Clinical and Genetic Studies of the First Monozygotic Twins with Pfeiffer Syndrome.

Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.940-2A>G) was detected in both twins. The father and both twins shared the same haplotype, indicating that the mutant allele was from their father's chromosome who suffered severe upper airway obstruction and subsequent obstructive sleep apnea. Hypertrophy of nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Increased intracranial pressure in both twins were corrected early by fronto-orbital advancement with skull expansion and open osteotomy, in order to prevent the more severe consequences of increased intracranial pressure, including hydrocephalus, the bulging of the anterior fontanelle, and the diastasis of suture. Conclusions: Both twins carried a FGFR2 mutation and were discordant for lambdoid synostosis. Midface hypoplasia, narrow nasal cavities, and hypertrophic nasal turbinates resulted in severe upper airway obstruction and subsequent obstructive sleep apnea in both twins. Hypertrophy of the nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Fronto-orbital advancement with skull expansion and open osteotomy was performed to treat increased intracranial pressure in both twins. This is the first report of monozygotic twins with Pfeiffer syndrome.

Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations.

Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis−van Creveld syndrome and two patients with Bardet−Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis−van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. Patient 2 had Bardet−Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet−Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.

Treacher Collins syndrome: A novel TCOF1 mutation and monopodial stapes.

Treacher Collins syndrome (TCS: OMIM 154500) is an autosomal dominant craniofacial disorder belonging to the heterogeneous group of mandibulofacial dysostoses. OBJECTIVE: To investigate four Treacher Collins syndrome patients of the Sgaw Karen family living in Thailand. METHOD: Clinical examination, hearing tests, lateral cephalometric analyses, Computed tomography, whole exome sequencing and Sanger direct sequencing were performed. RESULTS: All of the patients affected with Treacher Collins syndrome carried a novel TCOF1 mutation (c.4138_4142del; p.Lys1380GlufsTer12), but clinically they did not have the typical facial gestalt of Treacher Collins syndrome, which includes downward-slanting palpebral fissures, colobomas of the lower eyelids, absence of eyelashes medial to the colobomas, malformed pinnae, hypoplastic zygomatic bones and mandibular hypoplasia. Lateral cephalometric analyses identified short anterior and posterior cranial bases, and hypoplastic maxilla and mandible. Computed tomography showed fusion of malleus and incus, sclerotic mastoid, hypoplastic middle ear space with a soft tissue remnant, dehiscence of facial nerve and monopodial stapes. CONCLUSION: Treacher Collins syndrome in Sgaw Karen patients has not been previously documented. This is the first report of monopodial stapes in a TCS patient who had a TCOF1 mutation. The absence of a common facial phenotype and/or the presence of monopodial stapes may be the effects of this novel TCOF1 mutation.

Human papillomatosis genotyping and severity in patients with recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) and is the most common benign laryngeal neoplasm in children. Although RRP is rarely fatal, the disease requires prolonged, extensive medical and surgical treatment, leading to physical and emotional suffering in affected children and their families. Previous studies show HPV type 11 and type 6 in the lesion of Thai subjects with RRP. There is currently no published data available from Thailand that compares staging and severity with RRP genotypes. OBJECTIVE: To identify the genotypes of human papilloma virus (HPV) isolated from patients with RRP and compare the staging and severity with human papilloma virus genotype. MATERIAL AND METHOD: This prospective study was designed to assess population characteristics and follow the clinical course of RRP from January 2011 to January 2013. At each endoscopic evaluation or debridement, all surgeons to stage each patient's disease severity used a consistent scoring system. The samples were analyzed for HPV genotype. RESULTS: Fifteen Thai children (7 female, 8 male) with respiratory papillomatosis were enrolled. Results showed that HPV type 6 and HPV type 11 caused RRP in 6 (40%) and 9 (60%) of the children, respectively. No co-infection between HPV type 6 and type 11 was found. Overall mean age at diagnosis of patients with RRP was 2.65 ± 0.82 years. The age at diagnosis was significantly different between both HPV genotypes (p = 0.008). The mean disease severity score for HPV type 6 infection was 13.83 ± 9.94, and that of HPV type 11 infection was 27.44 ± 8.24. The mean disease severity score of HPV type 11 infection was significantly higher than that of HPV type 6 infection (p = 0.013). CONCLUSION: HPV type 6 and type 11 caused RRP in Thai children. RRP attributable to infection with HPV type 11 is more aggressive in disease severity and has a shorter life time than HPV type 6 at time of first diagnosis. RRP is an incurable disease that requires long-term medical management. Improved awareness and understanding amongst the Thai population should be promoted to limit the spread of the disease. In addition, further research on the treatment of RRP would benefit patients.

Risk factors for acute pulmonary edema after adenotonsillectomy in children.

OBJECTIVE: Adenotonsillectomy is a common surgical procedure in children. Acute pulmonary edema after this procedure is a rare complication but may be fatal. The factors associated with pulmonary edema after adenotonsillectomy were studied. METHODS: All consecutive patients with an age of less than 15 years who underwent adenotonsillectomy at Chiang Mai University Hospital were enrolled. The study period was from January 2004 to December 2008. Clinical factors were retrospectively retrieved from medical records. Factors associated with acute pulmonary edema after adenotonsillectomy were computed using multiple logistic regression analysis. RESULTS: There were 216 patients who underwent adenotonsillectomy due to airway obstruction during the study period. Five patients were excluded due to incomplete data. Of those included, 129 patients (61.1%) were male with mean age of 6.6 (SD 3.2) years. Four significant factors associated with the development of post-operative pulmonary edema after the adenotonsillectomy were procedure, age, obesity, and pulmonary hypertension. CONCLUSION: Factors associated with acute pulmonary edema after adenotonsillectomy in children were adenotonsillectomy procedure, young age, obesity, or having pulmonary hypertension. Clinicians should be aware of these risk factors while performing adenotonsillectomy in children.