R. Wynne-Davies, MB., Ph.D., F.R.C.S., Department of Orthopaedic Surgery (Clinical Genetics), University of Edinburgh, 24 Buccleuch Place, Edinburgh EH8 9LN, Scotland. J. H. S. Scott, F.R.C.S.Ed., Consultant Orthopaedic Surgeon, Princess Margaret Rose Orthopaedic Hospital, Fairmilehead, Edinburgh EHIO 7ED, Scotland. Request for reprints should be sent to Miss R. Wynne-Davies. VOL. 61-B, No. 3, AUGUST 1979 301 INHERITANCE AND SPONDYLOLISTHESIS A RADIOGRAPHIC FAMILY SURVEY RUTH WYNNE-DAVIES, J. H. S. SCOTF From the Department of Orthopaedic Surgery (Clinical Genetics), University of Edinburgh A radiographic survey has been carried out of 147 first-degree relatives offorty-seven patients treated in Edinburgh for spondylolisthesis of the fifth lumbar vertebra; twelve patients had the dysplastic (congenital) type and thirty-five an isthmic defect. The survey identified 19 per cent of relatives with spondylolysis, and index patients with each type of spondylolisthesis had relatives with the opposite type. Index patients with the dysplastic form had a higher proportion ofaffected relatives (33 per cent) than had those with the isthmic type (15 per cent), but both figures were significantly in excess of the estimated frequency for the general population of under 1 per cent and 5 per cent respectively. Spina bifida occulta at the fifth lumbar or first sacral level or both, and lumbosacral s(gmental defects were commoner amongst all individuals with spondylolysis than amongst unaffected relatives (dysplastic form 94 per cent, isthmic type 32 per cent, unaffected relatives 7 per cent). However, there was no single instance ofa neural tube defect (anencephaly, spina bifida with or without meningocele, other generalised vertebral anomalies or spinal dysraphism) amongst 826 first-, second- or third-degree relatives. It is concluded that the developmental defects of the vertebrae associated with spondylolysis are not aetiologically related to the neural tube defects. The one in three risk of spondylolysis to near relatives of patients with the dysplastic form ofspondylolisthesis is emphasised in order that the deformity in their sibs and children can be recognised at any early age. Over the past forty years there have been numerous reports of families with spondylolysis and spondylolis- thesis (Friberg 1939; Wiltse 1957; Laurent 1958; King 1966; Amuso and Mankin 1967; Turner and Bianco 1 97 1 ; Haukipuro et al. 1 978). More significantly, there have been some prospective family surveys with radiographic examination of unselected members (Baker and McHollick 1956; Wiltse 1960, 1962; Wiltse and Hutchinson 1965; Yano 1967) and the results have been remarkably consistent with a frequency of the same disorder in near relatives of about 27 per cent, a considerable increase over the estimated frequency of 4 to 8 per cent of most general populations studied (Roche and Rowe 1952; Barr 1955; Baker and McHollick 1956; Nathan 1959; Yano 1967; Krenz and Troup 1973). An exception to this was established by Stewart (1 953), who found an unusually high frequency amongst Alaskan Eskimos. He, Rowe and Roche (1953) and Kettelkamp and Wright (1971) all noted that there was no defect at the outset of postnatal life, though some 5 per cent of children were affected by the age of six years and over 20 per cent by the age of thirty-five. The high frequency in this race was thought possibly to be due to unusual mechanical stresses and fatigue fractures of the pars interarticularis. Many writers have noted a high proportion of spina bifida occulta at the fifth lumbar or first sacral level among patients with spondylolysis (Friberg 1939; Roche and Rowe 1952; Wiltse 1962). Blackburne and Velikas (1977) found that the risk of a progressive vertebral slip was greater in patients with a midline lumbosacral defect than in those without such a defect. An additional or missing lumbar vertebra or transitional vertebrae at the lumbosacral level has also been noted as being more frequent in spondylolytic patients than in the general population (Friberg 1939; Roche and Rowe 1952). Newman (1955, 1963) described five types of spondylolisthesis, including a congenital Type I associ- ated with sacral spina bifida and deficient development of the superior sacral facet, and Type Ii “spondylolytic spondylolisthesis” with an elongation or break in the pars interarticularis. Wiltse, Newman and Macnab ( 1976) have more recently reclassified these two groups as the dysplastic and isthmic forms of spondylolisthesis (Figs. 1 to 4). The aim of the current survey was to take an unselected group of patients, all of whom had presented with dysplastic or isthmic spondylolisthesis of the fifth lumbar vertebra, and to carry out a radiographic review
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
R. Wynne-Davies, MB., Ph.D., F.R.C.S., Department of Orthopaedic Surgery (Clinical Genetics), University of Edinburgh, 24 Buccleuch Place, Edinburgh EH8 9LN, Scotland. J. H. S. Scott, F.R.C.S.Ed., Consultant Orthopaedic Surgeon, Princess Margaret Rose Orthopaedic Hospital, Fairmilehead, Edinburgh EHIO 7ED, Scotland.
