Treacher Collins Syndrome: Genetics, Clinical Features and Management.

Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.

Pediatric unilateral isolated choanal atresia is not associated with mandibular condyle hypoplasia.

PURPOSE: We hypothesized that the ontogeny of unilateral isolated choanal atresia involves a field defect manifesting as ipsilateral mandibular condylar hypoplasia. The topic is important because the mechanism of the unilateral isolated choanal atresia is unknown. MATERIALS AND METHODS: Retrospective self-controlled case series. We included 20 patients (2 males and 18 females, ages 2 weeks to 13 years) with unilateral isolated non-syndromic choanal atresia. We studied their high-resolution computed tomographic scans. Two otolaryngologists measured the largest cross-sectional area of the mandibular condyle in the axial plane perpendicular to the posterior border of each mandibular ramus independently. Statistical significance and inter-rater agreement were calculated with paired Wilcoxon rank sum test and Spearman's non-parametric correlation coefficient respectively. RESULTS: Cross-sectional areas of the condyles ipsilateral to the choanal atresia were not statistically different than those of the contralateral condyle (P = 0.27). Inter-observer agreement of condyle areas was excellent: Spearman's r = 0.85 on the right and r = 0.94 on the left. CONCLUSIONS: In this cohort of children with the rarity of isolated non-syndromic unilateral congenital choanal atresia, no associated mandibular condyle hypoplasia was found. The data suggest that the underlying ontogeny was unlikely attributable to a field defect.

[Transnasal endoscopic surgery of choanal atresia after radiotherapy for nasopharyngeal carcinoma].

Objective: To discuss the effect of endoscopic dilatation and plasty for choanal atresia after radiotherapy for nasopharyngeal carcinoma. Methods: Nineteen patients with choanal atresia who were admitted to the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Nanchang University from Jan. 2011 to Dec. 2018 were reviewed, with 12 males and 7 females aging from 33 to 59 years old. All of the patients had a history of radiotherapy for nasopharyngeal carcinoma and were confirmed by electronic nasopharyngoscope and nasopharyngeal imaging. Among 19 patients, there were 3 cases of unilateral occlusion and 16 cases with bilateral atresia, and all of them were membranous atresia. All patients received the transnasal endoscopic surgery of resecting partial vomer bone while trying to keep normal mucosa tissues and using the septonasal mucoperiosteal flap to repair under general anesthesia. One week after operation, the patients were told to do physiological saline nasal irrigation and received regular clean and observation under endoscope. Descriptive statistical method was used to analyze the outcome. Results: The patients were followed up for 1 year postoperatively by electronic nasopharyngoscopic examination. There was no failure case in all the 19 patients including 16 patients with a wide choana and 3 patients had narrowing of the choana (<50%), with adequate and satisfactory airway. Conclusions: Transnasal endoscopic surgery was an effective treatment for choanal atresia after radiotherapy for nasopharyngeal carcinoma. Application of septonasal mucoperiosteal flap for repairing nasal and nasopharyngeal mucosa would avoid recurrence.

[Malignant infantile osteopetrosis revealed by choanal atresia: A case report]. / Ostéopétrose maligne infantile révélée par une atrésie des choanes : à propos d'un cas.

Malignant infantile osteopetrosis is a rare genetic disease characterized by increased bone density due to osteoclastic dysfunction. We report on the case of a 3-month-old girl who was referred to our hospital by the ENT department for severe anemia in the context of bilateral choanal atresia. Clinical examination showed failure to thrive, anemia, respiratory distress, bilateral choanal atresia, and chest deformation. The abdomen was soft with large hepatosplenomegaly. We noted a lack of eye tracking, no optical-visual reflexes, and left nerve facial paralysis. The blood count showed normocytic normochromic anemia with severe thrombocytopenia. The infectious work-up and blood smears were negative. The skeleton X-ray showed diffuse bone densification of the skull, long bones, pelvis, vertebrae, and ribs. The facial bone CT confirmed membranous choanal atresia. The molecular biology search for the TCIRG1 gene mutation was not available. The patient had supportive treatment (transfusion, oral steroid, vitamin D, oxygen, nutrition). Bone marrow transplantation was indicated but not available. She died at 6 months in a context of severe anemia and bleeding. Malignant infantile osteopetrosis is rare and symptoms are nonspecific. Diagnosis should be considered in young infants presenting refractory anemia, particularly in the context of choanal atresia. Bone marrow transplantation remains the only curative treatment.

Management of the Airway in Apert Syndrome.

