Nonsyndromic Group Research Articles

Impact of 22q Deletion Syndrome on Speech Outcomes Following Primary Surgery for Submucous Cleft Palate

INTRODUCTION: Patients with 22q deletion syndrome are at increased risk of submucous cleft palate and velopharyngeal insufficiency (1–4). The authors' aim is to evaluate speech outcomes following primary Furlow palatoplasty or pharyngeal flap for correction of velopharyngeal insufficiency in submucous cleft palate patients with and without 22q deletion syndrome. METHODS: Records of submucous cleft palate patients who underwent primary surgery between 2001 and 2010 were reviewed. Data included 22q deletion syndrome diagnosis, age at surgery, procedure, preoperative nasopharyngoscopy and nasometry, speech outcomes, complications and secondary surgery rates. The primary study outcome was a perceptual assessment of resonance within normal limits. Secondary outcomes included the proportions of 22q deletion syndrome and nonsyndromic patients who (1) improved postoperatively with regards to perceptual assessment; (2) experienced a complication following surgery; or (3) required revision surgery for persistent velopharyngeal insufficiency. RESULTS: Seventy-eight submucous cleft palate patients were identified. Twenty-three patients had 22q deletion syndrome. Fewer 22q deletion syndrome patients obtained normal resonance on perceptual assessment compared to nonsyndromic patients (74 percent versus 88 percent). A similar difference existed based on postoperative nasometric scores. Among 22q deletion syndrome patients, similar success rates were achieved with Furlow palatoplasty and pharyngeal flap. No difference in the proportion improved postoperatively was noted between 22q deletion syndrome and nonsyndromic groups. One complication was experienced per group. More revision surgeries were indicated in the 22q deletion syndrome group (17 percent) compared to nonsyndromic group (4 percent). Median times to normal resonance for 22q deletion syndrome and nonsyndromic patients were 150 weeks and 34 weeks, respectively (Figure 1). Adjusting for multiple variables, 22q deletion syndrome patients were 3.6 times less likely to develop normal resonance.Figure 1: Kaplan-Meier analysis comparing unadjusted probabilities of developing normal resonance on perceptual speech assessment for 22q deletion (red) and nonsyndromic (blue) patients. Censored data are depicted by open circles. Median times to normal resonance for 22q deletion syndrome and nonsyndromic patients were 150 weeks and 34 weeks, respectively.CONCLUSION: Careful selection of Furlow palatoplasty or pharyngeal flap for primary repair of submucous cleft palate is highly effective in 22q deletion syndrome patients and yields results approaching those of nonsyndromic patients.

Raised Intracranial Pressure Is Frequent in Untreated Nonsyndromic Unicoronal Synostosis and Does Not Correlate with Severity of Phenotypic Features

In a small number of children with unicoronal synostosis, the phenotype is mild and the aesthetic benefit of surgical correction is potentially outweighed by surgical risk. Raised intracranial pressure, however, would necessitate intervention. The authors documented the incidence of raised intracranial pressure in children with mild features and/or parental reluctance to proceed directly to surgery. A retrospective review of all children with (1) a clinical diagnosis of nonsyndromic unicoronal synostosis; (2) unicoronal synostosis confirmed on computed tomographic scanning; (3) negative family history for unicoronal synostosis; and (4) negative genetic screening (including P250R encoded by FGFR3, exons IIIa and IIIc in FGFR2 and TWIST1) was completed. Of the 80 children studied, seven (9 percent) underwent formal intracranial pressure monitoring because of a combination of mild clinical features (n = 4) and/or parental reluctance to proceed with surgery (n = 3). Intracranial pressure monitoring was reported as high in three (42 percent), borderline in two (29 percent), and normal in two patients (29 percent). The findings did not correlate with the degree of clinical deformation or age at presentation. There was little correlation with clinical and radiographic features of raised intracranial pressure in this genetically screened nonsyndromic group. High or borderline raised intracranial pressure was present in five of seven cases. The risk did not correlate with degree of deformity or age at presentation. Formal intracranial pressure monitoring should be considered in all children with unicoronal synostosis not proceeding directly to surgical intervention, in combination with routine long-term follow-up and repeated intracranial pressure monitoring where indicated. Risk, V.