Request for reprints should be sent to Miss R. Wynne-Davies.
VOL. 61-B, No. 3, AUGUST 1979 301
INHERITANCE AND SPONDYLOLISTHESIS
From the Department of Orthopaedic Surgery (Clinical Genetics), University of Edinburgh
A radiographic survey has been carried out of 147 first-degree relatives offorty-seven patients treated
in Edinburgh for spondylolisthesis of the fifth lumbar vertebra; twelve patients had the dysplastic
(congenital) type and thirty-five an isthmic defect. The survey identified 19 per cent of relatives with
spondylolysis, and index patients with each type of spondylolisthesis had relatives with the opposite type.
Index patients with the dysplastic form had a higher proportion ofaffected relatives (33 per cent) than had
those with the isthmic type (15 per cent), but both figures were significantly in excess of the estimated
frequency for the general population of under 1 per cent and 5 per cent respectively.
Spina bifida occulta at the fifth lumbar or first sacral level or both, and lumbosacral s(gmental defects
were commoner amongst all individuals with spondylolysis than amongst unaffected relatives (dysplastic
form 94 per cent, isthmic type 32 per cent, unaffected relatives 7 per cent). However, there was no single
instance ofa neural tube defect (anencephaly, spina bifida with or without meningocele, other generalised vertebral anomalies or spinal dysraphism) amongst 826 first-, second- or third-degree relatives. It is
concluded that the developmental defects of the vertebrae associated with spondylolysis are not
aetiologically related to the neural tube defects. The one in three risk of spondylolysis to near relatives of
patients with the dysplastic form ofspondylolisthesis is emphasised in order that the deformity in their sibs
and children can be recognised at any early age.
Over the past forty years there have been numerous
reports of families with spondylolysis and spondylolis-
thesis (Friberg 1939; Wiltse 1957; Laurent 1958; King
1966; Amuso and Mankin 1967; Turner and Bianco
1 97 1 ; Haukipuro et al. 1 978). More significantly, there
have been some prospective family surveys with
radiographic examination of unselected members
(Baker and McHollick 1956; Wiltse 1960, 1962; Wiltse
and Hutchinson 1965; Yano 1967) and the results have
been remarkably consistent with a frequency of the same
disorder in near relatives of about 27 per cent, a
considerable increase over the estimated frequency of 4
to 8 per cent of most general populations studied (Roche
and Rowe 1952; Barr 1955; Baker and McHollick
1956; Nathan 1959; Yano 1967; Krenz and Troup
1973). An exception to this was established by Stewart
(1 953), who found an unusually high frequency amongst
Alaskan Eskimos. He, Rowe and Roche (1953) and
Kettelkamp and Wright (1971) all noted that there was
no defect at the outset of postnatal life, though some 5
per cent of children were affected by the age of six years
and over 20 per cent by the age of thirty-five. The high
frequency in this race was thought possibly to be due to
unusual mechanical stresses and fatigue fractures of the
pars interarticularis.
bifida occulta at the fifth lumbar or first sacral level
among patients with spondylolysis (Friberg 1939;
Roche and Rowe 1952; Wiltse 1962). Blackburne and
Velikas (1977) found that the risk of a progressive
vertebral slip was greater in patients with a midline
lumbosacral defect than in those without such a defect.
An additional or missing lumbar vertebra or transitional
vertebrae at the lumbosacral level has also been noted as
being more frequent in spondylolytic patients than in the
general population (Friberg 1939; Roche and Rowe
1952).
ated with sacral spina bifida and deficient development
of the superior sacral facet, and Type Ii “spondylolytic
spondylolisthesis” with an elongation or break in the
pars interarticularis. Wiltse, Newman and Macnab
( 1976) have more recently reclassified these two groups
as the dysplastic and isthmic forms of spondylolisthesis
(Figs. 1 to 4).
The aim of the current survey was to take an
unselected group of patients, all of whom had presented
with dysplastic or isthmic spondylolisthesis of the fifth
lumbar vertebra, and to carry out a radiographic review
302 RUTH wYNNE-DAvIE5. J H. 5 SCOTt
THE JOURNAL OF BONE AND JOINT SURGERY
Fig. I Fig. 2
Figure 1-In the common isthmic form of spondylolisthesis the anteroposterior view is normal. Figure 2-The lateral view shows the elongation or break in the pars interarticularis. The line of the superior sacral facet joint approaches the vertical.
of their first-degree relatives (parents, sibs and chil-
dren) looking for a similar defect. It was hoped to
identify the mode of inheritance, distinguishing between
the dysplastic and isthmic types and, in view of the
known association with spina bifida occulta and
vertebral anomalies at the lumbosacral level, to establish
whether spondylolisthesis was aetiologically related to
the neural tube defects of anencephaly, spina bifida with
or without meningocele, multiple segmental anomalies
of the vertebrae and spinal dysraphism.
