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Spondyloepiphyseal Dysplasia

  • Author: Shital Parikh, MD; Chief Editor: Dennis P Grogan, MD  more...
 
Updated: Nov 02, 2015
 

Background

Spondyloepiphyseal dysplasia (SED) is a descriptive term for a group of disorders with primary involvement of the vertebrae and epiphyseal centers resulting in a short-trunk disproportionate dwarfism. Spondylo refers to spine, epiphyseal refers to the growing ends of bones, and dysplasia refers to abnormal growth.

Two major types of SED are recognized, namely, SED congenita and SED tarda. Spranger and Wiedemann first described SED congenita in 1966,[1] and Spranger and Langer provided a further review of 29 patients in 1970.[2] In 1969, Fraser noted the particular association of SED with myopia, retinal detachment, and deafness.[3] In 1939, Jacobsen recognized SED tarda in a report of 20 patients.[4]

An image depicting spondyloepiphyseal dysplasia can be seen below.

Spondyloepiphyseal dysplasia. Radiograph of the pe Spondyloepiphyseal dysplasia. Radiograph of the pelvis depicting delayed ossification of capital femoral epiphyses, metaphyseal flaring, horizontal acetabular roofs, triangular fragment on the inferior aspect of the broad femoral neck, and coxa vara.
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Pathophysiology

Dwarfing conditions are frequently referred to as short-limb or short-trunk types, according to whether the limbs or trunk is more extensively involved. SED, metatropic dysplasia, and Kniest syndrome are considered short-trunk dwarfing conditions. SED is a generalized dysplasia with primary involvement of the vertebrae and proximal epiphyseal centers. Other generalized dysplasias with significant vertebral involvement, such as spondylometaphyseal dysplasia or spondyloepimetaphyseal dysplasia, affect the metaphyseal region of the long bone or metaphyseal and epiphyseal region of the long bone, respectively.[5]

The clinical and radiographic differences among the various spondylodysplasias are frequently age related. SED congenita is a nonlethal form of congenital dwarfism characterized by typical skeletal dysplasias, vertebral changes, and ocular manifestations. It can be diagnosed at birth. In contrast, SED tarda is milder than SED congenita and late in onset, and appearance may be normal at birth.

With the increasing molecular definition of several types of collagen and recognition of the concentration of certain types in cartilage tissue, many skeletal dysplasias have now been defined as collagen abnormalities. Studies have indicated abnormal synthesis of type II collagen in SED congenita. Type II collagen is a primary matrix protein of physeal and epiphyseal cartilage. Because an abnormality in type II collagen should affect the molecules throughout the body, how the currently defined abnormality can translate into major structural abnormalities of the vertebrae and capital femoral epiphysis while leaving the distal femur, proximal tibia, and other regions structurally unaffected remains unclear.

Other rare forms of SED have been described. SED Maroteaux type is a form of SED with manifestations limited to the musculoskeletal system.[6] SED tarda Toledo type (first described in 1978) is a form of SED tarda with peripheral corneal opacities and a qualitative abnormality of urinary mucopolysaccharides, mainly chondroitin-6-sulfate. In 1982, Wynne-Davies recognized a form of SED tarda associated with progressive arthropathy similar to juvenile rheumatoid arthritis.[7] Kohn recognized an autosomal recessive variant of SED tarda associated with mental retardation.[8]

Similarly, other forms of SED, such as SED with brachydactyly and SED tarda Namaqualand type (NSED), have been recognized and classified under the International Nomenclature and Classification of the Osteochondrodysplasias. Bailey suggested 2 groups in addition to SED congenita and SED tarda; these are pseudo-Morquio disease and pseudoachondroplasia SED.[9] Only the common types of SED (ie, SED congenita and SED tarda) are discussed in detail in this article.[10]

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Epidemiology

Frequency

International

SED congenita is a rare genetic disorder. The prevalence is approximately 3.4 per million population.[7] The incidence rate is approximately 1 per 100,000 live births.

Mortality/Morbidity

The standardized mortality ratio is not increased for patients with SED.

Morbidity associated with SED may include the following conditions:

Race

Most of the studies on SED involve patients from North America, Europe, and South Africa. Isolated cases have been reported from Asia and other Arab countries. Though patterns of inheritance have been identified, most cases result from sporadic mutation. No racial predilection exists.

Sex

SED congenita is autosomal dominant; hence, males and females are affected in equal numbers. Occasional cases of autosomal recessive forms have been identified.