Diagnosing Arthrogryposis Multiplex Congenita: A Review

Arthrogryposis multiplex congenita (AMC) refers either to a syndromic or to a nonsyndromic group of conditions with varied etiology and complex clinical features, including multiple congenital contractures in different body areas. Its etiology still remains unclear but generally any cause that leads to reduced fetal movement may lead to congenital contractures and in severe cases to fetal akinesia deformation sequence (FADS). It affects approximately 1 in 2-3000 live births with an approximately equal gender ratio. There are many known subgroups of AMC differing in signs, symptoms, and causes. The primary diagnosis is made when a lack of mobility and an abnormal position is noted in routine ultrasound scanning. Early diagnosis, prenatal evaluation, and further surveillance via image scanning (ultrasound and MRI) give the opportunity for family counseling concerning neonatal morbidity and mortality and labor or delivery planning. Better understanding of the ultrasound findings and the etiology of this clinical situation offers the opportunity for careful prenatal assessment.

Genetic Syndromes and Outcome After Surgical Repair of Pulmonary Atresia and Ventricular Septal Defect

Genetic syndromes, especially 22q11 deletion (del22q11) syndrome, are common in patients with pulmonary atresia and ventricular septal defect (PA-VSD), but their association with long-term outcomes varies. The purpose of this study was to evaluate the long-term outcome after complete repair of PA-VSD and to determine the impact of genetic syndromes. We reviewed our experience of 125 patients with PA-VSD who received primary or staged repair between 1978 and 2010. Evaluations for genetic syndromes included clinical features, cytogenetic analysis, and fluorescence in situ hybridization or multiplex ligation-dependent probe amplification. Genetic syndromes were documented in 26 patients (20.8%), including del22q11 in 16 patients, trisomy 21 in 2 patients, and other syndromes in 8 patients. The prevalence of hypoplastic pulmonary arteries was not significantly different between the syndromic and nonsyndromic groups. After 1,069 patient-years of follow-up, 20-year survival was 90% ± 6% in patients without syndromes and 14% ± 23% in patients with syndromes (p < 0.01). Multivariate analysis identified the presence of a genetic syndrome as an important risk factor for hospital and late mortality. Subgroup analysis showed that genetic syndromes other than del22q11 were associated with worse outcome. The rate of 10-year freedom from cardiac reintervention after repair was 53% ± 11%, with hypoplastic pulmonary arteries before repair as a major risk factor (p = 0.02). Genetic syndromes significantly affect survival after repair of PA-VSD, whereas genetic syndromes do not represent additional risk for reintervention. Repair is feasible in patients with syndromes, but suboptimal long-term outcome should be addressed when counseling parents.

Facial Growth in Patients with Apert and Crouzon Syndromes Compared to Normal Children

To evaluate vertical and sagittal facial growth in children with Apert and Crouzon syndromes and compare it to the growth patterns of a nonsyndromic control group. Case-control study. Department of Orthodontics, Children's Hospital Erasmus Medical Centre, Sophia, Rotterdam, The Netherlands. Sixty-two patients (37 patients with Crouzon syndrome and 25 patients with Apert syndrome) born between 1971 and 2001 (age range 3.9 to 32 years) and 482 nonsyndromic children as a control group. Lateral cephalograms performed prior to any midfacial surgery of 62 patients and 482 nonsyndromic children were traced and horizontal and vertical measurements were digitized. Cephalometric measurements of SNA, SNB, ANB, NSMe, and SN/palatal plane angles and lower facial height ratio. Horizontal measurements for the syndromic groups showed no change in SNA angle during growth. SNA angles were lower in patients with Apert syndrome compared to patients with Crouzon syndrome. The syndromic groups showed smaller values for ANB angles compared to the nonsyndromic group. Vertical measurements showed increased lower facial height ratios for the syndromic groups compared to control subjects. There was an increasing counterclockwise rotation of the palatal plane in relation to the anterior cranial base in syndromic patients. NSMe angles among the three groups were not significantly different. Based on the growth differences identified, the sagittal and vertical jaw relationships differ in patients with Crouzon syndrome, patients with Apert syndrome, and control subjects. Syndromic patients show aggravation of midfacial underdevelopment and anterior rotation of the mandible.

