Riley-Day Syndrome (Familial Dysautonomia)

Familial dysautonomia is a genetic disorder, inherited in an autosomal recessive manner, caused in almost all cases by a mutation in the gene known as IKBKAP, also called ELP1. It occurs overwhelmingly in people of Ashkenazi Jewish descent, in whom it is one of the more common inherited conditions, though it remains rare in absolute terms. The mutation disturbs the development and survival of certain nerve cells, particularly those of the autonomic nervous system and those of the sensory system.

The consequences of this nerve loss are widespread. Blood pressure may swing unpredictably, swallowing may be uncoordinated, tears may be absent, temperature control may be erratic, and the perception of pain and of where the limbs lie in space may be blunted. These features explain why familial dysautonomia is a systemic condition and not simply an orthopaedic one. Yet running through this systemic disorder is a strong and early tendency to deform the spine.

The reason the spine is so frequently involved lies in the neuromuscular and neuropathic character of the disease. The muscles that surround and balance the spinal column depend on a steady flow of nervous signals to hold the trunk upright and symmetrical. When the sensory feedback that tells the body where it is in space is impaired, and when the control of the muscles that stabilise the spine is uneven, the column is no longer held in balance. Over the years of growth this imbalance allows the spine to drift into a curve.

Spinal deformity is not an occasional complication of familial dysautonomia but one of its defining orthopaedic hallmarks. Across the published series, the large majority of people with the condition develop a curvature of the spine, and the reported prevalence is strikingly high. One of the largest reviews of spinal deformity in the condition, drawn from a major dysautonomia centre, described curvature of the spine in the great majority of patients studied, with figures in the region of eight in ten.

The pattern of the deformity is also characteristic. Many people develop not a simple sideways curve but a kyphoscoliosis, in which the spine bends both to the side and forwards, producing a combined deformity that is more complex than ordinary adolescent scoliosis. The curves tend to begin in childhood, often earlier than the idiopathic scoliosis seen in otherwise healthy adolescents, and they have a strong tendency to progress as the child grows.

Idiopathic scoliosis arises in an otherwise normal nervous system and a structurally normal trunk, tends to appear around adolescence, and follows reasonably well understood patterns. The scoliosis of familial dysautonomia, by contrast, belongs to the family of neuromuscular curvatures. Here the spine deforms because the nervous control of the muscles that balance it is disturbed, and because the sensory feedback that would normally keep the trunk centred is impaired. Curves of this kind tend to start earlier, to be longer and more sweeping in shape, to extend further down towards the pelvis, and to keep progressing for as long as the underlying imbalance persists.

This neuromuscular character has practical consequences. Neuromuscular curves are generally less responsive to bracing than idiopathic ones, because a brace can hold a passive trunk but cannot correct the active imbalance of nervous control that is driving the curve. They tend to involve a longer stretch of the spine, which has implications for any operation undertaken. And they occur in a body that is, in familial dysautonomia, fragile in many other respects at the same time.

A further thread running through the spine in familial dysautonomia is the quality of the bone itself, which is frequently poor. People with the condition have a well-documented tendency towards low bone mineral density and towards fractures, including silent fractures of the vertebrae and ribs that cause no pain because of the blunted sensation. The impaired sensation, disordered autonomic control and altered patterns of weight-bearing combine to produce a skeleton that is often softer and more friable than normal.

This poor bone quality is not a side issue but a central part of why spinal surgery in familial dysautonomia is so demanding. An operation to correct a curvature relies on anchoring metal implants firmly into the vertebrae and on the bone fusing solidly afterwards. When the bone is weak, the anchors hold less securely, the correction is harder to achieve and to maintain, and the fusion is slower and less certain to take.

The foremost perioperative hazard is autonomic instability. Because the autonomic nervous system is profoundly disordered, the body's automatic regulation of blood pressure, heart rate and other vital functions is unreliable, and the stresses of anaesthesia and major surgery can provoke dramatic swings. Blood pressure in these patients can rise and fall steeply and unpredictably during an operation.

