Uncommon sublingual ulceration in an infant

Sir, An eight-month-old girl was referred to our department with an extensive lingual ulceration. The parents noted that she had habitually bitten her tongue since the release of her first teeth at the age of six months. She was a poor feeder and did not sleep well because of the painful lingual ulceration. There was no family history of developmental disorders or congenital syndromes. Intraoral examination revealed a deep, circular, and extensive ulceration of the whole ventral surface of the tongue with intermittent bleeding in the tongue (Figs. 1a – c). An examination of the rest of the intraoral mucosa revealed that the lower central incisors had recently erupted. However, there were two other ulcerations of the palmar surface of the second and third fingers caused by nocturnal finger biting. Neurological examination noted a lack of pain sensitivity related to peripheral neuropathy diagnosed as congenital insensitivity to pain. Based on the clinical features and the particular site on the ventral surface of the tongue against the lower central incisors and ulcerative lesions of the fingers due to self-biting, the lesion was diagnosed as Riga–Fede disease. Because of the size of the ulceration, significant pain during feeding led to inadequate nutrient intake associated with permanent sleep disturbances. Radical treatment was chosen and the lower central incisors were extracted. Topical corticosteroids were prescribed to help with healing. The term Riga–Fede disease has been used to describe a traumatic ulceration that has occurred on the ventral surface of the tongue in newborn babies and infants. It is most commonly related to neonatal or natal teeth but may also occur in infants after the eruption of the primary lower incisors [1]. This benign ulceration occurs as a result of repetitive mechanical trauma caused to the oral mucosal surfaces by the teeth and is most commonly located on the ventral surface of the tongue against the teeth [1,2]. Riga–Fede disease may reveal an underlying developmental or neurologic disorder, including congenital insensitivities to pain [3]. The case of our patient was associated with congenital insensitivity to pain. Failure to diagnose may lead to dehydration and inadequate nutrient intake in the infant because of the significant pain during feeding. No biopsy is needed. The diagnosis of Riga–Fede disease is based on clinical characteristics [1,2]. Treatment should focus on eliminating the source of trauma. Conservative treatment is attempted at first by grinding the sharp edges of the teeth and placing composite resin in a dome shape or by placing a protective ring. If conservative treatment fails to heal the wounds, radical treatment may be necessary, such as extraction of the teeth [2,3]. We believe that Riga–Fede disease must be recognized by clinicians to avoid misdiagnosis and delayed treatment.

Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive sensory neuropathy, was caused mainly by biallelic mutations in the NTRK1 gene. The pathogenesis of CIPA still needs further elucidation.Methods: Here, we recruited a CIPA case and introduced whole-exome sequencing (WES) to identify the causative variation. Subsequently, an in silico molecular dynamic (MD) analysis was performed to explore the intramolecular impact of the novel missense variant. Meanwhile, in vitro functional study on the novel variant from a metabolomic perspective was conducted via the liquid chromatography–mass spectrometry (LC-MS) approach, of which the result was verified by quantitative real-time PCR (qRT-PCR).Results: A novel compound heterozygous variation in NTRK1 gene was detected, consisting of the c.851–33T > A and c.2242C > T (p.Arg748Trp) variants. MD result suggested that p.Arg748Trp could affect the intramolecular structure stability. The results of the LC-MS and metabolic pathway clustering indicated that the NTRK1Arg748Trp variant would significantly affect the purine metabolism in vitro. Further analysis showed that it induced the elevation of NT5C2 mRNA level.Conclusion: The findings in this study extended the variation spectrum of NTRK1, provided evidence for counseling to the affected family, and offered potential clues and biomarkers to the pathogenesis of CIPA.

Comparison of Autistic Individuals Who Engage in Self-Injurious Behavior, Aggression, and Both Behaviors

Background. Two of the most challenging behaviors exhibited by individuals on the autism spectrum are self-injurious behavior (SIB) and aggression. The aim of this study was to identify co-occurring symptoms, behaviors, and medical comorbidities that may provide insight into understanding and treating these behaviors. Method. A large-scale online survey was used to collect data on symptoms, behaviors, and medically related comorbidities commonly reported in individuals with autism spectrum disorders (ASD). Based on responses from 2327 participants, individuals with ASD were divided into four categories: individuals who engaged in SIB only, individuals who engaged in aggression only, individuals who engaged in both behaviors, and individuals who engaged in neither behavior. Results. There were several characteristics and comorbidities associated with those who engaged in SIB only and in aggression only, in addition to those who engaged in both behaviors. Conclusion. The findings in this study provide evidence to support at least two underlying causes of these behaviors (insensitivity to pain and reactions to food) as well as implications for treating them. Furthermore, several behaviors often observed during early childhood may be considered early predictors of these challenging behaviors.

PRDM12 Is Transcriptionally Active and Required for Nociceptor Function Throughout Life

PR domain-containing member 12 (PRDM12) is a key developmental transcription factor in sensory neuronal specification and survival. Patients with rare deleterious variants in PRDM12 are born with congenital insensitivity to pain (CIP) due to the complete absence of a subtype of peripheral neurons that detect pain. In this paper, we report two additional CIP cases with a novel homozygous PRDM12 variant. To elucidate the function of PRDM12 during mammalian development and adulthood, we generated temporal and spatial conditional mouse models. We find that PRDM12 is expressed throughout the adult nervous system. We observed that loss of PRDM12 during mid-sensory neurogenesis but not in the adult leads to reduced survival. Comparing cellular biophysical nociceptive properties in developmental and adult-onset PRDM12 deletion mouse models, we find that PRDM12 is necessary for proper nociceptive responses throughout life. However, we find that PRDM12 regulates distinct age-dependent transcriptional programs. Together, our results implicate PRDM12 as a viable therapeutic target for specific pain therapies even in adults.