MATERIAL AND METHOD
A survey was made of forty-seven patients with spondylolisthesis, all living within the Edinburgh area and attending one orthopaedic clinic
(JHSS) Their ages ranged from five to sixty-six years with a mean of
thirty-two years. Twelve had the dysplastic (congenital) type of
spondylolisthesis and thirty-five the isthmic type Patients with
generalised skeletal disease, degenerative spondylolisthesis or that
clearly due to acute injury were excluded
For the genetic survey, the patients were tnitially visited in their
homes and the pedigree obtained. A history of developmental defects
was taken and, where necessary, confirmed from medical records.
Epidemiological information was collected in relation to social and
birth histories, parental age and parity Subsequently all first-degree
relatives willing to help with the survey attended hospital for further
examination and radiography The forty-seven index patients had a
total of 300 first-degree relatives, but only 1 95 were still alive, over
five years of age and available in the district. Of these, 147 (75.4 per
cent) attended for radiography Anteroposterior and lateral views of
the lumbar spine were taken routinely and oblique views in addition
when the diagnosis could not be made on the first two radiographs.
RESULTS
Sex ratio. In the dysplastic group there were seven males
and five females (sex ratio 1 .4), and in the isthmic group
twenty-five males and ten females (sex ratio 2.5), these
ratios being similar to findings in other surveys.
Affected relatives. Only six o the 147 relatives (4 per
VOL. 61-B, No. 3, AUGUST 1979
INHERITANCE AND SPONDYLOLISTHESIS
Figure 3-In the less common dysplastic form of spondylolisthesis the anteroposterior view frequently shows spina bifida
occulta or transitional lumbosacral vertebrae or both. Figure 4-In this lateral view there is a break in the pars interarticularis, but this need not be present. The most important difference between this and the isthmic type is the line of the superior sacral
facet joint, which here approaches the horizontal.
303
spondylolysis; but on radiography twenty-eight of them
were shown to be affected (19 per cent, or nearly five
times as many as suspected on the history alone). This 19
per cent included 22 per cent of parents, 14 per cent of
sibs and 24 per cent of children of the adult index
Table I. Proportions of first-degree relatives with spondylolysis or spondylolisthesis
Patients Parents Sibs Children Total
(12) Dysplastic type 6 of 18 2 of 12 3 of 3 11 of 33 (33.0%)
(35) Isthmic type 5 of 32 7 of 51 5 of 31 17 of 114 (14.9%)
(47) Total I 1 of 50 (22.0%)
9 of 63 (14.3%)
8 of 34 (23.5%)
28 of 147 (19.0%)
seventy years; six were under the age of twenty, eleven
were between the ages of twenty and thirty-nine, and
eleven were forty years and over. There was a higher
proportion of affected relatives of patients with the
dysplastic type compared with the isthmic group (33 and
1 5 per cent respectively). Both these figures are
significantly in excess of the expected frequency for the
general population of approximately 5 per cent (esti-
mated at under 1 per cent for the dysplastic form and 4 to
5 per cent for the isthmic form). Each group of index
patients, dysplastic and isthmic, had relatives with the
opposite type of defect, the dysplastic form always being
less common. Of the eleven affected relatives of the
dysplastic group of patients, ten had an isthmic and only
one a dysplastic defect. In the isthmic group, fourteen of
the seventeen affected relatives had an isthmic lesion
and only three a dysplastic defect (Fig. 5).
FIRST-DEGREE RELATIVES
#{149}/,/,‘Z//ZZZZZA
There was one instance of consanguinity among the
isthmic group, the patient’s parents being first cousins,
but neither they nor a brother had a lesion. There was
one pair of (dizygous) twins in the survey, only one
affected with the isthmic lesion.
Back symptoms in relatives. Only six of the twenty-eight
relatives (2 1 per cent) with a proven spondylolytic lesion
had any symptoms; this was little above the figure of 16
per cent of the remaining relatives who complained of
backache but did not have a defect (twenty of 1 19
individuals). Nevertheless, backache could be ofvalue in
diagnosing spondylolysis under the age of twenty years
since all these younger relatives did have a lesion.
(for the Edinburgh region) would be eleven, or 8 per
cent of the total of 143 sibs (Wynne-Davies 1975).
Epidemiological data. There were no abnormal findings
relating to the pregnancy or birth of these patients,
where these histories were available. Length of gesta-
tion, presentation, birth weight, season of birth, social
class, previous abortions or stillbirths were all within the
expected range. The only finding of probable signifi-
cance was a raised maternal age in patients with the
isthmic type of lesion (28.39± 1 .03 years) compared
with control figures of 26.04±0.22 years
(0.05 >P>-0.025).
Diagrammatic illustration of the proportions of patients and their affected relatives with the dysplastic and isthmic forms of spondylolis-
thesis or spondylolysis.
