lesch - nyhan syndrome was first recognized and clinically characterized in 1964 by lesch and nyhan , observing two affected brothers . lns is a rare x - linked recessive disorder , resulting from a mutation on the gene encoding for the enzyme hypoxanthine - guanine phosphoribosyltransferase ( hgprt ) , located on the long arm of the x chromosome between xq26 and xq27 . the hgprt is an enzyme involved in purine metabolism , which catalyses the condensation reaction which combines phosphoribosyl pyrophosphate ( prpp ) and the purine bases hypoxanthine and guanine to form the respective nucleotides , inosinic acid , and guanylin acid . the hgprt deficiency causes a backlog of guanine and hypoxanthine that oxidize in uric acid and an increase of intracellular prpp with a consequent major production of new purine . it results in an overproduction and accumulation of uric acid , which , if untreated , usually leads to renal failure and death in early childhood . one of the first symptoms of the disease is the presence of orange sand - like crystals of uric acid in the diapers of the affected infant . overproduction of uric acid may lead to the development of uric acid crystals or stones in the kidneys ( nephrolithiasis ) , ureters , or bladder , causing hematuria and increasing the risk of urinary tract infection , of nephrite , and of renal failure . another potential consequence of untreated hyperuricemia is gouty arthritis caused by uric acid crystal deposition in articular cartilage . the affected children appear to be normal for the first few months of life , but hypotonia and development delay are evident from age three to six months . later extrapyramidal involvement with dystonia , choreoathetosis , opisthotonos , dysarthria , dysphagia , and sometimes ballismus becomes evident . the patients also develop signs of pyramidal involvement as spasticity , hyperreflexia , and extensor plantar reflexes . the motor disability is so extensive that most individuals never walk and are confined to a wheelchair . the cognitive disturbs , attention deficit problems , and mental retardation are also present in patients with lesch - nyhan syndrome . the affected children appear normal for the first months of life ; with the eruption of deciduous teeth , they begin to show self - mutilative behavior , biting their oral / perioral tissue and their fingers . the finger nails may be completely ripped , and the self - destructive process involves the bone . in some cases , extensive lesions the secondary infection complicates and retards the healing of traumatic lesions [ 4 , 5 ] . nyhan ( 1997 ) reported that children with lns feel pain and remorse when they mutilate themselves , but they are unable to control and to stop their action . they are usually relaxed when they have physical restraints , instead when it is removed the patients become agitated and their compulsive actions increase . the relationship between the enzyme deficiency and the neurological manifestations in lesch - nyhan syndrome is not so clear . those disorders may be associated with deficits in dopaminergic activity in the basal ganglia ; neurochemical studies of lns patients ' brains show large reductions in da levels , elevated numbers of da receptors , and decreased levels of da transporters . the therapy with allopurinol , a xanthine oxidase inhibitor which blocks the metabolism of hypoxanthine and xanthine into uric acid , can control the overproduction of uric acid , reducing the risk of nephrolithiasis , gouty arthritis , and correlated diseases . the dose of allopurinol has to maintain the uric acid within normal limits ; an excessive allopurinol therapy results in the accumulation of hypoxanthine and xanthine , which could result in xanthine stones . the pharmacological treatment of self - injurious behavior is addressed to control the deregulation in the dopaminergic , opiatergic , or serotonergic systems , as a possible cause of compulsive self - mutilating behavior . the administration of baclofen or benzodiazepines helps in muscle relaxation and keeps the patient calm . the use of hydroxytryptophan together with decarboxylase inhibitor has been proven effective in reducing self - mutilation for a short time . recent therapeutic options also include gabapentin , botulinum toxin a , injected into bilateral masseters , and deep brain stimulation in globus pallidus . the self - destruction behavior should be managed by a combination of physical restraints , behavior modifications , and pharmaceutical therapy , according to olson and houlihan 2000 . in the literature various therapeutic approaches to manage self - destruction behavior are described , but to date the treatment to solve the source of the problem has not been found yet . pharmacological treatment of dopaminergic dysfunction , the possible opiate , and/or serotonin system dysfunction have shown variable successes , but there are disadvantages to pharmacologic treatment , as it usually requires chronic use of the drug that often places the patients in a state of chronic stupor . the use of botulinum toxin a ( btx - a ) should be considered as a good treatment for self - mutilating behavior in lns , but the action of btx - a in decreasing self - inflicted injury is not clear . btx - a may be acting directly on peripheral nerve endings , inhibiting