The genomic landscape of rare disorders in the Middle East.

BACKGROUND: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. METHODS: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant. RESULTS: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. CONCLUSIONS: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

Facial nerve palsy with acute otitis media during the first 2 weeks of life.

A full-term male newborn presented to us at the age of 2 weeks with left facial weakness that had started at the age of 4 days and steadily progressed over a 10-day period. Physical examination revealed a complete unilateral left peripheral facial nerve paralysis, with an erythematous dull and bulging left tympanic membrane. Computed tomography and magnetic resonance imaging were normal. The patient underwent left myringotomy and placement of a pneumatic equalization tube within 24 hours of presentation. He also received a 5-day course of prednisone and a 2-week course of antibiotics and acyclovir. Improvement of the facial paralysis was rapid, with near-complete resolution at the time of discharge home and complete resolution 6 weeks later. To our knowledge, this is the only reported case of acute otitis media with associated facial nerve palsy in a newborn during the first 2 weeks of life.

Stridor in infants: diagnosis and management.

Stridor is frequently encountered in the pediatric age group and can be alarming to the parents. Many lesions and abnormalities can cause it and the challenge is to pinpoint a specific diagnosis effectively. The patient is usually referred to the pediatric otolaryngologist by the primary care physician who should be aware of the different lesions to avoid any delay in proper management. In the operating room, both the anesthesiologist and the surgeon should cooperate to reach a proper diagnosis or in the extreme situation save the life of the baby.

Intralingual foregut duplication cyst in a newborn.

Congenital lingual cystic masses are challenging entities that can be detected prenatally or discovered in various forms after birth. We report what we believe is only the ninth case of an intralingual foregut duplication cyst that was lined with gastric mucosa. The preoperative evaluation of lingual cystic masses in newborns can include palpation, high-resolution sonography, computed tomography (CT), or magnetic resonance imaging (MRI). However, CT and MRI can pose a risk to the infant because they require sedation in order to properly position the patient for imaging. In our patient, we found that high-resolution sonography was most useful in revealing the nature of the mass as a nonvascular cystic lesion and in delineating its extension. We excised this lesion via bipolar cautery, which we prefer to cold-knife or CO2 laser surgery.

Congenital middle ear cholesteatoma: need for early recognition--role of computed tomography scan.

BACKGROUND: Congenital cholesteatoma (CC) of middle ear is a rare entity that may go undiagnosed for years. Patients with CC who are diagnosed at a later stage of disease have poor outcome. There is controversy regarding the best way to delineate CC preoperatively. More specifically, the need to obtain preoperative computed tomography (CT) scan in all cases of CC is debated. OBJECTIVES: This study was conducted to determine factors that may influence the outcome of surgery in CC as well as the value of obtaining preoperative CT scan in CC. METHOD: A retrospective chart review of all patients with a diagnosis of middle ear cholesteatoma operated on between 1994 and 2000 was carried out. Patients with CC were identified using the criteria proposed by Levenson and Parisier. RESULTS: Thirty-five patients with CC were identified. In 30 (86%) patients, the diagnosis was made during ear examination and the remaining five (14%) patients were diagnosed during myringotomies. Preoperative CT scans were available in 17 patients. The findings on CT scans were classified into four categories based on the ossicular chain and mastoid septae status as well as the presence or absence of middle ear and mastoid opacification. Intraoperatively, 22 (63%) patients were found to have extensive cholesteatomas with or without extension beyond the mesotympanum. Eleven of these 22 patients had ossicular chain erosion and five were later found to have recidivism. Preoperative CT scan accurately predicted the extent of the cholesteatoma seen during surgery in 14/17 (82%) and ossicular chain status in 15/17 (88%), while micro-otoscopy predicted the extent of the existing pathology in only 10/35 (29%). Intraoperative location and size of CC influenced the type of surgical approach, status of ossicular chain, postoperative hearing level and rate of recidivism. CONCLUSIONS: Children still present with late stage CC. Micro-otoscopy is insufficient to clearly delineate the extension of CC. Preoperative CT scan is essential in defining the extent of existing pathology. The intraoperative CC size and location influence the outcome of surgery. Early surgical intervention and long-term follow-up are essential.

Retained ventilation tubes: should they be removed at 2 years?

