Information on the following diseases can be found in the Related Disorders section of this report:

• Morquio Disease
• Spondyloepiphyseal Dysplasia Congenita
• Multiple Epiphyseal Dysplasia

Symptoms of spondyloepiphyseal dysplasia tarda are usually not apparent until six to eight years of age, hence the distinction “tarda” or “late”. This is the most obvious distinction from the congenital form, which is present and usually obvious at birth.

At about 6 to 8 or 10 years, spinal growth appears to decline and then stops. Limb growth continues, resulting in a disproportionately short trunk. Arm span may exceed height by 4 to 8 inches. The shoulder may assume a hunched appearance, the neck appears short and the chest broadens (barrel chest). During adolescence, various skeletal abnormalities may cause pain in the back, hips, shoulders, knees and ankles. As adults, people with spondyloepiphyseal dysplasia tarda may have mild dwarfism, with a short trunk, large chest cage and relatively normal limb length. Hands, head and feet appear to be normal size, but final adult height usually ranges from 4’10” to 5’6.”

Some individuals with spondyloepiphyseal dysplasia tarda may have unusual facial features such as a flat appearance to the face. The shape of the head is usually normal. Beginning in adolescence, progressive, degenerative, arthritis may affect many joints of the body, especially the hips.
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Spondyloepiphyseal dysplasia tarda is inherited as an X-linked recessive genetic trait. The gene responsible has been mapped to Gene Map Locus: Xp22.2-p22.1.

Chromosomes, which are present in the nucleus of all cells, carry the genetic information for each individual. Human cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome Xp22.2-p22.1" refers to a region between bands 22.1 and 22.2 on the short arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes, but one of the X chromosomes is normally "turned off" early in fetal development, and most of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder, but rarely display any of its manifestations.

Males have one X chromosome and, if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because fathers pass their Y chromosome to their male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
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Spondyloepiphyseal dysplasia tarda does not exhibit any ethnic predisposition. Affected individuals have been described in European, American, Asian, and Australian populations (but not in Africa-Americans to date). One estimate suggests that the incidence is 2 persons per million.
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Morquio disease, or Mucopolysaccharidosis IV is an autosomal recessively inherited metabolic disorder that is usually detectable by at 18 months of age. Its features include marked disproportionate short stature, clouding of the cornea, hearing loss, and enlarged liver. This disorder affects males and females equally. (For more information, choose "Morquio" as your search term in the Rare Disease Database.)

Spondyloepiphyseal dysplasia congenita is a disorder with autosomal dominant inheritance with considerable variability in the severity of symptoms. It is characterized by flat facial features, myopia, retinal detachment, cleft palate, clubfoot, short-trunk dwarfism, a waddling gait and normally sized hands and feet. This disorder, which is often detectable at birth, affects males and females equally. (For more information, choose "SED" as your search term in the Rare Disease Database.)

Multiple epiphyseal dysplasia, like SED Congenita, is dominantly inherited and affects males and females equally. The disorder is detectable between two and five years of age with the appearance of a waddling gait and variable short stature. Patients may experience pain as a result of osteoarthritic changes in the joints. Mutations in one of four possible genes are responsible for MED. .

Diagnosis
The diagnosis of SEDT is usually made on the basis of characteristic radiological (X-ray) findings. These appear in late childhood but usually before puberty.

Some of these signs are: flattened vertebral bodies (platyspondyly), typical distortions of the upper and lower vertebral surfaces (“humping”), short necks of the thigh bones (femurs), a deformity where the femur meets the hip (coxa vara), and signs of early arthritis, especially in the hip joints.

Treatment
Treatment is supportive and symptomatic. Hip replacement may be necessary by the fourth to fifth decade of life.
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McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Spondyloepiphyseal Dysplasia Tarda, X-Linked. Entry Number; 313400: Last Edit Date; 3/2/2000.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Spondyloepiphyseal Dysplasia Tarda, Toledo Type. Entry Number; 271630: Last Edit Date; 5/11/1999.

TEXTBOOKS
Hicks J. Spondyloepiphyseal Dysplasia Tarda. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:729-30.

Jones KL. Ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:378-79.

Buyce ML. Editor-in-Chief. Birth Defects Encyclopedia. Blackwell Scientific Publications. Center for Birth Defects Information Services, Inc., Dover, MA; 1990:1588-89.

JOURNAL ARTICLES
Gedeon AK, Tiller GE, Le Merrer M, et al. The molecular basis of X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet. 2001;68:1386-97.

Tiller GE, Hannig VL, Dozier D, et al. A recurrent RNA-splicing mutation in the SEDL gene causes X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet.2001;68:1398-407.

Whyte MP, Gottesman GS, Eddy MC, McAlister WH. X-linked recessive spondyloepiphyseal dysplasia tarda: clinical and radiographic evolution in a 6-generation kindred and review of the literature. Medicine.1999;78:9-25.

Gedeon AK, Colley A, Jamieson R, et al. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nat Genet. 1999;22:400-04.

FROM THE INTERNET
Tiller GE, Hannig VL. X-Linked Spondyloepiphyseal Dysplasia Tarda. GENEReviews. Posted: 1 November 2001. 8pp.
www.geneclinics.org/servlet/access?id=8888890&key=0fTYI8pkjDwBj&gry

Gedeon A. Spondyloepiphyseal dysplasia tarda. Hum-Molgen News Alert. Posted: 10/21/1999. 1p.
www.hum-molgen.de/bb/Forum2/HTML/000004.html

Gpnotebook. spondyloepiphyseal dysplasias. nd. 1p.
www.gpnotebook.co.uk/cache/-2053505010.htm

POSNA (Pediatric Orthopedic Society of North America.) Spondylo-epiphyseal dysplasia (SED). nd. 2pp.
www.posna.org/CoreCurriculum/Book3/Spondyloepiphyseal%20dysplasia%20(SED).pdf