the release of acetylcholine and indirectly on the basal ganglia , resulting in muscle weakness and in decreased behavior . inquiries on btx - a nowadays are not enough and a further study is necessary to define the mechanism of action and the therapeutic results [ 9 , 10 ] . the  deep - brain stimulation  has been performed on a few patients with lesch - nyhan syndrome and some patients experienced a decrease in spastic self - injurious symptoms . published literature suggests that the role of dentist is crucial to prevent and control self - mutilation . in several cases , the extraction of deciduous teeth is adopted in young patient , but the extraction of all teeth is necessary also in permanent dentition . the extraction of only anterior permanent teeth ( incisors and canines ) , as recommended by rosenbloom and other authors , is not effective in preventing self - injury and so all permanent teeth are involved . the extraction of all teeth represents an extreme solution that may cause functional problems and requires a treatment under general anesthesia . to avoid the extractions , a series of intraoral appliance budnick studying a lesch - nyhan syndrome patient , unable to chew his lips for lack of anterior occlusion , decided to create an acrylic splint firstly cemented in the lower arch and secondly in the upper one . he experimented a new technique by covering the posterior teeth to create anterior open bite , eliminating wounds caused by incisors . in the most collaborative patients with few self - mutilations he proposed only normal care of preventive odontology ; in patients showing such a grade of collaboration and of spasticity to allow the intraoral alginate impression , he suggested the use of soft splint without cemented retention which caused hygienic and demineralization problems . finally , in patients with insufficient collaboration the only solution was represented by the extractions of all teeth . a hard acrylic chin - cup with lip extension fitted by means of orthodontic headgear was proposed . the appliance was well tolerated by patients and it guaranteed the health of the oral tissue but increased the dribbling habit with a consequent fungal infection of chins dermis . to solve fungal inflammation the appliance had to be removed . a thin soft resin mouth guard was employed to prevent finger and lower lip self - mutilation in combination with an arm restraint . in six days of treatment and after three months the patient self - mutilations disappeared and he stopped biting himself , also without the mouthguard . in order to prevent dermatitis a soft resin mouthguard not covering the lip was built . it was first cemented and then to increase the retention he preferred heat - cured acrylic resin due to adequate rigidity and he added head strap ; it had to rebuild to be adapted to development of teeth and it was not indicated in periodontal patients . in some resistant casese orthognathic surgery was proposed to create open bite and when the conservative options of treatment failed he suggested the amputation of teeth , as an alternative method to extraction of all teeth to preserve the alveolar bone . the upper and the lower incisors , canines , and the first premolars were performed with formocresol pulpotomies , the crowns were amputated on gingival level , and the dental root canals were filled with light curing glass ionomer cement and polished with softlex discs . the patient was sedated using choral hydrate and hydroxane , but in case of poor cooperation the general anesthesia was indicated [ 1719 ] . a removable acrylic dental appliance was made to create anterior open bite , orthodontic acrylic resin covered the palate , and occlusal surface of posterior teeth and adam 's claps on first upper molar increased the retention . a resin mouthguard thick in posterior part was combined with a lip bumper in order to open anterior bite and to protrude lower lip from the teeth , but this treatment had minimal to partial success . the acrylic resin bite plate 's retention was increased by a combination between adam 's clasps on the premolars and ball clasps among incisors . the operators of the orthodontic ward of gaslini hospital realized a new orthodontic device to preserve oral and perioral tissue of lns patients . at first irreversible hydrocolloid impressions of maxillary and mandibular arches these impressions were finally taken in spite of patient 's lack of compliance ; operators ' persuasive capacity , family , and operators ' efforts to change the negative behavior of m.c . were crucial . on these impressions a plaster model was built , the undercuts were eliminated ( figures 1 and 2 ) , and the orthodontic dispositive was realized by thermoforming disc materials ( with a hard copolyster outer layer and a soft polyurethane inner layer ) ( figure 3 ) , using a positive - pressure thermoformer ( ministar ) ( figures 2 and 5 ) . the hard side was placed in contact with teeth to increase friction and retention ; on the contrary the soft one was placed in contact with antagonist dental arch to prevent traumatic occlusion . the first devices were removed by patients ' tongue , so it was decided to change the dispositive , reducing mucosal flange to prevent the mouthguard 's removal ( figure 4 ) . at the beginning , patients used the device only for