Marfan Syndrome

Marfan syndrome is a heritable disorder of connective tissue. In the great majority of people it arises from a change, or mutation, in a single gene, FBN1, which carries the instructions for making fibrillin-1. Fibrillin-1 is a structural protein that assembles into long fibres called microfibrils, and these microfibrils form part of the elastic framework that gives many tissues their strength, stretch and recoil. Because this framework is found throughout the body, a fault in it has consequences in many places at once, which is why Marfan syndrome is described as systemic rather than confined to any one organ.

The features most often associated with the condition reflect where elastic connective tissue matters most. The wall of the aorta depends heavily on this elastic scaffolding, which is why enlargement of the aorta is the most serious feature of the syndrome. The lens of the eye is held in place by fine connective-tissue fibres, which is why lens dislocation is characteristic. And the skeleton, including the spine, grows under the influence of connective tissue, which is why people with Marfan syndrome are often tall and slender with long limbs and fingers.

The spine is part of this same picture. The vertebrae, the discs between them, the ligaments that bind the column together and the tough lining that surrounds the spinal cord are all connective-tissue structures. When the underlying scaffolding is altered, the spine tends to grow longer and more slender, to curve more readily, and to allow more movement at its joints. Beyond fibrillin-1's structural role, research has shown that it also helps to regulate a signalling molecule called transforming growth factor beta, which influences how tissues grow and remodel.

The diagnosis of Marfan syndrome is made against an agreed set of criteria, most recently the revised Ghent nosology published in 2010. These criteria bring together the major systemic features, particularly enlargement of the aortic root and dislocation of the lens, the family history, the results of genetic testing for FBN1 mutations, and a scored list of smaller, more widespread features that together build a picture of a systemic connective-tissue disorder.

Several spinal and skeletal features contribute to this scored systemic assessment. Scoliosis or a thoracolumbar kyphosis counts towards it, as does a particular chest shape, a reduced ratio of the upper to the lower body, an increased arm span relative to height, and a number of other skeletal signs. Importantly, dural ectasia, the stretching of the lining of the spinal canal, is one of the features that carries weight in this system. In this sense the spine is not a bystander in the diagnosis of Marfan syndrome but contributes several of the threads from which the overall picture is woven.

Scoliosis, a sideways curvature of the spine usually combined with some rotation, is the most common spinal deformity in Marfan syndrome and is reported in a large proportion of those affected, with figures around three in five in many series. Several features tend to distinguish it from the more familiar adolescent idiopathic scoliosis. It often appears earlier in childhood, sometimes in the infantile or juvenile years rather than around adolescence. The curves are frequently more complex, with double or triple patterns, and they are often described as stiffer and less flexible. Crucially, those curves that are going to progress tend to do so more rapidly and more relentlessly, with average progression of several degrees each year in untreated curves of meaningful size.

It is worth noting that the majority of curves in Marfan syndrome remain mild and do not progress to a degree that troubles the person or calls for intervention. The literature describes a spectrum, from minor curves that are followed over time and never become a problem, through to the smaller number of larger, progressive curves that account for most of the surgical interest.

In adolescent idiopathic scoliosis, a back brace is a well-established way of holding a growing curve. In Marfan syndrome the picture is less favourable. Studies of bracing in Marfan scoliosis have reported considerably lower success rates, with one well-known series describing success in only around one in six children. The curves often begin earlier and are more rigid; the connective-tissue laxity may alter the way corrective pressure from a brace is transmitted through the chest wall and ribs; and the progressive forces driving the curve may simply be stronger. The practical consequence is that bracing is less able to prevent a curve from reaching the range at which surgery is discussed.

Alongside scoliosis, Marfan syndrome has a recognised tendency to affect the spine's profile when viewed from the side. A particular pattern is thoracolumbar kyphosis, an excessive forward bend at the junction between the chest and the lower back, where the spine would normally make a smooth transition between its natural curves. This sagittal feature matters because the balance of the spine from front to back is as important as its straightness from side to side. In the context of any deformity surgery, restoring and maintaining this front-to-back balance is recognised as especially important in Marfan syndrome.