The management of the airway in Apert syndrome is complex and multidisciplinary. This rare syndrome, occurring in up to approximately 1 in 65,000 live births, results in airway compromise at various anatomic levels, in addition to abnormal central respiratory drive. Obstructive apneas arise because of decreased airway caliber, which may occur in the form of congenital bony nasal stenosis, choanal atresia, a deviated nasal septum, a narrowed nasopharynx, a thick long soft palate, lateral palatal swellings, and a tracheal cartilage sleeve. Central apneas in Apert syndrome arise because of raised intracranial pressure and/or Chiari malformations. The purpose of this study was to investigate our treatment methods and outcomes in optimizing the airway in this complex, rare and interesting cohort of patients who present with airway compromise. Patients with Apert syndrome were retrospectively evaluated during a period from 1990 to 2013. Treatments for obstructive apnea were dilatation of nasal airways and choanal atresia repair, adenoidectomy, tonsillectomy, early midface advancement, and noninvasive ventilation. The insertion of ventriculoperitoneal shunts, fronto-orbital advancement, and Chiari decompression aid in managing central apneas. The authors present our experience at Alder Hey Children's Hospital, Liverpool, one of the 4 Supraregional Craniofacial Units in the United Kingdom.

Síndrome de CHARGE: una nueva mutación en el gen CHD7 / CHARGE syndrome: A new mutation in the CHD7 gene

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Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997-2007.

Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. The exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n = 117) and isolated choanal atresia cases (those without additional unrelated major defects; n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI = 1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1), and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI = 1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.

[The application septonasal bidirectional mucoperiosteal flap in treatment of refractory choanal atresia in adults].

OBJECTIVE: To explore the effects of septonasal bidirectional mucoperiosteal flap in the treatment of refractory choanal atresia in adults. METHOD: Analysis of 9 cases for choanal atresia was conducted. Two cases were of congenital origin and 7 cases of acquired origin, which was a complication of radiotherapy for nasopharyngeal carcinoma. The patients received transnasal endoscopic surgery using the septonasal bidirectional mucoperiosteal flap, without positioning the postoperative expansion tube. After the operation, the changes of symptoms were observed and the recurrent rate of restenosis or atresia was investigated in the follow-up time. RESULT: The symptoms of nasal obstruction and mouth breathing improved significantly in the 9 patients. At an average follow-up time of 19.3 months, the new forming posterior nare remained patent. The mucoperiosteal flap had no shift or necrosis. No restenosis or atresia happened. Nasal adhesion occurred in two patients. Granulation tissue hyperplasia was found in 1 patient, who underwent endoscopic revision without recurrence. CONCLUSION: The application of mucoperiosteal flap in transnasal endoscopic surgery for the choanal atresia can reduce the incidence of restenosis or atresia. Postoperative expansion tube is not mandatory.

Endoscopic surgery for acquired choanal atresia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study was designed to investigate the role of endoscopic surgery for acquired choanal atresia after radiotherapy for nasopharyngeal carcinoma. METHODS: Twenty-two patients with bilateral or unilateral acquired choanal atresia received transnasal endoscopic surgery with the aid of a powered microdebrider to open atresia choana and received endoscopic sinus surgery simultaneously if they had sinusitis. Merocel epistaxis packing was used to pack the nasal airway for 3 days postoperatively. All of the patients underwent endoscopy regularly for follow-up. RESULTS: Sixteen patients with acquired bilateral choanal atresia and 6 with unilateral choanal atresia were included in this study. The median age was 46 years old (range, 33-65 years). Twenty-one patients had sinusitis. Sixteen patients with bilateral choanal atresia and 4 patients with unilateral atresia had bilateral sinusitis. One patient with unilateral atresia had ipsilateral sinusitis. The mean follow-up period was 35 months (range, 12-72 months) after surgery. Twenty patients were symptom-free after a single operation; nasal obstruction, rhinorrhea, and xerostomia improved significantly for these patients. Two patients had unilateral restenosis that required revision surgery, and both were subsequently free from further restenosis. No complications occurred. CONCLUSION: Acquired posterior choanal atresia after radiotherapy can be successfully treated with transnasal endoscopic resection assisted by a powered instrument without stenting.

[Endoscopic surgical correction of congenital choanal atresia in children].

The authors present a review of the literature and their original data concerning etiology, clinical manifestations, diagnostics, and methods of surgical intervention for the management of children presenting with congenital choanal atresia. The method of endoscopic choanotomy employed by the authors is described.

[Endonasal surgery of choanal atresia].

This paper was designed to study clinical manifestations of choanal atresia (CA) in 11 patients with a view to optimizing methods for medical and diagnostic management of this severe pathology using endonasal surgical techniques. Detailed analysis of possible causes of congenital CA and mechanisms of acquired CA was performed using computed tomography (CT) and retrograde endoscopy with the help of rigid optics. Potential of certain instruments designed and manufactured in Russia for the management of CA is demonstrated, such as retrograde 110o Sekunda endoscope and silicone horseshoe-shaped protectors. An original diagnostic algorithm is proposed allowing for the development of indications for surgical intervention, determination of its extent, and the choice of the post-operative treatment. Improved surgical instruments have been designed for the purpose. A case of hereditary CA in a child and his mother are presented along with results of treatment of nasopharyngeal scleroma in two patients. Clinical manifestations of CA concomitant with scleroma, diphtheria, and chemical chaonal burns are considered.