Craniofacial morphological differences between Down syndrome and maxillary deficiency children

Maxillary deficiency is one of the facial features of Down syndrome (DS). Differences in craniofacial morphology between DS and nonsyndromic skeletal Class III malocclusion with maxillary deficiency remain unclear. This study compared the craniofacial differences of white male children from Central-Western Brazil with DS (n = 30, mean age: 8 years 3 months), skeletal Class III profile with maxillary deficiency (n = 30, mean age: 7 years 9 months), and skeletal Class I profile (n = 30, mean age: 8 years 2 months), using lateral cephalometric radiographs. The differences among the three groups were compared with analysis of variance and Tukey's tests. The DS group showed reduced anterior cranial base (S-N, P < 0.001] and facial dimensions (Co-Gn, N-Me, N-ANS, and ANS-Me, P < 0.001), except in posterior dimensions (S-Go, P < 0.005; Ar-Go, P > 0.005). Maxillary length (Co-A, P < 0.001) and facial convexity (NAP, P < 0.005) were reduced when compared with the control group, although maxillary position to cranial base (SNA, P < 0.005) was within the normal range. A flattened cranial base (BaSN, P < 0.001) also contributed to differentiating DS from nonsyndromic groups. The group with maxillary deficiency showed a more unfavourable maxillomandibular relationship (MMD, P < 0.001) and a mandibular protrusion (SNB, P < 0.001). Subjects with DS differed from Class III with maxillary deficiency with respect to the flatter cranial base and reduced maxillary length. Maxillary deficiency was not so expressive in the face of DS subjects because of the overall reduction in craniofacial dimensions.

Patterns of cardiac and extracardiac anomalies in adults with tetralogy of Fallot

tetralogy of Fallot (TOF) is a complex congenital heart disease with clinical and genetic heterogeneity. Of the few known causes, 22q11.2 deletion syndrome (22q11DS) is the most common. We sought to define other clinical subgroups by focusing on cardiac and extracardiac features. we prospectively screened a cohort of adults with TOF using an established protocol by which subjects were categorized as "syndromic" if they had at least 2 of 3 features: dysmorphic facies, learning difficulties, or voice abnormalities. We then compared the prevalence of cardiac and extracardiac features between subjects in the syndromic group (n = 56) and 112 age- and gender-matched subjects who did not meet our syndromic criteria. the syndromic group was more likely than the nonsyndromic group to have pulmonary atresia and/or major aortopulmonary collateral arteries (25% vs 13%, P = .04). There was a trend toward a higher prevalence of one or more major congenital extracardiac anomalies, primarily involving the musculoskeletal and genitourinary systems (25% vs 13%, P = .06). Later-onset conditions, including neuropsychiatric disorders (32% vs 17%, P = .03), thyroid disorders (20% vs 4%, P = .001), and hearing deficits (20% vs 0, P < .001), were more common in the syndromic group. The syndromic group tested (n = 50) had neither 22q11.2 deletions nor karyotypic anomalies. similar to 22q11DS, adults with TOF meeting screening criteria for a possible genetic syndrome are enriched for more severe cardiac disease and late-onset extracardiac features. Increased awareness of this subgroup with a multisystem condition may be helpful for identifying individuals for referral to medical genetics and optimizing management.

The screening of four common deafness gene mutations spectrum in Uigur and Han patients with non-syndromic deafness in Xinjiang Autonomous Region

Objective To investigate the prevalence and frequency of the common mutations in Uigur non-syndromic deafness group in Xinjiang Uigur Autonomous Region of China, by means of screening nine mutations of four known deafness genes. Methods One hundred eighty-four Uigur patients and 133 Han patients with non-syndromic hearing loss were enrolled in this study. The screening was performed on GJB2, GJB3, mtDNA 12S rRNA and SLC26A4 deafness genes of 35delG, 176de116,235de1C ,299-300delAT,538C ＞ T, 1555A ＞ G, 1494C ＞ T,2168A ＞ G, IVS7-2A ＞ G in these two groups, by means of genic microarray. Results The totlal mutation rate found in the Uigur deafness groups was 12. 50%, significantly different from that in the Han deafness groups (30. 83% ,χ2 = 16. 092 ,P ＜0. 01 ). The GJB2 mutation rate in the Uigur deafness groups was 9. 24%, not significantly different from that in the Han deafness groups ( 14. 29% ,χ2 = 1. 953 ,P ＞0. 05 ). The mutation rate of SL C26A4 was 1.63% and 13.53% respectively in Uigur and Han deafness groups, and has significant difference (χ2 = 17. 683, P ＜ 0. 01 ). The mt DNA 12S rRNA mutation rate in the Uigur deafness groups was 1.63%, not significantly different from that in the Han deafness groups (3.01%, χ2 = 0. 175, P ＞ 0. 05 ). The GJB3 mutation rate of these two deafness groups was very low, shown as 0. 75% and 0 respectively. Conclusions The mutation rate of common deafness genes is lower in the Uigar nonsyndromie deafness group, and the mutation rate of SLC26A4 genes is significantly lower than that in the Han deafness groups. The most common mutation in four known deafness genes is GJB2, whose favorite spots are 235delC and 35delG. Key words: Deafness; Connexins; Membrane transport proteins; RNA, ribosomal; Mutation; Oligonucleotide array sequence analysis

