Abstract
Background
Pitt-Hopkins Syndrome (PTHS) is a rare syndrome caused by heterozygous hypomorphic or null mutation or deletion of transcription factor 4. Characteristic findings have been reported in the mouth and lips, but no studies have investigated the specific size of the teeth or dental arches.
Case presentation
We report a case of an 8-year-old girl diagnosed with PTHS at our hospital. Model analysis of the second molar eruption revealed that the central incisor and dental arch were larger than average for Japanese females.
Conclusion
PTHS patients have wider anterior teeth and dental arches, which may lead to craniofacial anomalies.
1
Introduction
Pitt-Hopkins Syndrome (PTHS) is a rare and severe genetic disease characterized by intellectual disability (ID) and psychomotor and developmental delays with facial dysmorphism. It was first described by Pitt and Hopkins in 1978 [ , ]. Transcription factor 4 (TCF4), a gene located on chromosome 18, encodes a type I basic helix-loop-helix transcription factor and dimerizes with itself. PTHS is caused by heterozygous hypomorphic or null mutation or deletion of TCF4 [ , ]. The prevalence of this syndrome is one case in 400,000 people in the population. It occurs in males and females and is not limited to a specific ethnic background or race [ ].
In modern clinical diagnosis, PTHS falls into the broad category of pervasive developmental disorders and is a syndromic disorder characterized by severe ID, extensive developmental delay, absent speech, distinct facial features, and periods of hyperventilation followed by apnea [ ]. Facial features include a narrow forehead, thin lateral eyebrows, and a specific nose conformation with a broad nasal bridge and ridge, together with a bulbous tip with flared nasal alae. Other features include full cheeks/prominent midface, wide mouth, cupid-bow upper lip and everted lower lip, and mildly cup-shaped and fleshy ears [ , ]. There have been few reports of oral findings in PTHS patients and, to our knowledge, none have provided measurement data on the size of the teeth or dental arches of the patients.
We encountered a PTHS patient who underwent long-term follow-up, enabling us to take oral impressions. In this report, we describe the oral findings using measurements taken from plaster models.
2
Case presentation
A Japanese female aged 6 years and 1 month presented at our hospital with chief complaints of tooth grinding and tooth alignment. She was born at 36 weeks gestation with a height of 38.0 cm and weight of 1508 g. She had ID and had attended a pediatric and rehabilitation center regularly. Her gait was unsteady, and she was of small stature, with a short and curved fifth finger. The height was 103.7 cm and weight was 14.4 kg at that point.
Intraoral examination revealed no dental caries ( Fig. 1 ). However, her erupting mandibular central incisors were crowded, with a deep overbite. Her lack of cooperation meant that the follow-up for oral management was conducted under physical restraint.
At the age of 8 years and 4 months, genetic analysis at the pediatric clinic revealed a TCF4 gene mutation, confirming the diagnosis of PTHS. Although there were no respiratory abnormalities or epileptic seizures at that point, at the age of 10 years she developed the respiratory abnormality of intermittent apnea, which is a characteristic of PTHS.
Physical restraint was no longer required for dental procedures after the age of 8 years because of the patient’s improved cooperation. At 9 years of age, we referred her to the orthodontic department because the anterior crowding had become more severe. Orthodontic treatment was difficult because of the patient’s vomiting reflex; therefore, follow-up was continued using the night guard for tooth grinding. The night guard was made by compressing and shaping DURAN® 1.0mm (JM Ortho, Tokyo, Japan) using BIOSTAR® (JM ORTHO, Tokyo, Japan). The tooth grinding diminished, but orthodontic treatment was postponed.
Subsequent follow-up at the pediatric dentistry clinic showed that the maxillary right second deciduous molar and both mandibular second deciduous molars had replacement-phase defects at the age of 12 years and 1 month; these teeth were extracted under local anesthesia ( Figs. 2 and 3 ). Thereafter, the eruption of the successor permanent second premolar was confirmed.
Considering the patient’s limited cooperation, examinations were conducted separately at several checkups at the ages of 13 and 14 years. We decided to evaluate the oral findings after the eruption of the second molar at the age of 13 years and 7 months ( Fig. 4 ). Intraoral and facial photographs were also taken at 14 years and 3 months ( Fig. 5 ). Although there were no dental abnormalities such as tooth agenesis or microdonts, enamel hypoplasia was detected in the mandibular left second molar and scissor bite was detected in the left first premolar region. The palate was not obviously shallow. In addition, there was no speech, and the tongue was weak and low in position. Facial photographs revealed clinical findings of PTHS: broad nose, full cheeks, cupid-bow upper lip, an everted lower lip, and cupped ears. At the follow-up examination at 15 years and 6 months, no oral problems such as dental caries had occurred ( Fig. 6 ). The enamel hypoplasia of a mandibular left second molar was covered with polycarboxylate cement, and we continue to follow-up the eruption. Although intermittent apnea had been diagnosed, it didn’t occur during regular dental checkup. The height at 15 years and 8 months was 145.0 cm and weight was 43.2 kg.
Impressions were taken for plaster model analysis at the age of 13 years and 11 months ( Fig. 7 ). Dental models of the dental arches revealed an overbite of 2.45 mm and an overjet of 5.40 mm. The mandibular midline deviated 2.15 mm to the right compared with the maxilla, and Angle’s Classification was Class III bilaterally. We compared the mesiodistal tooth width and dental arch width with data from a typical Japanese female [ , ]. The tooth width of the second molars was excluded because they were erupting. The tooth width of the maxillary and mandibular central incisors was 1 S.D. higher than that of typical Japanese females ( Table 1 ). The sum of the tooth width from the mandibular central incisor to the first molar was 1 S.D. higher than the mean value ( Table 2 ). In the maxilla, dental arch width and dental arch length were both 2 S.D. higher than the mean value. The arch width of the mandible was 1 S.D. higher than the mean value, but the arch length was within the average range.