Eleven of the twelve patients with a dysplastic lesion had
either spina bifida occulta or segmental defects in the
lumbosacral area or both; all four relatives with a
dysplastic lesion had an associated defect here. Of the
patients with an isthmic lesion, eleven of the thirty-five
had such a defect, as had eight of their twenty-four
affected relatives. In contrast, only eight of 119 (6.7 per
cent) unaffected relatives had a defect (Table II). Spina
bifida occulta at the fifth lumbar or first sacral level is
common in the general population, occurring in 25 per
cent or more; other lumbosacral defects occur less
frequently, probably in only 5 to 8 per cent of the
population (Paterson 1893; le Double 1912; Friberg
1939; Friedman, Fischer and Van Demark 1946).
Clearly these additional developmental defects are
particularly associated with spondylolysis and spon-
dylolisthesis, being almost invariable in the dysplastic
type and present in one third of individuals with an
isthmic lesion.
patients or their relatives, and in particular there was no
single instance of a neural tube defect among 826 first-,
second- or third-degree relatives. An accurate compari-
son can be made with the sibs of spondylolisthetic
patients. If these two lesions were aetiologically related,
the expected number of sibs with a neural tube defect
It is clear that a lumbosacral midline lesion or other
segmental defect at this level is common amongst
individuals with spondylolysis and spondylolisthesis, but
since this is not associated with an increased family
frequency of the neural tube defects we conclude that
the two disorders are not aetiologically related.
It seems likely that there is a genetic element to
both the dysplastic and isthmic types of spondylolis-
thesis. Since each defect appears in the other’s family in
a higher proportion than expected for the generil
population, they are likely to be aetiologically related,
but the dysplastic type presents a higher risk to near
relatives (one in three affected) than the isthmic form
(only one in seven affected). This high risk needs
emphasising in order that affected sibs and children of
these patients can be identified at an early age. The
lower proportion of affected relatives among patients
with an isthmic lesion could be due to the fact that it is
not possible to isolate all those patients who have a
simple traumatic (though not acute) lesion from those
Table IL Proportions of index patients and relatives with lumbosacral midline or other segmental defects
Spina bifida occulta (L5 or Si)
Lumbosacral segmental defect
cannot be certainly identified on such a small survey as
this but it probably lies between autosomal dominant
inheritance with reduced penetrance and multifactorial
inheritance. Our view is that there is likely to be a
genetic predisposition to spondylolisthesis; if an associ-
ated lumbosacral spina bifida occulta or segmental
defect is present, it raises the probability of a vertebral
slip which may then be precipitated by quite minor
injury.
REFERENCES
Amuso, S. J., and Mankin, H. J. (1967) Hereditary spondylolisthesis and spina bifida. Journal ofBone and Joint Surgery. 49-A, 507-513.
Baker, D. R., and McHollIck, W. (1 956) Spondyloschisis and spondylolisthesis in children.JournalofBone andJoint Surgery. 38-A, 933-934.
Barr, J. S. (1955) Spondylolisthesis. Journal of Bone and Joint Surgery, 37-A, 878-880.
Blackburne, J. S., and Velikas, E. P. (1977) Spondylolisthesis in children and adults. Proceedings ofthe RovalSocietv a/Medicine. 70, 42 1-422.
Friberg, S. (1939) Studies on spondylolisthesis. Acta Chirurgica Scandinas’ica, Supplement 55.
Friedman, M. M., Fischer, F. J., and Van Demark, R. E. (1946) Lumbosacral roentgenograms of one hundred soldiers. America,z Journal of
Roentgenology and Radium Therapy, 55, 292-298.
Haukipuro, K., Ker#{225}nen,N., Kolvisto, E., Llndholm, R., Norio, R., and Punto, L. ( 1 978) Familial occurrence of lumbar spondylolysis and
spondylolisthesis. Clinical Genetics, 13, 471-476. Kettelkamp, D. B., and Wright, D. C. (1971) Spondylolysis in the Alaskan Eskimo. Journal of Bone and Joint Surgers. 53-A, 563-566.
King, A. B. (1966) Experiences with spondylolisthesis. Bulletin ofthe Johns Hopkins Hospital, 118, 2-9. Krenz, J., and Troup, J. D. G. (1 973) The structure of the pars interarticularis of the lower lumbar vertebrae and its relation to the etiology of
spondylolysis. Journal of Bone and Joint Surgery, 55-B, 735-741.
Laurent, L. E. (1958) Spondylolisthesis. Acta Orthopaedica Scandinavica, Supplement 35.
Ic Double, A. I. ( 1 9 1 2) Trait#{233}des Variations de la Colonne vert#{233}brale cle l’Ho,nme. Paris: Vigot Fr#{232}res.
Nathan, H. (1959) Spondylolysis. Journal of Bone and Joint Surgery, 41-A, 303-320.
Newman, P. H. (1955) Spondylolisthesis, its cause and effect. Annals ofthe Royal College ofSurgeons ofEngland, 16, 305-323.