A particular feature of the disorder is the dysautonomic crisis, a storm of autonomic overactivity that can be triggered by stress, in which blood pressure surges, the heart races, vomiting and agitation occur, and the whole regulatory system is thrown into turmoil. The major physiological stress of spinal deformity surgery is exactly the kind of trigger that can set off such a crisis. Anaesthesia is a specialist undertaking, demanding meticulous attention to fluid balance, blood pressure and drug choice.

Swallowing in familial dysautonomia is frequently uncoordinated, and the reflexes that normally protect the airway from inhaled food, fluid and secretions are impaired. As a result, material is repeatedly drawn down into the lungs over the years, a process known as aspiration, and the chest in these patients commonly shows the consequences in the form of recurrent infection and scarred, damaged lung.

The spine and the lungs are bound together, because a severe curvature physically restricts breathing at the same time as the underlying disease damages the lung. A patient whose airway is poorly protected and whose lungs are already compromised faces a heightened risk of aspiration during and after anaesthesia, of chest infection, and of difficulty in weaning from breathing support once the operation is over.

When the strands above are drawn together, it becomes clear why spinal deformity surgery in familial dysautonomia is recognised as carrying a high rate of complications. The operation itself is major: correcting a long neuromuscular curve usually involves fusing a substantial length of the spine and anchoring metalwork into many vertebrae. Onto this demanding procedure are layered the particular vulnerabilities of the condition. The bone is often weak, the autonomic system is unstable, the lungs are already compromised and the airway poorly protected, and wound healing may be affected by the altered physiology.

The published surgical experience reflects this. Series describing operative treatment of scoliosis in familial dysautonomia have reported meaningful but limited correction of the curve, friable osteoporotic bone that complicates fixation, and complication rates well above those seen in straightforward adolescent scoliosis.

Plain X-rays of the whole spine, taken in the standing position where possible, are the standard means of measuring the size and shape of the curve and of following it over time. Because the curves often begin early and progress through growth, the spine is typically followed from childhood, with repeated imaging to track whether and how fast the deformity is advancing. Where surgery is contemplated, more detailed imaging such as computed tomography may be used to examine the bony anatomy and to plan implants, and assessment of bone quality, lung function, swallowing and cardiovascular stability forms part of the wider picture.

It is important to be clear that the evidence base for managing the spine in familial dysautonomia is built on observational series, reviews of specialist experience and case reports rather than on large randomised trials, which the rarity of the condition makes impractical.

Bracing has been examined as a means of controlling the curve, particularly in younger children, but the published experience suggests that it is of limited effect, with curves frequently progressing despite a brace. Surgery, in the form of spinal fusion to correct and stabilise the curve, is the intervention described for severe or progressive deformity, and the surgical series report that worthwhile correction can be achieved. Yet the same series are emphatic about the hazards already described, demanding the involvement of an experienced spinal surgeon working alongside specialists in anaesthesia, respiratory medicine and the management of the dysautonomia itself.

The spinal deformity is common, tends to appear early and to progress, and frequently reaches a degree at which it affects posture, sitting balance and, through restriction of the chest, breathing. Where surgery is undertaken, the published experience shows that the curve can be improved and stabilised, but it also shows that this comes with a real burden of risk, arising from the bone, the autonomic system and the lungs together.

This page is general medical education and is not a substitute for individual advice. New or worsening weakness, numbness, saddle numbness or any disturbance of bladder or bowel control requires urgent assessment.

