Spondylo-epiphyseal dysplacea tarda (a case report).
A rare case of disproportionate short stature suggestive of spondylo-epiphyseal dysplasia tarda is reported and relevant literature reviewed. It is emphasized that its radiological features show a marked similarity to ochronotic spine, with which it is therefore commonly mistaken. An indeterminate pigment was observed in the liver biopsy in this case with connective tissue disorder.
Spondylo-cpiphyseal dysplasia (SED) tarda, is a condition which went by a number of designations including Morquio's disease before being correctly identified by Moroteaux and colleagues in 1957.
We report a case with disproportionate short stature suggestive of SED tards with an unusual liver pigment.
GDS, a 60-year-old Hindu male, tailor by profession was admitted to the King Edward Memorial Hospital complaining of difficulty in swallowing, slurred speech, unsteady gait and giddiness of sudden onset noticed immediately on rising in the morning. There was no history of headache, nausea or vomiting, visual disturbances or convulsions. There was no prior history of root pains in the neck or back radiating down the spine. There was no previous history of any form of illness in the past or hospitalisation.
On general examination he had a short stature of 55 inches with unequal extremities. (See [Figure - 1]). His span was 60.2 inches with an U/L segment ratio of 0.85. He had bony prominences at the elbow and shoulders. However, movements at these joints were painless and without any evidence of restriction of joint mobility or contractures. They were not hyper extensible either. His chest was barrel-shaped with a prominent sternum. The external genitalia and the secondary sexual characteristics were normal. There was no evidence of blackish pigmentation on the sclerae, pinnae or peripheral joints. On inquiry, he was single, born of non-consanguinous normal healthy parents of average stature. He had one brother and two sisters, all of whom died before their teens following some form of febrile illness, the details of which are not available.
His vital parameters were within normal limits. Oil examination of the central nervous system he was conscious, cooperative, moved all four limbs spontaneously and on command. His intelligence was average. Speech was slurred and there was evidence of lower cranial nerve involvement suggestive of a lateral medullary syndrome (Wallenberg's syndrome). On examination of the motor system the power in all the limbs was 4 + on the MRC scale, deep tendon reflexes were brisk bilaterally and both the planters were extensor. He also had bilateral cerebellar signs. All sensory modalities were impaired on the trunk and limbs, however on tile face they were normal. The rest of the systemic examination was unremarkable.
On investigations, his haemogram, urine and stool examination, blood chemistry were all within normal limits. His radiograph of the cervical spine showed moderately severe spondylosis. (See [Figure - 2]). Incidentally, routine radiograph of his chest revealed calcification of the intervertebral disc spaces throughout the spine characteristic of ochronotic spine. (See [Figure - 3] & [Figure - 4]). This prompted a detailed skeletal survey. (See [Figure - 5] & [Figure - 6]). Interestingly, on inquiry, he did not give any history of passing black coloured urine at any time in his life, nor did his urine blacken on standing, addition of an alkali like ferric chloride or after consuming a high tyrosine diet consisting of additional quantities of cheese in the ward under observation. His slit lamp examination of the eyes did not reveal any evidence of cortical clouding.
His liver function tests were within normal limits. His Serum. calcium, phosphorous and alkaline phosphatase, phosphatase were within normal limits. His liver biopsy revealed normal architecture with evidence of intracellular coarse brownish pigmentation (See [Figure:7]). Prussian blue reaction for iron, however, was negative. Other special staining reactions to reveal the nature of the pigment were also negative, viz. orcein for copper associated proteins and staining for bile pigment. The pigment was bleached by KMnO.4 Such non-specific reaction is given by melanin-like pigment or the pigment seen in Dubin-Johnson syndrome. However, there was no clinical or biochemical finding in favour of the same. Bromsulphalein (BSP) excretion test was normal. Urinary coproporphyrin studies were also normal with a normal ratio of coproporphyrins I : II. His chromosomal studies revealed a normal karyotype ruling out any form of chromosomal disorder.
Stature is a qualitative measure of height and a person is said to be short-stature if he or she falls below the third percentile of the normal growth charts, standardized for parental height and ethnic background,. In general as a rule, patients with disproportionate short stature have some form of skeletal dysplasias, whereas, those with relatively normal body proportions have some form of endocrine, nutritional, metabolic or other non-skeletal defects. Disproportionate dwarfism can either be due to an excessive shortening of the trunk in relation to the limbs, (short trunk dwarfism) or more commonly, the reverse (short limb dwarfism), characteristically seen in achondroplasia. Alternatively, the shortening may be predominantly proximal (rhizomelic), middle (mesomelic) or distal (acromelic) . In addition, the disease may be purely skeletal or may show extra skeletal rnanifestations . However, to make an accurate diagnosis, radiological survey o the complete skeleton is mandatory.