Newman, P. H. (1963) The etiology of spondylolisthesis. Journal of Bone and Joint Surgery, 45-B, 39-59.
Paterson, A. M. (1893) The human sacrum. Scientific Transactions ofthe Royal Dublin Society, N.S. 5, 123-204.
Roche, M. B., and Rowe, G. G. ( 1 952) The incidence of separate neural arch and coincident bone variations. Journal ofBone and Joint Surgery. 34-A, 491-494.
Rowe, G. G., and Roche, M. B. ( 1 953) The etiology of separate neural arch. Journal of Bone and Joint Surgery. 35-A, 1 02- 1 10.
Stewart, T. D. ( I 953) The age incidence of neural-arch defects in Alaskan natives, considered from the standpoint of etiology. Journal of Bone and Joint Surgery, 35-A, 937-950.
Turner, R. H., and Bianco, A. J., Jun. ( 1 97 1 ) Spondylolysis and spondylolisthesis in children and teen-agers. Journal ofBone andJoint Surgery.
53-A, 1298-1306.
Wiltse, L. L. (1957) Etiology of spondylolisthesis. Clinical Orthopaedics. 10, 48-60.
Wiltse, L. L. (1 960) Spondylolisthesis. Etiology and comparative efficacy of various surgical procedures. Journal of Bone and Joint Surgery. 42-A, 1441.
Wiltse, L. L. (1962) The etiology of spondylolisthesis. Journal of Bone and Joint Surgery, 44-A, 539-560.
Wiltse, L. L., and Hutchinson, R. H. (1965) Spondylolisthesis: etiology and treatment. Journal of Bone and Joint Surgery. 47-A, 1096. Wiltse, L. L., Newman, P. H., and Macnab, I. (1976) Classification of spondylolysis and spondylolisthesis. Clinical Orthopaedics and Related
Research, 117, 23-29. Wiltse, L. L., Widell, E. H., Jun., and Jackson, D. W. ( 1 975) Fatigue fracture: the basic lesion in isthmic spondylolisthesis. Journal ofBone and
Joint Surgery, 57-A, 17-22.
Wynne.Davles, R. ( 1 975) Congenital vertebral anomalies: aetiology and relationship to spina bifida cystica. Journal of Medical Genetics, 12, 280-288.
Yano, T. (1967) Familial incidence of spondylolysis. Journal of Bone and Joint Surgery, 49-B, 390.
VOL. 61-B, No. 3, AUGUST 1979
Request for reprints should be sent to Miss R. Wynne-Davies.
VOL. 61-B, No. 3, AUGUST 1979 301
INHERITANCE AND SPONDYLOLISTHESIS
From the Department of Orthopaedic Surgery (Clinical Genetics), University of Edinburgh
A radiographic survey has been carried out of 147 first-degree relatives offorty-seven patients treated
in Edinburgh for spondylolisthesis of the fifth lumbar vertebra; twelve patients had the dysplastic
(congenital) type and thirty-five an isthmic defect. The survey identified 19 per cent of relatives with
spondylolysis, and index patients with each type of spondylolisthesis had relatives with the opposite type.
Index patients with the dysplastic form had a higher proportion ofaffected relatives (33 per cent) than had
those with the isthmic type (15 per cent), but both figures were significantly in excess of the estimated
frequency for the general population of under 1 per cent and 5 per cent respectively.
Spina bifida occulta at the fifth lumbar or first sacral level or both, and lumbosacral s(gmental defects
were commoner amongst all individuals with spondylolysis than amongst unaffected relatives (dysplastic
form 94 per cent, isthmic type 32 per cent, unaffected relatives 7 per cent). However, there was no single
instance ofa neural tube defect (anencephaly, spina bifida with or without meningocele, other generalised vertebral anomalies or spinal dysraphism) amongst 826 first-, second- or third-degree relatives. It is
concluded that the developmental defects of the vertebrae associated with spondylolysis are not
aetiologically related to the neural tube defects. The one in three risk of spondylolysis to near relatives of
patients with the dysplastic form ofspondylolisthesis is emphasised in order that the deformity in their sibs
and children can be recognised at any early age.