• —Hayek S, Laplaza FJ, Axelrod FB, Burke SW. Spinal deformity in familial dysautonomia. Prevalence, and results of bracing. J Bone Joint Surg Am. 2000;82(11):1558–1562.
• —Bar-On E, Floman Y, Sagiv S, Katz K, Pollak RD, Maayan C. Orthopaedic manifestations of familial dysautonomia. J Bone Joint Surg Am. 2000;82(11):1563–1570.
• —Rubery PT, Spielman JH, Hester P, Axelrod E, Burke SW, Levine DB. Scoliosis in familial dysautonomia. Operative treatment. J Bone Joint Surg Am. 1995;77(9):1362–1369.
• —Albanese SA, Bobechko WP. Spine deformity in familial dysautonomia (Riley-Day syndrome). J Pediatr Orthop. 1987;7(2):174–179.
• —Kaplan L, Margulies JY, Kadari A, Floman Y, Robin GC. Aspects of spinal deformity in familial dysautonomia (Riley-Day syndrome). Eur Spine J. 1997;6(1):33–38.
• —Laplaza FJ, Turajane T, Axelrod FB, Burke SW. Nonspinal orthopaedic problems in familial dysautonomia. J Pediatr Orthop. 2001;21(2):229–232.
• —Fava A, Ciani G, Ghermandi R, Cini C, Maccaferri B, Gasbarrini A. Spine surgery and complication in familial dysautonomia: a case report. Front Surg. 2025;12:1559346.
• —Ngai J, Kreynin I, Kim JT, Axelrod FB. Anesthesia management of familial dysautonomia. Paediatr Anaesth. 2006;16(6):611–620.
• —Weingarten TN, Sprung J, Burgher AH. Perioperative management of familial dysautonomia: a systematic review. Eur J Anaesthesiol. 2007;24(4):309–316.
• —Challands JF, Facer EK. Epidural anaesthesia and familial dysautonomia (the Riley Day syndrome). Three case reports. Paediatr Anaesth. 1998;8(1):83–88.
• —Axelrod FB, Donenfeld RF, Danziger F, Turndorf H. Anesthesia in familial dysautonomia. Anesthesiology. 1988;68(4):631–635.
• —Beilin B, Maayan C, Vatashsky E, Shulman D, Vinograd I, Aronson HB. Fentanyl anesthesia in familial dysautonomia. Anesth Analg. 1985;64(1):72–76.
• —Kazachkov M, Palma JA, Norcliffe-Kaufmann L, et al. Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations. Respir Med. 2018;141:37–46.
• —Hiller N, Simanovsky N, Bahagon C, Bogot N, Maayan C. Chest computed tomography findings in familial dysautonomia patients: a model for aspiration. Isr Med Assoc J. 2009;11(7):393–397.
• —Maayan C, Bar-On E, Foldes AJ, Gesundheit B, Pollak RD. Bone mineral density and metabolism in familial dysautonomia. Osteoporos Int. 2002;13(5):429–433.
• —Hizkiyahu R, Bayme M, Yagel S, et al. Bone mineral density and trabecular bone score in children, adolescents and young adults with familial dysautonomia. Calcif Tissue Int. 2025.
• —Slaugenhaupt SA, Blumenfeld A, Gill SP, et al. Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet. 2001;68(3):598–605.
• —Norcliffe-Kaufmann L, Slaugenhaupt SA, Kaufmann H. Familial dysautonomia: History, genotype, phenotype and translational research. Prog Neurobiol. 2017;152:131–148.
• —Rahman F, Logan SM, Lei XG, et al. IKBKAP/ELP1 gene mutations: mechanisms of familial dysautonomia and gene-targeting therapies. Appl Clin Genet. 2018;11:1–8.
• —Gold-von Simson G, Axelrod FB. Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care. 2006;36(6):218–237.
• —Axelrod FB. Familial dysautonomia. Muscle Nerve. 2004;30(3):352–363.
• —Axelrod FB, Gold-von Simson G. Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet J Rare Dis. 2007;2:39.
• —Dietz J, Axelrod FB, Norcliffe-Kaufmann L, et al. Familial Dysautonomia. GeneReviews. University of Washington, Seattle.

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.