Dental caries prevalence in children with cleft lip/palate aged between 6 months and 6 years in the West of Scotland

To compare the prevalence of dental caries in children with cleft lip/palate with national data at the same age. Ethical approval was granted from the West of Scotland Ethics Committee. Children attending the Oral Orthopaedic Clinic were examined for caries according to the criteria of the British Association for the Study of Community Dentistry (BASCD) by two trained and calibrated examiners (KB, RW). Subjects were divided into five age groups: 0.5-1.49; 1.5-2.49; 2.5-3.49; 3.5-4.49 and 4.5-6.0 years. Mean dmft scores were compared with available national data (National Dental Inspection Program of Scotland) for nursery [NDIP 3-year-old survey 2008, unpublished] and 5-year-old children in Scotland [NDIP, 2008]. 209 subjects were examined (participation rate of 87.4%); 45.9% were female, 54.1% male; 21 children (10%) had a recognised syndrome and were reported separately. Cleft Palate (CP) was the most commonly occurring cleft in both syndromic and non-syndromic groups, followed in decreasing numbers by Unilateral Cleft Lip and Palate (UCLP), Bilateral Cleft Lip and Palate (BCLP), Unilateral Cleft Lip (UCL) and Bilateral Cleft Lip (BCL). The only age group with a significantly higher level of dental caries compared with national data was the 4.5-6.0 year-olds where only 37.2% of the children with clefts were caries free compared with the national figure of 57.7% (p=0.004). This same age group had a mean dmft for the cleft group of 3.24 compared with 1.86 nationally. The other age groups had similar dmft and percentages of subjects caries free compared with the national data. The differences did not reach significance. Caries was more common in the anterior teeth of the youngest two age groups, but in the posterior teeth of the two oldest age groups. By the age of 4.5 years, children with cleft lip/palate in the West of Scotland have significantly more caries than their non-cleft peers.

Velopharyngoplasty for Noncleft Velopharyngeal Insufficiency

To evaluate the results of velopharyngoplasty for velopharyngeal insufficiency (VPI) in relation to 22q11 deletion or nonsyndromic VPI. Retrospective study. Academic medical center. Eleven of 45 patients with 22q11 microdeletion (group 1) and 9 patients without 22q11 microdeletion (group 2) with noncleft VPI (hypoplastic velum or hypodynamic velopharynx and deep pharynx) underwent velopharyngoplasty (midline pharyngeal flap with superior pedicle). Exclusion criteria included cleft palate, submucous cleft palate, all syndromic cases, and all associated malformations (except those related to 22q11 microdeletion in patients with DiGeorge syndrome). Speech assessment before surgery using the Borel-Maisonny scale and at 9 months and 24 months after surgery. Velopharyngeal insufficiency was classified as normal, inconsistent, mild, moderate, and severe. Before surgery, in group 1, 3 patients had mild and 8 had severe VPI, and in group 2, 1 had mild and 8 had severe VPI. Postoperative outcomes at 9 months showed that in group 1, 2 patients had excellent results (normal and inconsistent) and 9 had mild VPI, while in group 2, 6 patients had excellent results and 3 had mild VPI (P = .03). Postoperative outcomes at 24 months showed that in group 1, 10 patients had excellent results and 1 had mild VPI, while in group 2, 8 patients had excellent results and 1 had mild VPI. Surgical treatment of noncleft VPI by pharyngoplasty was efficient in 10 of the 11 patients (91%) in the 22q11 group and in 8 of the 9 patients (89%) in the nonsyndromic group. Postoperative remission took longer for patients with the 22q11 microdeletion than for the control group. However, long-term results following surgical treatment were equally good in the 2 groups.