Dural ectasia is among the most characteristic spinal features of Marfan syndrome. The dura is the tough outer membrane that encloses the spinal cord, the nerve roots and the cerebrospinal fluid that bathes them. In dural ectasia this membrane is stretched and ballooned outwards, most often in the lower lumbar and sacral region where the pressure of the fluid column is greatest. Being itself a connective-tissue structure, the dura stretches under the steady pressure of the cerebrospinal fluid, gradually widening the dural sac and sometimes hollowing out the back of the vertebral bodies, a finding called posterior vertebral scalloping.

Reported prevalence varies widely with the imaging method and the threshold used, but figures from around two in five up to the large majority of those with the condition are described, which is why it is regarded as so characteristic. Dural ectasia is usually identified on MRI or CT of the lower spine. Many people with dural ectasia have no symptoms from it at all. Where symptoms are described they include lower back ache, headache and other discomforts thought to relate to the altered pressure and the stretched membrane. From a surgical standpoint its main significance is that a stretched, thinned dura is more fragile, which is relevant when any operation in that region is contemplated.

Spondylolisthesis, a forward slip of one vertebra on the one below, is reported more commonly and to a greater degree in Marfan syndrome than in the general population, most often at the junction between the lowest lumbar vertebra and the sacrum. The cervical spine has its own recognised features. Radiological studies describe a tendency to focal kyphosis, increased height of the odontoid peg, basilar invagination and a degree of increased movement between the first and second cervical vertebrae on bending forwards and backwards. Frank instability requiring treatment is uncommon, but the laxity is a recognised reason for care when the neck is positioned, for instance under anaesthesia. Protrusio acetabuli, in which the socket of the hip joint is displaced inwards towards the pelvis, is another skeletal feature that counts towards the systemic score in the diagnostic criteria.

When deformity surgery is considered in Marfan syndrome, several features combine to make it more demanding than the correction of an otherwise healthy spine. The vertebrae themselves are often tall, slender and lightly built. The pedicles are frequently narrow and thin-walled, which makes the secure placement of fixation more exacting. The ligaments are lax and the bone is sometimes less dense, so the anchorage of any construct must contend with tissue that holds less firmly than usual. Dural ectasia adds its own challenge: a stretched, thinned and ballooned dura is more easily torn during surgery, and tears with leakage of cerebrospinal fluid are reported more frequently in Marfan deformity surgery than in idiopathic scoliosis.

The deformities are often larger, stiffer and more complex, with double or triple curves and a significant sagittal component, which is why the literature describes a need for longer fusions, more correction of front-to-back balance and fusion extending further down the spine. There is also a recognised tendency towards higher rates of certain complications, including greater blood loss, dural tears, problems with the fixation holding, failure of the bony fusion to consolidate and loss of correction or imbalance over time, together with a higher likelihood of further surgery.

A defining principle in the surgical thinking around the Marfan spine is that the spine can never be considered on its own. The most serious feature of the syndrome is enlargement of the aorta, which carries a risk of dissection or rupture, and this casts a long shadow over any major surgery. The cardiovascular and pulmonary status is evaluated carefully before any spinal deformity surgery, because a long operation with significant blood loss and considerable swings in blood pressure places demands on a cardiovascular system that may already be vulnerable. The timing and conduct of spinal surgery are weighed against the state of the aorta and any cardiac surgery, and the assessment is shared across the disciplines involved.

Plain X-rays, including standing films of the whole spine and bending views, are the standard means of measuring the size and flexibility of any curve, judging the front-to-back balance, and following whether a deformity is progressing. MRI is the principal way of demonstrating dural ectasia, showing the widened dural sac, any nerve-root pouches and the scalloping of the vertebrae. CT gives the most detailed view of the bony architecture, including the width of the pedicles and the adequacy of the bone for any fixation. These investigations feed into the wider, multidisciplinary picture of a systemic condition.

The outlook for the spine in Marfan syndrome spans a wide range, and it tracks the same spectrum that runs through the whole condition. Many people have only mild spinal features. The larger, progressive deformities are more complex and the surgery more demanding, with higher complication and reoperation rates, yet the literature describes that satisfactory stabilisation and correction can be achieved, and modern series report outcomes that, while harder won, can be comparable in the longer term to those in idiopathic scoliosis. Any individual outlook is a matter for careful assessment by the treating team.

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This information is for general patient education and is not a substitute for an individual consultation. Always seek personalised advice from a qualified spinal specialist.