Introduction

Definition of lesch-nyhan syndrome (LNS)

Lesch-Nyhan syndrome is a rare inherited disorder caused by a lack of the HPRT enzyme, resulting in a complete deficiency of purine recycling and excess amounts of uric acid. They often present with elevated uric acid levels, motor dysfunction, developmental delays, and self-injurious behaviour. The less severe forms are inconsistent based on residual enzyme activity and may include hyperuricemia or neurological symptoms without self-injurious behaviour.^1,2

Aetiology and genetic basis

Lesch-Nyhan syndrome is inherited in an X-linked recessive manner due to mutations in the HPRT1 gene located at Xq26-27. Although only one gene is mutated, there are more than 600 different mutations that can contribute to the spectrum of clinical severity detected based on residual enzyme activity. Lesch-Nyhan syndrome presents predominantly in males, while females are usually asymptomatic carriers unless X-inactivation favours the expression of the mutated copy of the gene.³

Rationale and objectives

Lesch-Nyhan Syndrome (LNS) embraces manifestations that are multifaceted and expressed neurologically, dentally, and orthopedically. Oral self-injurious behaviours, along with musculoskeletal deformities, individually as well as collectively, significantly affect a patient's quality of life. It is important to understand all of these factors to provide appropriate and timely interventions. The dental presentations are best managed through preventative and protective measures to prevent or minimise trauma. Orthopaedic issues are managed with physiotherapy, medication, or surgery.

Pathophysiology relevant to dental and orthopaedic health

Uric acid overproduction

Lesch-Nyhan Syndrome originates from mutations to the HPRT1 gene, which leads to an absence of the HPRT enzyme that results in too much uric acid in the body. The excess uric acid in the body can lead to gout, which ultimately causes the painful inflammation of joints, as well as kidney and bladder stones.⁵

Dental problems

A prominent symptom of Lesch-Nyhan Syndrome includes self-injury, usually evident by biting in the area of the lips, tongue, and fingers, causing damage to both the mouth and surrounding areas.² Since medicine is ineffective in stopping this behaviour, dental procedures are necessary to protect the patient. These procedures may include a special mouthguard to minimise injury or possibly remove some teeth.⁵

Orthopedic problems

Excess uric acid can notoriously cause gouty arthritis, which makes joints painful, stiff, and difficult to move. Uric acid can also produce stones in the kidneys or bladder, leading to further complications.⁵

Neuromuscular abnormalities

Lesch-Nyhan Syndrome (LNS) is attributed to a congenital deficiency or complete absence of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), resulting in the abolishment of functions of purine salvage pathways. This deficiency in purine salvage pathways results in high uric acid levels and neurological disabilities. Frequently seen neuromuscular symptoms include hypotonia, which progresses to spasticity, choreoathetosis, dystonia, and other motor control abnormalities.^5,6

Self-injurious behaviour and considerations for dentistry

LNS is characterised by compulsive self-mutilation, such as biting of fingers, lips, and tongue, all of which can lead to remarkably recognisable damage to available oral tissue (lip, tongue, and gingiva) in up to 84% of individuals with LNS. When engaging in dental management for LNS, tooth extraction is not unusual to stave off the possible ongoing damage to tissue as a form of self-mutilation. However, this can have potential psychosocial implications for individuals after extractions. Therefore, during both periods of external and home care, it is possible to utilise intraoral devices such as an acrylic maxillary plate or palatal plate that has often been shown to assist with the reduction of self-injurious behaviours, assist with healing, and has been well accepted by the individual. Ye,t patients displaying oral patterns of self-injury present a challenge for practice, with limited means of intervention leading to variable outcomes regardless of whether a conservative or invasive intervention has occurred.^5,6

Orthopaedic complications and motor dysfunction

Oftentimes, individuals can develop spasticity and involuntary motions that can also inhibit mobility and lead to orthopaedic complications. Post-dental extraction of teeth that had serious mucosal disruption from SIB (self-injurious behaviours), people engage in self-injurious behaviours, which may switch to other areas of the body (eg, fingers) and perhaps increase the chance of injury to parts of their skeletal system⁵

Behavioral manifestations

Almost all people with classic Lesch-Nyhan Syndrome (LNS) exhibit compulsive self-injurious behaviours (SIB), with the majority of SIB involving biting of the lips, tongue, oral mucosa, and fingers. This behaviour typically first appears in early childhood and tends to be extremely resistant to prevention or control.⁷