few hours , but time by time they were persuaded to wear it longer . at first a thick lower bite was made to produce an anterior open bite ; then it was substituted by a thinner maxillary and mandibular mouthguards well tolerated by the patient also during the meals . after these treatments , the patients were able to wear the device for 24 hours and it guaranteed the health of the oral and perioral tissue . the most common disadvantages of preventive intraoral devices are the design that may cause fungal infections , extensive laboratory time , and difficulty in daily oral care . also frequent adjustments are required and heavy biting forces added to poor cooperation may interfere with impression taking . these devices extend to the vestibule area and the splint that creates an open bite increases the drooling habit with a consequent fungal infection of chin dermis . cemented splint requires an extensive laboratory work , daily hygiene care is difficult , and the demineralization of the teeth is frequent . some patients with lns show a degree of collaboration to allow the intraoral alginate impression , in other lns patients is impossible to have a degree of cooperation on making the intraoral impression ; in fact sedation is sometime necessary . the use of putty - type vinyl polysiloxane impression material or quick alginate to overcome the insufficient patient 's collaboration that makes the intraoral impression very difficult is suggested . it is possible to obtain greater patient 's collaboration thanks to behavioral modification and persuasive capacity of family and operators . the simple intraoral device presented by gaslini operators is easy to fabricate ; it is a mouthguard realized by thermoforming disc and characterized by two different matrices : hard and soft . the hard matrix guarantees a good retention , so during the cementation , the head straps , the splint extension to vestibule area , and the metal clasps are not necessary to give stability . the double matrix device is readily removed for everyday cleaning and the placement is also comfortable . the bite is very thin , it permits that the patient can wear the mouthguard all day , also during the meals , and consequently the drooling habit is not accentuated . the device is built on the patient plaster model ; it can be customized for each individual case . heavy biting force and poor patient 's collaboration may interfere with impression taking . in the case described here the first impression to create an individual impression trays was taken and a second one to fabricate the device . also the work was simplified by the use of quick alginate . in a second moment the efficacy of this device was observed during a period of about 7 years . during these years the major difficulties encountered during this therapy are as follows : necessity of modifying the dispositive to adapt it to the mouth changes , risk of small cracks on the occlusal resin bite that must be often repaired . necessity of modifying the dispositive to adapt it to the mouth changes , risk of small cracks on the occlusal resin bite that must be often repaired . in conclusion the literature analysis demonstrates that the intraoral appliances , despite some limitations , can represent a good alternative option to invasive treatment and a good choice of therapy to limit and to prevent self - mutilative behavior in lns patients . the thin resin mouthguard described was successfully employed to prevent self - mutilation of oral and perioral structures . it represented a conservative solution and a good alternative option to invasive treatment of extracting the teeth or of orthognathic surgery . in addition , the device is easy to build and is well accepted by patient . a good choice of treatment for improving the quality of life of these patients can be represented .
lesch - nyhan syndrome , described in 1964 by lesch and nyhan , is a x - linked recessive disorder , occurring in 1  :  100000 to 1  :  380000 live births . 
 lns is characterized by a decrease in activity of hypoxanthine guanine phosphoribosyl transferase , an enzyme involved in purine metabolism , resulting in overproduction of uric acid . 
 hyperuricemia and neurological features including choreoathetoid spasticity , self - mutilation , and mental retardation clinically characterize this syndrome . in lns patients 
 the typical feature is loss of tissue from biting themselves with partial or complete amputation of fingers , lips , and tongue . 
 the self - mutilation compares with the eruption of the deciduous teeth . 
 several drugs trials have been administered to improve self - destructive behavior and invasive treatment approaches , such as extractions of teeth and orthognathic surgery , have been suggested with variable effectiveness . nowadays prevention is , therefore , the standard of care . 
 the role of dentistry is essential in the management of the self - mutilating behavior , because the teeth represent the main self - injury instrument . 
 this report presents a revision of various therapeutic approaches to manage self - destruction , highlighting the effectiveness of a preventive treatment . 
 it describes a new technique : a resin mouthguard , realized at gaslini hospital , to obtain immediate healing of the oral lesions , confirmed in the follow - up period .