Abstract
Alexander disease (AxD) is a rare neurodegenerative disorder caused by mutation of the glial fibrillary acidic protein gene. AxD is characterized by severe motor impairment, intellectual disability, epilepsy, megalencephaly, and seizures. Although palatal tremor and palatal myoclonus have been reported, no other oral findings in AxD patients have been described. Here, we report oral findings from house call dentistry for a 14-year 3-month-old child with AxD. Intraoral findings included gingival hyperplasia, partially impacted teeth, delayed eruption, enamel hypoplasia, macroglossia, anterior open bite, and low tongue posture. This is the first report of oral findings for an AxD patient.
Abbreviations
AxD
Alexander disease
1
Introduction
Alexander disease (AxD) is a rare neurodegenerative disorder that was first reported in 1949 by Alexander [ , ]. AxD is caused by heterozygous mutation in the gene encoding glial fibrillary acidic protein (GFAP) on chromosome 17q21 [ , ]. This disorder is pathologically defined by the characteristic finding of Rosenthal fibers in astrocytes [ ]. Most cases are a result of de novo mutation, but some are inherited in an autosomal dominant manner [ , ].
The prevalence of AxD in Japan is 1 in 2.7 million, with approximately 50 patients suffering from the disease [ ]. The prevalence of AxD in other countries has not yet been reported. Clinical manifestations of AxD in patients with prominent frontal lobe involvement and onset by early childhood include severe motor impairment, intellectual disability, epilepsy, megalencephaly, and seizures [ , , ]. Patients with prominent bulbospinal involvement and onset after school age typically experience pseudobulbar symptoms such as dysarthria, dysphonia, ataxia, autonomic and sleep disturbances, and palatal myoclonus [ , ]. An intermediate form is also known to occur, showing one or more symptoms from both frontal lobe and bulbospinal involvements [ ]. AxD is also classified into infantile, juvenile, and adult forms based on the age at onset [ , ]. Another classification of AxD defines Types I and II [ ]. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features [ ]. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features [ ]. In all classifications, AxD patients with earlier onset show greater disease severity.
To the best of our knowledge, oral findings other than palatal tremor and palatal myoclonus from patients with AxD have not previously been described. In this report, we describe oral findings from a Japanese boy with AxD.
2
Case report
Home call dentistry was requested for a 14-year 3-month-old Japanese boy with AxD and was provided by Hinode Mokomanai Dental Hospital in Sapporo, Japan. The chief complaint was that succeeding permanent teeth had erupted before the deciduous teeth were shed, making tooth cleaning and oral care difficult. His medical history revealed that the patient had been born at 40 weeks gestation weighing 2.9 kg. His head had not been held up and his head circumference had expanded by 4 months old. Magnetic resonance imaging (MRI) of the head at a medical hospital showed findings suggestive of AxD, which the diagnosis confirmed at 8 months old by GFAP analysis. Gene analysis revealed that the patient was heterozygous for 716 G > A, R239H in exon 4 of GFAP . He was bottle fed until 7 or 8 months old, then, after some early weaning experience, was fed through a nasal tube. Gastrostomy had been constructed at 1 year 6 months old, and tracheotomy and laryngopharyngotomy had been performed at 12 years 0 months old. He received nutrition through tube feeding and gastrostomy until 12 years old and thereafter received nutrition only through gastrostomy.
In addition, he was affected by mental retardation, motor retardation, cerebral palsy, and epilepsy. The patient was unable to stand due to muscular hypotonia. He had been receiving sodium valproate, a drug used to treat epileptic seizures, since 0 years 11 months old. The mandibular deciduous central incisor started to erupt at 1 year 2 months old. Family history was unremarkable. Regular house call dentistry has been used since the patient was 5 years 1 month old.
Facies included sunken eyeballs, narrowing of the eye fissures, and a broad nasal bridge. His mouth was often open ( Fig. 1 A).
Intraoral examination at 14 years 3 months old revealed that the upper left canine and lower left second premolar had started to erupt next to the upper left deciduous canine and lower left second deciduous molar, respectively, before those deciduous teeth had been shed ( Fig. 1 B–D). Furthermore, the patient showed gingival hyperplasia, macroglossia, anterior open bite, low tongue posture, and enamel hypoplasia of the upper central incisors ( Fig. 1 ). X-ray images at 14 years 6 months indicated that the roots of the upper left deciduous canine and lower left second deciduous molar had undergone significant resorption and that the roots of both succeeding permanent teeth were complete ( Fig. 2 ).
The treatment plan included extraction of the upper left deciduous canine and lower left second deciduous molar and elimination of gingiva surrounding the lower second deciduous molar. In addition, we considered providing oral management such as removal of dental plaque and tartar, instruction in oral hygiene to the parents once every 3 months, fluoride application to the teeth once every 6 months, and use of oral moisturizing gel because the frequent open mouth led to excessive drying of the intraoral environment.
To facilitate tooth brushing, the upper left deciduous canine and lower left second deciduous molar were extracted using local anesthesia at 14 years 6 months old, and the gingiva around the lower left second deciduous molar was surgically removed. On histopathological examination, the resected gingiva mostly comprised fibrous connective tissues covered by stratified squamous epithelium ( Fig. 3 ). Based on this finding, we diagnosed gingival hyperplasia consistent with gingival hypertrophy.