Over the past forty years there have been numerous
reports of families with spondylolysis and spondylolis-
thesis (Friberg 1939; Wiltse 1957; Laurent 1958; King
1966; Amuso and Mankin 1967; Turner and Bianco
1 97 1 ; Haukipuro et al. 1 978). More significantly, there
have been some prospective family surveys with
radiographic examination of unselected members
(Baker and McHollick 1956; Wiltse 1960, 1962; Wiltse
and Hutchinson 1965; Yano 1967) and the results have
been remarkably consistent with a frequency of the same
disorder in near relatives of about 27 per cent, a
considerable increase over the estimated frequency of 4
to 8 per cent of most general populations studied (Roche
and Rowe 1952; Barr 1955; Baker and McHollick
1956; Nathan 1959; Yano 1967; Krenz and Troup
1973). An exception to this was established by Stewart
(1 953), who found an unusually high frequency amongst
Alaskan Eskimos. He, Rowe and Roche (1953) and
Kettelkamp and Wright (1971) all noted that there was
no defect at the outset of postnatal life, though some 5
per cent of children were affected by the age of six years
and over 20 per cent by the age of thirty-five. The high
frequency in this race was thought possibly to be due to
unusual mechanical stresses and fatigue fractures of the
pars interarticularis.
bifida occulta at the fifth lumbar or first sacral level
among patients with spondylolysis (Friberg 1939;
Roche and Rowe 1952; Wiltse 1962). Blackburne and
Velikas (1977) found that the risk of a progressive
vertebral slip was greater in patients with a midline
lumbosacral defect than in those without such a defect.
An additional or missing lumbar vertebra or transitional
vertebrae at the lumbosacral level has also been noted as
being more frequent in spondylolytic patients than in the
general population (Friberg 1939; Roche and Rowe
1952).
ated with sacral spina bifida and deficient development
of the superior sacral facet, and Type Ii “spondylolytic
spondylolisthesis” with an elongation or break in the
pars interarticularis. Wiltse, Newman and Macnab
( 1976) have more recently reclassified these two groups
as the dysplastic and isthmic forms of spondylolisthesis
(Figs. 1 to 4).
The aim of the current survey was to take an
unselected group of patients, all of whom had presented
with dysplastic or isthmic spondylolisthesis of the fifth
lumbar vertebra, and to carry out a radiographic review
302 RUTH wYNNE-DAvIE5. J H. 5 SCOTt
THE JOURNAL OF BONE AND JOINT SURGERY
Fig. I Fig. 2
Figure 1-In the common isthmic form of spondylolisthesis the anteroposterior view is normal. Figure 2-The lateral view shows the elongation or break in the pars interarticularis. The line of the superior sacral facet joint approaches the vertical.
of their first-degree relatives (parents, sibs and chil-
dren) looking for a similar defect. It was hoped to
identify the mode of inheritance, distinguishing between
the dysplastic and isthmic types and, in view of the
known association with spina bifida occulta and
vertebral anomalies at the lumbosacral level, to establish
whether spondylolisthesis was aetiologically related to
the neural tube defects of anencephaly, spina bifida with
or without meningocele, multiple segmental anomalies
of the vertebrae and spinal dysraphism.
MATERIAL AND METHOD
A survey was made of forty-seven patients with spondylolisthesis, all living within the Edinburgh area and attending one orthopaedic clinic
(JHSS) Their ages ranged from five to sixty-six years with a mean of
thirty-two years. Twelve had the dysplastic (congenital) type of
spondylolisthesis and thirty-five the isthmic type Patients with
generalised skeletal disease, degenerative spondylolisthesis or that
clearly due to acute injury were excluded
For the genetic survey, the patients were tnitially visited in their
homes and the pedigree obtained. A history of developmental defects
was taken and, where necessary, confirmed from medical records.
Epidemiological information was collected in relation to social and
birth histories, parental age and parity Subsequently all first-degree
relatives willing to help with the survey attended hospital for further
examination and radiography The forty-seven index patients had a
total of 300 first-degree relatives, but only 1 95 were still alive, over
five years of age and available in the district. Of these, 147 (75.4 per
cent) attended for radiography Anteroposterior and lateral views of
the lumbar spine were taken routinely and oblique views in addition
when the diagnosis could not be made on the first two radiographs.
RESULTS
Sex ratio. In the dysplastic group there were seven males
and five females (sex ratio 1 .4), and in the isthmic group
twenty-five males and ten females (sex ratio 2.5), these
ratios being similar to findings in other surveys.
Affected relatives. Only six o the 147 relatives (4 per
VOL. 61-B, No. 3, AUGUST 1979
INHERITANCE AND SPONDYLOLISTHESIS
Figure 3-In the less common dysplastic form of spondylolisthesis the anteroposterior view frequently shows spina bifida
occulta or transitional lumbosacral vertebrae or both. Figure 4-In this lateral view there is a break in the pars interarticularis, but this need not be present. The most important difference between this and the isthmic type is the line of the superior sacral
facet joint, which here approaches the horizontal.