SED tarda is X-linked recessive; hence, only males are affected. However, certain autosomal forms have been recognized, so females are occasionally affected.

Age

SED congenita can be diagnosed at birth.

In SED tarda, appearance may be normal at birth, but the condition becomes apparent later in life. Typically, the condition is clinically manifested around puberty. However, radiographic abnormalities may appear earlier.

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Contributor Information and Disclosures
Author

Shital Parikh, MD Associate Professor, Department of Pediatric Orthopedic Surgery, Cincinnati Children's Hospital Medical Center

Shital Parikh, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Medical Association, Orthopaedic Research Society

Disclosure: Nothing to disclose.

Coauthor(s)

Preeti Batra, MD, MBBS Staff Physician, Department of Radiology, VS Hospital, India

Disclosure: Nothing to disclose.

Alvin H Crawford, MD, FACS Professor Emeritus of Pediatrics and Orthopedic Surgery, University of Cincinnati College of Medicine; Director, Founding Division of Pediatric Orthopedic Surgery, Department of Orthopedic Surgery, Cincinnati Children's Hospital Medical Center

Alvin H Crawford, MD, FACS is a member of the following medical societies: Ohio State Medical Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

George H Thompson, MD Director of Pediatric Orthopedic Surgery, Rainbow Babies and Children’s Hospital, University Hospitals Case Medical Center, and MetroHealth Medical Center; Professor of Orthopedic Surgery and Pediatrics, Case Western Reserve University School of Medicine

George H Thompson, MD is a member of the following medical societies: American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Academy of Orthopaedic Surgeons

Disclosure: Received none from OrthoPediatrics for consulting; Received salary from Journal of Pediatric Orthopaedics for management position; Received none from SpineForm for consulting; Received none from SICOT for board membership.

Chief Editor

Dennis P Grogan, MD Clinical Professor (Retired), Department of Orthopedic Surgery, University of South Florida College of Medicine; Orthopedic Surgeon, Department of Orthopedic Surgery, Shriners Hospital for Children of Tampa

Dennis P Grogan, MD is a member of the following medical societies: American Medical Association, American Orthopaedic Association, Scoliosis Research Society, Irish American Orthopaedic Society, Pediatric Orthopaedic Society of North America, American Academy of Orthopaedic Surgeons, American Orthopaedic Foot and Ankle Society, Eastern Orthopaedic Association

Disclosure: Nothing to disclose.

Additional Contributors

Charles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children's Hospital Medical Center

Charles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association

Disclosure: Nothing to disclose.

References
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Spondyloepiphyseal dysplasia. Radiograph of the pelvis depicting delayed ossification of capital femoral epiphyses, metaphyseal flaring, horizontal acetabular roofs, triangular fragment on the inferior aspect of the broad femoral neck, and coxa vara.
Spondyloepiphyseal dysplasia. Radiograph of the spine depicting increased anteroposterior diameter, platyspondyly, posterior wedging of the vertebrae, and increased lumbar lordosis.
Spondyloepiphyseal dysplasia. Radiograph of the upper cervical vertebrae depicting ununited odontoid process.
Spondyloepiphyseal dysplasia. Radiograph of the chest, depicting bell-shaped chest and decreased height of the trunk due to platyspondyly.
Spondyloepiphyseal dysplasia. Radiograph of shoulder, depicting severe epiphyseal involvement of proximal humerus, leading to premature osteoarthritis.
Clinical picture of a child with spondyloepiphyseal dysplasia. The child had a limp when she walked. The radiographs reveal Perthes-like changes. Both the hips appear to be in a similar stage of progression.
Clinical picture of a girl with spondyloepiphyseal dysplasia. The sitting height is significantly affected. The trunk is disproportionately shorter than the extremities. The radiographs reveal platyspondyly.
Table 1. Differential Diagnoses of Spondyloepiphyseal Dysplasia Congenita Versus Morquio Disease
Characteristic SED Congenita Morquio Disease
Inheritance Autosomal dominant Autosomal recessive
Molecule affected Collagen type II Mucopolysaccharides
Clinical manifestation Birth End of first year
Flared ilia Absent Present
Os pubis ossification Absent Present
Acetabular angle Small Wide
Femoral neck Varus Valgus
Hands and feet affected Minimal Severe
Eye changes Myopia, retinal tears Corneal clouding
Keratosulfaturia Absent Present
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