Repair of acquired posterior choanal stenosis and atresia by temperature-controlled radio frequency with the aid of an endoscope.

OBJECTIVES: To examine the clinical effects of temperature-controlled radio frequency (TCRF) repair of acquired choanal stenosis and atresia with the aid of an endoscope and to discuss the value of acquired choanal stenosis and atresia typing in clinical therapy. DESIGN: Retrospective study. SETTING: Academic otorhinolaryngologic referral center. PATIENTS: Thirty-two patients, aged 32 to 65 years, with acquired choanal stenosis and atresia (from trauma in 9 cases and from radiotherapy after nasopharyngeal carcinoma in 23 cases); 13 cases were bilateral, and 19 were unilateral. INTERVENTIONS: Transnasal TCRF repair with the aid of an endoscope. Acquired choanal stenosis and atresia can be divided into 3 types: type 1, diagnosed within 3 months of the causative trauma or radiotherapy; type 2, diagnosed between 3 and 6 months after the trauma or radiotherapy; and type 3, diagnosed more than 6 months after the trauma or radiotherapy. All patients with types 1 and 2 disease received nasal stents made from Silastic that were fixed with transseptal sutures. However, patients with type 3 disease received no stenting. MAIN OUTCOME MEASURES: The thickness of the stenosis and atresia revealed by computed tomographic scan and the surgical results were also analyzed. There was no significant correlation between them (P > .05). RESULTS: Twenty-nine patients remained free of symptoms for 12 to 42 months after surgery. Three patients required revision surgery, including 2 cases of type 1 disease (3 sides) and 1 case of type 2 (1 side). Two of the patients who underwent revision recovered completely, with no restenosis at 12 months after the second surgery. However, 1 patient with type 1 bilateral atresia experienced another restenosis and required another revision, through a transpalatal approach. There were no postoperative complications. There was no significant correlation between thickness of the stenosis revealed by computed tomographic scan and the surgical results. CONCLUSIONS: We describe a TCRF technique with the aid of an endoscope for choanal repair. In our experience, it has been a highly successful, safe, and effective procedure, with minimal blood loss, swift recovery, and short time of hospitalization. It is important in postoperative care to remove any granulation or polyps at the site of the neochoana. Types 2 and 3 are the best types of disease to treat with this procedure.

Inadvertent intracranial insertion of a soft rubber tube in a patient with Treacher-Collins syndrome: case report and review of literature.

CASE REPORT: An inadvertent insertion of a soft rubber tube into the intracranial compartment in a patient with Treacher-Collins syndrome is reported. The neonate was delivered vaginally at 34 weeks gestation, had bilateral choanal atresia and presented with apnea at birth. An emergency orotracheal intubation was performed, and ventilatory support was instituted. Computed tomography scan of the facial bones showed a bilateral bony choanal atresia, with a thick posterior nasal septum, and complete absence of maxillary sinuses, external auditory canal, middle ear and ossicles, and roof of ethmoid bone. There was a central cleft in the frontoethmoidal area. The inner ear and the semicircular canals were present. The patient underwent successful transpalatal repair with nasal stenting. During surgery, two unsuccessful attempts to negotiate a soft rubber tube through the occluded choana were made. Postoperative magnetic resonance imaging revealed a linear hemorrhagic tract created by the soft rubber tube coursing through the anteroinferior basal frontal lobe, thalamus, basal ganglia and terminating in the occipital lobe. The patient developed bacterial meningitis, communicating hydrocephalus followed by cerebrospinal fluid rhinorrhea. A transcranial repair of the anterior cranial fossa was performed followed by ventriculoperitoneal shunt insertion. Subsequently, he underwent shunt revision for suspected shunt malfunction and developed peritoneal abscess for which the shunt was exteriorized and later removed. An endoscopic third ventriculostomy was performed, and the patient is recovering well. DISCUSSION: The potential implications of an inadvertent foreign body penetration into the intracranial compartment in such a rare event are discussed and the relevant literature is briefly reviewed.

Refractory choanal atresia: what makes a child susceptible? The great Ormond Street Hospital experience.