303
spondylolysis; but on radiography twenty-eight of them
were shown to be affected (19 per cent, or nearly five
times as many as suspected on the history alone). This 19
per cent included 22 per cent of parents, 14 per cent of
sibs and 24 per cent of children of the adult index
Table I. Proportions of first-degree relatives with spondylolysis or spondylolisthesis
Patients Parents Sibs Children Total
(12) Dysplastic type 6 of 18 2 of 12 3 of 3 11 of 33 (33.0%)
(35) Isthmic type 5 of 32 7 of 51 5 of 31 17 of 114 (14.9%)
(47) Total I 1 of 50 (22.0%)
9 of 63 (14.3%)
8 of 34 (23.5%)
28 of 147 (19.0%)
seventy years; six were under the age of twenty, eleven
were between the ages of twenty and thirty-nine, and
eleven were forty years and over. There was a higher
proportion of affected relatives of patients with the
dysplastic type compared with the isthmic group (33 and
1 5 per cent respectively). Both these figures are
significantly in excess of the expected frequency for the
general population of approximately 5 per cent (esti-
mated at under 1 per cent for the dysplastic form and 4 to
5 per cent for the isthmic form). Each group of index
patients, dysplastic and isthmic, had relatives with the
opposite type of defect, the dysplastic form always being
less common. Of the eleven affected relatives of the
dysplastic group of patients, ten had an isthmic and only
one a dysplastic defect. In the isthmic group, fourteen of
the seventeen affected relatives had an isthmic lesion
and only three a dysplastic defect (Fig. 5).
FIRST-DEGREE RELATIVES
#{149}/,/,‘Z//ZZZZZA
There was one instance of consanguinity among the
isthmic group, the patient’s parents being first cousins,
but neither they nor a brother had a lesion. There was
one pair of (dizygous) twins in the survey, only one
affected with the isthmic lesion.
Back symptoms in relatives. Only six of the twenty-eight
relatives (2 1 per cent) with a proven spondylolytic lesion
had any symptoms; this was little above the figure of 16
per cent of the remaining relatives who complained of
backache but did not have a defect (twenty of 1 19
individuals). Nevertheless, backache could be ofvalue in
diagnosing spondylolysis under the age of twenty years
since all these younger relatives did have a lesion.
(for the Edinburgh region) would be eleven, or 8 per
cent of the total of 143 sibs (Wynne-Davies 1975).
Epidemiological data. There were no abnormal findings
relating to the pregnancy or birth of these patients,
where these histories were available. Length of gesta-
tion, presentation, birth weight, season of birth, social
class, previous abortions or stillbirths were all within the
expected range. The only finding of probable signifi-
cance was a raised maternal age in patients with the
isthmic type of lesion (28.39± 1 .03 years) compared
with control figures of 26.04±0.22 years
(0.05 >P>-0.025).
Diagrammatic illustration of the proportions of patients and their affected relatives with the dysplastic and isthmic forms of spondylolis-
thesis or spondylolysis.
Eleven of the twelve patients with a dysplastic lesion had
either spina bifida occulta or segmental defects in the
lumbosacral area or both; all four relatives with a
dysplastic lesion had an associated defect here. Of the
patients with an isthmic lesion, eleven of the thirty-five
had such a defect, as had eight of their twenty-four
affected relatives. In contrast, only eight of 119 (6.7 per
cent) unaffected relatives had a defect (Table II). Spina
bifida occulta at the fifth lumbar or first sacral level is
common in the general population, occurring in 25 per
cent or more; other lumbosacral defects occur less
frequently, probably in only 5 to 8 per cent of the
population (Paterson 1893; le Double 1912; Friberg
1939; Friedman, Fischer and Van Demark 1946).
Clearly these additional developmental defects are
particularly associated with spondylolysis and spon-
dylolisthesis, being almost invariable in the dysplastic
type and present in one third of individuals with an
isthmic lesion.
patients or their relatives, and in particular there was no
single instance of a neural tube defect among 826 first-,
second- or third-degree relatives. An accurate compari-
son can be made with the sibs of spondylolisthetic
patients. If these two lesions were aetiologically related,
the expected number of sibs with a neural tube defect
It is clear that a lumbosacral midline lesion or other
segmental defect at this level is common amongst
individuals with spondylolysis and spondylolisthesis, but
since this is not associated with an increased family
frequency of the neural tube defects we conclude that
the two disorders are not aetiologically related.
It seems likely that there is a genetic element to
both the dysplastic and isthmic types of spondylolis-
thesis. Since each defect appears in the other’s family in
a higher proportion than expected for the generil
population, they are likely to be aetiologically related,
but the dysplastic type presents a higher risk to near
relatives (one in three affected) than the isthmic form
(only one in seven affected). This high risk needs
emphasising in order that affected sibs and children of
these patients can be identified at an early age. The
lower proportion of affected relatives among patients
with an isthmic lesion could be due to the fact that it is
not possible to isolate all those patients who have a
simple traumatic (though not acute) lesion from those
Table IL Proportions of index patients and relatives with lumbosacral midline or other segmental defects
Spina bifida occulta (L5 or Si)
Lumbosacral segmental defect
cannot be certainly identified on such a small survey as
this but it probably lies between autosomal dominant
inheritance with reduced penetrance and multifactorial
inheritance. Our view is that there is likely to be a
genetic predisposition to spondylolisthesis; if an associ-
ated lumbosacral spina bifida occulta or segmental
defect is present, it raises the probability of a vertebral
slip which may then be precipitated by quite minor
injury.