Aside from self-injury, the involved persons often exhibit other behavioural concerns (problem behaviours) such as aggression, anxiety, attention problems and distractibility, and relationships with others. Aggressive behaviours toward others occur as frequently as self-injurious behaviours. In the milder, attenuated variants of LNS, neurological and cognitive deficits are often less severe, and self-injury is not typically present, but a patient may exhibit attentional deficits and other behavioural disorder problems.⁷

Dental considerations

Common oral manifestations

A key oral feature of Lesch-Nyhan Syndrome is that self-biting behaviour, usually affecting the lips, tongue, cheeks, and sometimes the fingers, is compulsive. Patients often start employing self-biting in early childhood, sometimes beginning before the first year of life and inflicting deep ulcers, lacerations, and continued tissue loss.^6,8 Patients will often develop chronic, non-healing ulcers on the lips and tongue that lead to large amounts of tissue loss. If these ulcers develop on the organ of mastication, secondary difficulties may arise, such as impaired consumption and subsequent weight loss.⁸ Continued self-injury may result in partial or complete destruction of oral or oral-perioral structures, with the change significantly affecting function and aesthetic considerations.^6,8

Preventive and therapeutic strategies

Conservative methods

Customised oral appliances, like mouth guards and bite splints, are commonly used preventative treatments, especially in younger patients or those with less severe symptoms. These devices can protect oral tissues from direct trauma and can make the healing process easier for the existing lesions while also reducing new injuries.^8,9

Pharmacological interventions

Pharmacotherapy with gabapentin, lorazepam, and botulinum toxin injections has been used to reduce self-mutilation behaviours and may help delay (or decrease the need for) surgical dental treatment.⁸

Therapeutic (Interventional) approaches

In the extreme case where conservative interventions are less effective, or the injuries are too severe, multiple or total extractions may be warranted to eliminate or reduce further self-injury and consequential issues. Early extraction in young children has resulted in improved nutritional intake, improved healing, and reduced self-injurious behaviour. Delaying/avoiding surgical intervention increases the potential for increased tissue injury and may complicate management.^8,10

Multidisciplinary approach

Coordinated dental, medical, and behavioural therapies provide the best care for the patient, and well-coordinated approaches are optimal for the individual. Additionally, it is important to continually monitor and modify treatment due to the non-static nature of self-injurious behaviour.^8,9

Anaesthesia and surgical considerations

When conservative or medical management is not effective, dental extractions are required. In many cases, multiple or complete tooth extractions are done to avoid subsequent harm, which gives dental extractions their status as the most common yet irreversible treatment performed. As well as dental extraction, remodelling of the alveolar ridges may also be performed surgically to minimise any further risk of harm. Due to the involuntary movements and behavioural changes associated with LNS, general anaesthesia is usually required for these treatments. Various aspects of anaesthetic management will need to consider the complications of spasticity, dystonia, and airway management. Preoperative evaluation and postoperative monitoring will need to be comprehensive, as patients remain at risk of redirecting self-injury to other areas of their bodies postoperatively. To support positive, patient-centred outcomes, a coordinated, multidisciplinary approach to care from the dental surgeon, anesthesiologist, and neurologist is essential to ensure safety and quality of care.^9,10

Orthopedic considerations

Musculoskeletal and functional abnormalities

Orthopaedic complications in individuals with Lesch–Nyhan syndrome (LNS) are commonly found and are often complex. Up to 50% of individuals experience hip subluxation or dislocation requiring both surgical interventions. Fractures occur frequently due to self-injury and decreased sensitivity, with reports of complete autoamputation in incredibly severe cases. Joint contractures and slight scoliosis may also evolve, which will resemble the contractures noted in spastic cerebral palsy. Infections such as osteomyelitis and septic arthritis may emerge from insensate joints or due to injury.¹¹

