) Subbarao K Padmasri Awardee Prof. Dr. Kakarla Subbarao, Hyderabad, India Introduction Dysplasia is a disturbance in the structure of Monitoring germ cell Mutations using bone and disturbance in growth intrinsic to skeletal dysplasias incidence of dysplasia is bone and / or cartilage. Several terms have 1500 for 9.5 million births (15 per 1,00,000) been used to describe Skeletal Dysplasia. Skeletal dysplasias constitute a complex SCLEROSING DYSPLASIAS group of bone and cartilage disorders. Three main groups have been reported. The first Osteopetrosis one is thought to be x-linked disorder Pyknodysostosis genetically inherited either as dominant or Osteopoikilosis recessive trait. The second group is Osteopathia striata spontaneous mutation. Third includes Dysosteosclerosis exposure to toxic or infective agent Worth’s sclerosteosis disrupting normal skeletal development. Van buchem’s dysplasia Camurati Engelman’s dysplasia The term skeletal dysplasia is sometimes Ribbing’s dysplasia used to include conditions which are not Pyle’s metaphyseal dysplasia actually skeletal dysplasia. According to Melorheosteosis revised classification of the constitutional Osteoectasia with hyperphosphatasia disorders of bone these conditions are Pachydermoperiosteosis (Touraine- divided into two broad groups: the Solente-Gole Syndrome) osteochondrodysplasias and the dysostoses. There are more than 450 well documented Evaluation by skeletal survey including long skeletal dysplasias. Many of the skeletal bones thoracic cage, hands, feet, cranium and dysplasias can be diagnosed in utero. This pelvis is adequate. Sclerosing dysplasias paper deals with post natal skeletal are described according to site of affliction dysplasias, particularly Sclerosing epiphyseal, metaphyseal, diaphyseal and dysplasias. generalized. Dysplasias with increased bone density Osteopetrosis (Marble Bones): Three forms are reported.
    [Show full text]
  • Pyle's Disease
    Journal of Medical Case Reports and Case Series ISSN: 2692-9880 Case report Volume 1 Issue 5 Pyle’s Disease: A Rare Case Report on 13 Year Female Child Dr. Venkatesh Gupta S.K¹, *, Animesh Yadav², Jayanth B² 1Department of Orthopedics JJMMC Davangere, Karnataka, India *Corresponding Author: Venkatesh Gupta S.K, Department of Orthopedics JJMMC Davangere, Karnataka, India Received date: 24 November 2020; Accepted date: 05 December 2020; Published date: 10 December 2020 Citation: Venkatesh Gupta S K, Yadav A, Jayanth B. Pyle’s Disease: A Rare Case Report on 13 Year Female Child. J Med Case Rep Case Series 1(5): https://doi.org/10.38207/jmcrcs20201058 Copyright: © 2020 Venkatesh Gupta S.K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Pyle metaphyseal dysplasia is an infrequent autosomal recessive skeletal disorder affecting the metaphysis of long tubular bones. A 13-year-old girl with Pyle’s disease presented with mild facial dysmorphism, deformity of the bilateral upper limb, cubitus valgus, and genu valgum. Her Skeletal radiology showed the distinctive Erlenmeyer flask sign at distal femoral and proximal tibia metaphyses along with an old pathological fracture of the left humerus with exuberant callus and minimal platyspondylosis. Keywords: pyle’s disease, metaphyseal dysplasia, erlenmeyer flask sign Introduction Metaphyseal Dysplasia also called Pyle’s disease is an autosomal of the elbow, dental malocclusion, and bone fragility [2]. Distinct recessive disorder that manifests at a variable age.
    [Show full text]
  • Achondroplasia: a Comprehensive Clinical Review Richard M
    Pauli Orphanet Journal of Rare Diseases (2019) 14:1 https://doi.org/10.1186/s13023-018-0972-6 REVIEW Open Access Achondroplasia: a comprehensive clinical review Richard M. Pauli Abstract Achondroplasia is the most common of the skeletal dysplasias that result in marked short stature (dwarfism). Although its clinical and radiologic phenotype has been described for more than 50 years, there is still a great deal to be learned about the medical issues that arise secondary to this diagnosis, the manner in which these are best diagnosed and addressed, and whether preventive strategies can ameliorate the problems that can compromise the health and well being of affected individuals. This review provides both an updated discussion of the care needs of those with achondroplasia and an exploration of the limits of evidence that is available regarding care recommendations, controversies that are currently present, and the many areas of ignorance that remain. Keywords: Achondroplasia, FGFR3, Skeletal dysplasia, Natural history, Care guidelines Introduction needed. Nonetheless, something has to be recom- Explicit guidelines for care of individuals with achon- mended for the care of affected individuals. Not sur- droplasia are available. Such guidelines were first devel- prisingly, lack of rigorous studies also results in oped by the American Academy of Pediatrics in 1995 considerable variation in the recommendations that are and revised in 2005 [1]. These are now again somewhat made. Unfortunately, this is not terribly different from out of date. Other care guidelines (for example see [2– much of current medical care. Some of these uncertain- 4]) and clinically oriented reviews (such as [5–7]) are ties will yield to studies of larger populations, as have also available.
    [Show full text]
  • Helpful Signs in the Imaging Diagnosis of Hereditary Musculoskeletal Disease
    Vanhoenacker, C, et al. Helpful Signs in the Imaging Diagnosis of Hereditary Musculoskeletal Disease. Journal of the Belgian Society of Radiology. 2017; 101(S2): 10, pp. 1–2. DOI: https://doi.org/10.5334/jbr-btr.1389 SHORT ABSTRACT Helpful Signs in the Imaging Diagnosis of Hereditary Musculoskeletal Disease Charlotte Vanhoenacker*, Geert Mortier† and Filip Vanhoenacker‡ Keywords: Hereditary Musculoskeletal Disorders; Dysplasia; Radiography Learning Objective To review and illustrate the different signs that may be useful in the imaging diagnosis of syndromes, dysplasia and other Hereditary Musculoskeletal Disorders. Background Identification of Hereditary Musculoskeletal Disorders is complicated because most diseases are rare and there are many diseases to memorize [1, 2]. In addition to clinical examination by a specialized pediatrician, radiography remains a very useful tool for initial identification of this group of disorders, as this examination will further guide the clinician for requesting specific and often expensive genetic tests. Because they are easy to remember and to teach, some signs are highly valuable in the correct radiological diag- Figure 1: Accordion sign in osteogenesis imperfecta type nosis of genetic bone disease. II in a 24-month-old fetus. Plain radiograph of the right lower leg showing marked shortening of the long bones Imaging Findings and accordion-like deformity. Signs can be divided into five main groups of which many examples will be shown during this lecture: 1. Radiodensity of the skeleton a. Marble bones and Rugger-Jersey sign in osteopetrosis b. Candle-wax dripping in melorheostosis c. Striation in osteopathia striata 2. Overall morphology of the skeleton a. S-sign, wedging in congenital spine deformities b.
    [Show full text]