Radiologically, skeletal dysplasias are classified as either epiphyseal, metaphyseal (n diaphyseal with or without spinal involvement depending on the site and extent of the lesion seen,,. The radiographic survey of the complete skeleton in our patient revealed that he had a disease restricted to the spine and the proximal skeleton with predominant epiphyseal lesions, thereby entertaining the diagnosis of spondyloepiphyseal dysplasias of rhizomelic variety.
Spondyloephyseal dysplasias are a spectrum of disorders comprising of SED congenita, pseudoachondroplastic SED an SED tarda,. SED congenitas,, is a specific skeletal dysplasia inherited as autosomal dominant disorder which is evident at birth Cleft palate is common and over half of the have high grade myopia and/or retinal detach merit. The head is normal in size and because of a very short neck seems to rest directly on the shoulders. The chest is barrel shaped with, pectus carinatum. The limbs appear relatively long. Intelligence is normal. Radiologically, the main features are malformation of the spine and epiphysis of the tubular bones. The striking finding include retarded ossification of the pubic bones, knee epiphysis, calcanci and talii. The vertebral bodies are irregular and flat with narrow disc spaces.
Pseudoachondroplastic SED, is recognised in the first couple of years of life at which time the body proportion resembles those of achondroplasia. As the child starts to walk he is noticed to have a waddling gait, However, the distinction is very clear. There is no involvement of the growth plates, which are not associated with articular cartilages. Hence the skull, pelvis, ribs and pedicles of the vertebral bodies are not involved as they would have been in the case of achondroplasia. Radiologically, both the epiphysis appear more irregular in comparison with that seen in achondroplasia. The vertebrae are flat and show an anterior projection. In contrast, the skull is normal and the sacrosciatic notch is also normal.
SED tarda, is customarily used for the X-linked recessive disorder, however, autosomal dominant and recessive forms have been described. The dwarfism is apparent in the first decade and is primarily truncal. Pain in the back and hips with limitation of motion in these joints is frequent by the teens. Adult height varies from 52 to 62 inches. The radiological features are quite distinctive especially those of the spine. Characteristically, there is both humping up centrally and posteriorly and eburnation of the end-plates of the vertebral bodies. This at first glance suggests calcification of the intervertebral disc so much so that a casual similarity to ochronotic spine is often created. The epiphysis in the bones of the limbs are dysplastic, especially those in proximal parts of the limbs. Precocious arthritis develops in hips as well as in the spine.
The unusual features in our patient were his short stature with unequal body proportions. His radiographic survey demonstrated the characteristic features of SED tarda. Although the classic onset of SED tarda is in early childhood, adult cases have been reported on rare occasions,. The earliest report of a case with late presentation is by Nilsonne . However, of growing importance is the mild case,, which may escape detection in childhood and present as premature ostcoathritis, as in our patient.
It is also important to emphasize that in this disorder the characteristic changes in the end plates of the vertebral bodies often mimic the intervertebral disc space calcification seen in ochronotic spine. This radiological impression is created due to the humping and eburnation of the end plates, whereas in alkaptonuria, there is actual calcification of the intervertebral disc spaces. According to Zannoni et al, quinone of the homogentisic acid is mainly responsible for the ochronotic pigmentation seen in alkaptonuria and exposing an undeveloped photographic film immediately blackens it. Homogentisic acid can also be estimated by duanatography in urine and although unlikely to come positive in our patient it was not feasable for us to do it.
Iron, lipochrome, melanin-like pigment and bile are the common causes of liver pigmentation. However, even with special staining techniques the nature of the pigment could not be determined. His liver function tests including BSP excretion were absolutely normal. Nonetheless, the demonstration of liver pigment is important especially in view of the growing impression so aptly put by Carter CO that "Skeletal dysplasias are disorders of bones in search of an inborn error of metabolism". Early detection of these cases can result in better management with physiotherapy and supportive weight-bearing aids to minimize or delay the onset of degenerative arthritis with painful restriction of movements that these patients are so prone to develop.
We thank the Dean, Seth GS Medical College and King Edward Memorial Hospital, Parel, for permission to publish this case report.