Management approaches

Satisfactory orthopaedic surgical interventions, including surgery to the hip, are reported with outcomes comparable to children with other neuromuscular disorders. Fractures would respond to conservative treatment with casting, and hip dislocations would also respond positively to conservative realignment. Early diagnosis and education for the family members are paramount to prevent chronic issues such as Charcot joints and scoliosis, which may necessitate surgery. Special precautions regarding lifestyle behaviours are required to keep track of heterotopic ossification that may develop as a result of surgery or trauma. Appropriate immobilisation is also important following surgery to prevent orthopaedic hardware failure and subsequent fracture. Moreover, protective and multimodal approaches to prevent self-injurious behaviour that leads to orthopaedic damage are vital.^7,11

Multidisciplinary approach

Role of paediatricians, neurologists, dentists, orthopaedic surgeons, psychologists, and physiotherapists
Pediatricians

Paediatricians are usually the first to identify developmental lag and neurological signs, as well as determine diagnosis and pacing of multidisciplinary intervention. Paediatricians continuously track overall growth and development, along with systemic complications such as gout and kidney stones from hyperuricemia⁽¹²⁾.

Neurologists

Neurologists treat motor dysfunction (dystonia and hypotonia) and neurobehavioral symptoms (self-injurious behaviours and cognitive problems) associated with DMD. They provide insight based on pathobiology related to dopamine metabolism and basal ganglia dysfunction.¹³

Dentists

Dentists are crucial to the prevention, as well as the management of oral self-mutilation. Examples of dental intervention can range from protective dental appliances to teeth removals in extreme cases, to curtail tissue damage.¹⁴

Orthopedic surgeons

Orthopaedic surgeons treat musculoskeletal complications due to spasticity and involuntary movements, joint contractures, and deformities, and frequently perform surgeries to fix mobility and function failures.^13,14

Psychologists

Psychologists provide behavioural therapies to address compulsive self-injury and aggressive behaviours, and can provide psychological support to patients and families.¹⁵

Physiotherapists

Physiotherapists create individualised rehabilitation programs to improve mobility, manage spasticity, and maximise physical function, contributing towards improving patients' overall quality of life despite significant challenges regarding motor control.^13,14

Importance of caregiver education and home-based care

The value of educating caregivers

Educating caregivers about the individual's cognitive and behavioural profile can help them provide superior care. Knowledge of cognitive strengths, such as memory and social abilities, can allow caregivers to maximise these skills and use them when communicating with patients. If aware of academic and behavioural weaknesses, caregivers can be proactive when communicating new information, implementing interventions that recognise specific needs, and understanding differing emotional needs. Educated caregivers are better equipped to advocate for educational support personnel with knowledge of Lesch-Nyhan Syndrome and modify their caregiving plan to accommodate personal needs. Educators can then provide a learning atmosphere that meets the student's needs, regardless of the setting¹⁶

Perspective on the educational role of home-care

Home care provides an individualised setting for maximising familiarity, routines, and modes for intervention that adhere to a patient's particular strengths and weaknesses. An educated caregiver within a supportive home atmosphere allows for practice within a social context, promotes emotional stability, and ensures continued learning, all of which will enhance the quality of life for individuals with Lesch-Nyhan Syndrome.¹⁶

Summary

Lesch-Nyhan Syndrome (LNS) is an uncommon X-linked recessive disorder characterised by mutations in the HPRT1 gene, leading to a deficiency of the HPRT enzyme. The deficiency leads to uric acid build-up as well as a range of neurological, behavioural, orthopaedic, and dental issues. Patients with LNS typically display elevated uric acid with motor dysfunctions (spasticity and involuntary movements), developmental delays, and compulsive self-injurious behaviour, mainly composed of oral biting.

Self-mutilation behaviour can result in catastrophic oral tissue destruction requiring prompt surgical dental management with protective mouthguards/frenectomy and/or dental extractions. Orthopaedic problems occur due to multiple gouty arthritis and neuromuscular deterioration that result in mobility impairments, which leads to the risk of injury. Behavioural manifestations of LNS include monthly aggression or anxiety attacks and attentional inadequacies.

The interventions for treating patients with a diagnosis of LNS use a multi-disciplinary approach via medical, dental, and behavioural management means. Conservatively controlling a dental issue along with pharmacotherapy and corrections may always be the first line of management, as, on occasion, surgical options may involve oral extractions via a continuous mono-antiseptic treatment. The nature of anaesthesia care for a patient with LNS requires special attention due to motor and behavioural limitations. Constant attention and interactions can improve the management of patients during the therapy plan to minimise risk and increase oral health and quality of life.