REFERENCES
Amuso, S. J., and Mankin, H. J. (1967) Hereditary spondylolisthesis and spina bifida. Journal ofBone and Joint Surgery. 49-A, 507-513.
Baker, D. R., and McHollIck, W. (1 956) Spondyloschisis and spondylolisthesis in children.JournalofBone andJoint Surgery. 38-A, 933-934.
Barr, J. S. (1955) Spondylolisthesis. Journal of Bone and Joint Surgery, 37-A, 878-880.
Blackburne, J. S., and Velikas, E. P. (1977) Spondylolisthesis in children and adults. Proceedings ofthe RovalSocietv a/Medicine. 70, 42 1-422.
Friberg, S. (1939) Studies on spondylolisthesis. Acta Chirurgica Scandinas’ica, Supplement 55.
Friedman, M. M., Fischer, F. J., and Van Demark, R. E. (1946) Lumbosacral roentgenograms of one hundred soldiers. America,z Journal of
Roentgenology and Radium Therapy, 55, 292-298.
Haukipuro, K., Ker#{225}nen,N., Kolvisto, E., Llndholm, R., Norio, R., and Punto, L. ( 1 978) Familial occurrence of lumbar spondylolysis and
spondylolisthesis. Clinical Genetics, 13, 471-476. Kettelkamp, D. B., and Wright, D. C. (1971) Spondylolysis in the Alaskan Eskimo. Journal of Bone and Joint Surgers. 53-A, 563-566.
King, A. B. (1966) Experiences with spondylolisthesis. Bulletin ofthe Johns Hopkins Hospital, 118, 2-9. Krenz, J., and Troup, J. D. G. (1 973) The structure of the pars interarticularis of the lower lumbar vertebrae and its relation to the etiology of
spondylolysis. Journal of Bone and Joint Surgery, 55-B, 735-741.
Laurent, L. E. (1958) Spondylolisthesis. Acta Orthopaedica Scandinavica, Supplement 35.
Ic Double, A. I. ( 1 9 1 2) Trait#{233}des Variations de la Colonne vert#{233}brale cle l’Ho,nme. Paris: Vigot Fr#{232}res.
Nathan, H. (1959) Spondylolysis. Journal of Bone and Joint Surgery, 41-A, 303-320.
Newman, P. H. (1955) Spondylolisthesis, its cause and effect. Annals ofthe Royal College ofSurgeons ofEngland, 16, 305-323.
Newman, P. H. (1963) The etiology of spondylolisthesis. Journal of Bone and Joint Surgery, 45-B, 39-59.
Paterson, A. M. (1893) The human sacrum. Scientific Transactions ofthe Royal Dublin Society, N.S. 5, 123-204.
Roche, M. B., and Rowe, G. G. ( 1 952) The incidence of separate neural arch and coincident bone variations. Journal ofBone and Joint Surgery. 34-A, 491-494.
Rowe, G. G., and Roche, M. B. ( 1 953) The etiology of separate neural arch. Journal of Bone and Joint Surgery. 35-A, 1 02- 1 10.
Stewart, T. D. ( I 953) The age incidence of neural-arch defects in Alaskan natives, considered from the standpoint of etiology. Journal of Bone and Joint Surgery, 35-A, 937-950.
Turner, R. H., and Bianco, A. J., Jun. ( 1 97 1 ) Spondylolysis and spondylolisthesis in children and teen-agers. Journal ofBone andJoint Surgery.
53-A, 1298-1306.
Wiltse, L. L. (1957) Etiology of spondylolisthesis. Clinical Orthopaedics. 10, 48-60.
Wiltse, L. L. (1 960) Spondylolisthesis. Etiology and comparative efficacy of various surgical procedures. Journal of Bone and Joint Surgery. 42-A, 1441.
Wiltse, L. L. (1962) The etiology of spondylolisthesis. Journal of Bone and Joint Surgery, 44-A, 539-560.
Wiltse, L. L., and Hutchinson, R. H. (1965) Spondylolisthesis: etiology and treatment. Journal of Bone and Joint Surgery. 47-A, 1096. Wiltse, L. L., Newman, P. H., and Macnab, I. (1976) Classification of spondylolysis and spondylolisthesis. Clinical Orthopaedics and Related
Research, 117, 23-29. Wiltse, L. L., Widell, E. H., Jun., and Jackson, D. W. ( 1 975) Fatigue fracture: the basic lesion in isthmic spondylolisthesis. Journal ofBone and
Joint Surgery, 57-A, 17-22.
Wynne.Davles, R. ( 1 975) Congenital vertebral anomalies: aetiology and relationship to spina bifida cystica. Journal of Medical Genetics, 12, 280-288.
Yano, T. (1967) Familial incidence of spondylolysis. Journal of Bone and Joint Surgery, 49-B, 390.
VOL. 61-B, No. 3, AUGUST 1979
Related Documents