OBJECTIVES: To assess the complications of ventilation tubes that were retained in children for 2 years or longer and the necessity of removal. DESIGN: A retrospective chart review of all patients who underwent ventilation tube removal from 1997 to 2000, with the exclusion of patients with craniofacial anomalies. SETTING: A tertiary children's hospital. PATIENTS: One hundred twenty-six children with ventilation tubes that were retained for 2 years or longer. INTERVENTIONS: Ventilation tube removal and tympanic membrane (TM) patching. MAIN OUTCOME MEASURES: Otorrhea, formation of granulation tissue, TM perforation, development of cholesteatomas, and tube reinsertion. RESULTS: A total of 126 patients aged 2(1/2) to 14 years (59 girls and 67 boys) underwent removal of their ventilation tubes after 2 years or more. The patients were divided into 2 groups. Group 1 included 67 patients (29 girls and 38 boys) who were younger than 7 years at the time of tube removal. The tubes were retained for 2 to 5(1/2) years (mean retention time, 3.3 years). Group 2 included 59 patients (30 girls and 29 boys) aged 7 years and older at the time of tube removal. The tubes were retained for 2 to 10(1/2) years (mean retention time, 4.2 years). Complications such as otorrhea, formation of granulation tissue, and TM perforation were seen in 10.3%, 13.8%, and 5.2% of the patients with tube retention of 2 to 3 years, compared with 40.0%, 40.0%, and 46.7% of patients with tube retention of more than 5 years. In group 1, transient otorrhea, formation of granulation tissue, and TM perforation occurred in 13.4%, 7.4%, and 6.0% of the patients, respectively, after 2 years of tube retention. In group 2, similar complications occurred in 23.7%, 25.4%, and 27.1% of the patients, respectively. Forty-six patients in group 1 underwent TM patching (31 with paper and 15 with absorbable gelatin film, with a success rate of 91.3%; however, 8 patients (11.9%) required tube reinsertion. In group 2, patching of the TM was done in 40 patients (13 with paper, 24 with absorbable gelatin film, and 3 with fat), with a success rate of 67.5%. Tube reinsertion was necessary in 1.7% of the patients in group 2. No cholesteatoma was encountered. CONCLUSIONS: Higher complication rates are seen in children when ventilation tubes are retained longer than 2 years. Children 7 years and older have a higher incidence of complications from the tube retention than children younger than 7 years. Early removal of ventilation tubes in children younger than 7 years of age, when the risk for otitis media is still present, may result in the need for tube reinsertion.

Powered instrumentation in the treatment of recurrent respiratory papillomatosis: an alternative to the carbon dioxide laser.

OBJECTIVE: To assess the advantages of powered instrumentation vs the carbon dioxide laser in treating patients with juvenile-onset recurrent respiratory papillomatosis. DESIGN: A retrospective study. SETTING: Tertiary care children's hospital. PATIENTS: Patients operated on for juvenile-onset recurrent respiratory papillomatosis between January 1, 1999, and December 31, 2000. Papillomas were excised using the microdebrider in one group and the carbon dioxide laser in the second group. INTERVENTIONS: Direct laryngoscopy and bronchoscopy, suspension microlaryngoscopy, and excision of papillomas by the carbon dioxide laser or the microdebrider. MAIN OUTCOME MEASURES: Operative time and postoperative complications. RESULTS: Seventy-three operations were performed (23 with the laser and 50 with the microdebrider). Sixteen patients were included, 10 with active disease and 5 with disease in remission; 1 was lost to follow-up. They had a mean age of 3.75 years, and the male-female ratio was 7:9. The patients presented mostly with hoarseness (13 [81%]). Four (25%) had soft tissue complications with the laser. The microdebrider was less time-consuming than the laser, although those treated with the microdebrider had more active disease. No factor could be used to measure treatment outcome due to disease variability. Those who were older, female, and African American tended to have less severe manifestations of disease. CONCLUSIONS: The microdebrider proved to be less time-consuming than the carbon dioxide laser when used in patients with juvenile-onset recurrent respiratory papillomatosis. Soft tissue complications were nonexistent. In addition to safety, the microdebrider is more appealing to the surgeon, anesthesiologist, and parents, especially because these children often need subsequent surgical procedures.