OBJECTIVE: An outcome analysis of factors that predispose patients to require multiple surgical procedures for choanal atresia repair. DESIGN: Retrospective case note review of choanal atresia patients identified from a prospectively collected database at Great Ormond Street Hospital for Children, London, between 1992 and 2005. SETTING: Specialist centre in pediatric otolaryngology. METHODS: All patients underwent atresia correction by a transnasal approach under endoscopic guidance using a 120 degrees Hopkins rod telescope to visualize the posterior choanae from the nasopharynx. The atretic plate was first perforated using urethral sounds. The posterior choanal opening was subsequently enlarged using the microdebrider drill. Portex endotracheal tubes were used as stents in selected cases. RESULTS: Twenty children (9 male, 11 female) were identified who underwent multiple surgical procedures for restenosis following choanal atresia repair during the study period. The number of procedures per patient ranged from 6 to 42. Approximately half of the patients had other associated major anomalies. CONCLUSIONS: Following primary endoscopic transnasal repair, 9.8% of the patients were considered to have refractory choanal atresia, requiring six or more surgical procedures. Male gender, bilateral disease, associated congenital anomalies, low birth weight, and small stent size are potential risk factors for restenosis of choanal atresia. There was no obvious relationship between the duration of stent placement and restenosis.

Application of holmium yttrium aluminium garnet (YAG) laser in treatment of acquired posterior choanal atresia following radiotherapy for nasopharyngeal carcinoma.

AIMS: To report on the use of holmium yttrium aluminium garnet (YAG) laser in the treatment of acquired posterior choanal atresia following radiotherapy in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: Five patients with acquired bilateral choanal atresia and two with unilateral choanal atresia in the posterior choanae were identified following treatment of nasopharyngeal carcinoma by external radiotherapy, from July 1998 to April 1999. The mean age was 44.6 years (range, 22-65 years). Two patients had stage two and five had stage three disease according to Ho's classification. All patients received 66 Gy of external irradiation delivered to the nasopharynx and a mean dose of 61 Gy (39.8-72 Gy) to the neck. Five patients received an additional external boost of 20 Gy and two received 14 Gy delivered to the parapharyngeal region. Two other patients also received intracavitatory brachytherapy of 18 Gy delivered to the nasopharynx. One patient had concurrent chemotherapy by cisplatinum during external radiotherapy. The mean onset of nasal symptoms was 17 months (range, 2-38 months) following irradiation. All patients were treated by transnasal endoscopic holmium YAG laser resection. Merocel epistaxis packing and a modified nasopharyngeal tube were used to stent the nasal airway for two weeks post-operatively. RESULTS: The mean follow up was 26.8 months (range, 20-32 months) after surgery. All patients were symptom free on follow up. Five patients (71 per cent) retained full patency in the posterior choanae. Two patients (28 per cent) had bilateral mild restenosis in the postnasal space, not requiring revision surgery. The surgical fields were almost bloodless. No adverse post-operative complications occurred, except for delayed nasal septal perforation in one patient and unilateral exposure of the septal cartilage in another; no further treatment was required in either patient. CONCLUSION: Acquired posterior choanal atresia is an unusual complication following radiotherapy, and it can occur early after treatment. It can be successfully treated by transnasal endoscopic holmium YAG laser resection of the scar tissue, with minimal bleeding. A two week period of Merocel nasal packing and nasopharyngeal tube stenting was sufficient to prevent severe restenosis in the posterior choanae; nasal breathing through the tube lumen was possible during this time.

[Choanal stenosis: a rare complication of radiotherapy for nasopharyngeal carcinoma]. / Sténose choanale post-radique: une complication rare de la radiothérapie des carcinomes nasopharyngés.

Choanal stenosis is usually a congenital anomaly in children. Acquired choanal stenosis after radiotherapy for nasopharyngeal carcinoma is a very rare pathology; only two publications report seven cases in the literature. We describe the clinical history, preoperative evaluation, surgical treatment and outcome of a case of acquired choanal stenosis after radiotherapy. The patient, a 56-year-old woman, presented with a history of nasopharyngeal carcinoma (T2- NO-MO) one year before that had been successful treated with radiotherapy (68 Gy). At the end of radiotherapy, she complained of complete nasal obstruction, anosmia and hearing loss due to a bilateral serous otitis media. Bilateral complete choanal stenosis was confirmed by endoscopy and CT scan. Functional endoscopic surgery was performed, and nasal stents were left in place for 3 weeks. One year after, the patient have good airflow, and a patent nasopharynx without choanal stenosis. In conclusion, choanal stenosis is an unusual complication of radiotherapy that can be successfully treated with transnasal endoscopic resection.

Acquired nasal posterior choanal atresia: postradiotherapy.

Reported cases of acquired posterior choanal atresia are very few in the English literature. A case of acquired posterior choanal atresia post radiotherapy is reported which was treated by endonasal endoscopic repair using microdebrider with untoward effect.

Athelia: case report and review of the literature.

The absence of nipple-areola complex is a rare entity and is always associated with other anomalies. This paper described a case of bilateral athelia without other alterations. The atrophy of the dense mesenchyme due to absence of parathyroid hormone-related protein produced in epithelium may lead to nipple involution. Further cases should be studied to corroborate this theory.