Surgical Outcomes for Velopharyngeal Insufficiency in Velocardiofacial Syndrome and Nonsyndromic Patients

To compare speech outcomes after operative intervention for velopharyngeal insufficiency between velocardiofacial syndrome patients and nonsyndromic patients. Retrospective cohort study. Tertiary academic center. Cohorts of 14 velocardiofacial syndrome and 15 nonsyndromic patients without overt cleft palate who underwent operative procedures to correct velopharyngeal insufficiency. All velocardiofacial syndrome patients were positive for 22q11.2 microdeletion by fluorescent in situ hybridization and possessed phenotypic features of velocardiofacial syndrome. Operative procedures, including sphincter pharyngoplasty, Furlow palatoplasty, or both, were selected based on preoperative endoscopic assessments of velopharyngeal motion and residual gap size and shape, as well as velocardiofacial syndrome status. Five single and 9 combined procedures were performed in the velocardiofacial syndrome group, whereas 13 single and 2 combined procedures were performed in the nonsyndromic group. Pre- and post-op evaluation was conducted by a speech pathologist. Assessment parameters scored on a numerical scale included speech intelligibility, resonance, nasal air emissions, and overall severity of velopharyngeal insufficiency. Postoperative complications were recorded. Most velocardiofacial syndrome patients and nonsyndromic patients demonstrated significant improvements in all parameters. Comparison of the two groups demonstrated similar improvements in both. Changes in speech resonance were significantly different between the two groups, whereas other speech parameters did not reach significance. There was no difference in airway complications between groups. Velocardiofacial syndrome patients may have comparable outcomes to nonsyndromic patients in selective surgical management of velopharyngeal insufficiency. In addition, the data demonstrate the efficacy of a single-stage combined procedure without increased morbidity.

747. Identification and Characterization of Mutations within the Coxsackievirus and Adenovirus Receptor (CAR)

The Coxsackievirus and Adenovirus Receptor (CAR) is both a virus receptor and an adhesion protein. The genomic localization and a previously described interaction with the PDZ domain containing protein Harmonin led us to investigate whether CAR is the gene responsible for Usher syndrome type 1E. Usher syndrome is the most frequent genetic cause of deaf-blindness in humans and is a result of mutations within several interacting proteins including molecular motor, scaffolding and adhesion proteins. A total of 271 non-syndromic deaf and 10 Usher 1 patients were evaluated for mutations within the exonic regions of CAR. No mutations were found in the Usher patients, however, two haploid mutations were discovered in the non-syndromic group (L255H and P356S). Since these are the first two amino acid changing mutations found in CAR, they were investigated for cell surface expression, viral receptor activity and localization after creating the mutations by site-directed mutatgenesis. Both mutant forms of CAR were present at the cell surface and behaved as receptors for Adenovirus. Interestingly, these mutants ran at a molecular weight approximately 10 kDa greater than CAR. In vitro translation of the cDNA resulted in identical products suggesting an altered post-translational modification such as ubiquitination. In summary, CAR is a highly conserved gene in which only two exonic conserved polymorphisms have been described to date. Here we describe the first two mutations found in this gene and we will investigate the functional consequences of these two mutations.

Evaluation of deaf children in a large series in Turkey

Evaluation of the deafness etiology, ear examination findings and hearing levels of deaf children in a large series. We studied 840 deaf primary school children (486 male, 354 female, mean age 12.69+/-3.52, range 5-22). A questionaire investigating the prenatal, perinatal and postnatal etiological causes was prepared and pedigree analysis was performed. After ENT examination, odyologic tests were performed. The etiological features of deafness were found for genetic causes as 429 cases (51.1%), 127 children (15.1%) for acquired group and 284 children (33.8%) for unknown group. We confirmed 136 (15.5%) syndromic deaf children and 19 of them (13.9%) were autosomal recessive (AR), 105 of them (77.2%) were autosomal dominant (AD), six (4.4%) of them were X-linked. Two hundred and ninety-three deaf (33.4%) children were in the familial nonsyndromic group. In this group, the inheritance of 255 (87%) were AR, 23 (7.8%) were AD and 15 (5.2%) were X-linked recessive. Febrile convulsion was identified as the most common etiology in 36 (4.3%) cases in the acquired group. Three hundred and twenty-two (67.7%) children had profound HL (above 91 dB), 111 (23.3%) had severe HL and 43 (9%) had moderately severe HL. Sensorineural HL was found in 439 (92.2%) and mixed type hearing loss was seen 37 (7.8%) of 476 cases. We found many major and minor abnormalities and ocular, ear and dental pathologies. The prevalence of ear diseases was found in 203 (24.2%) of children. Impacted wax was found in 80 (9.5%) of 840 children with otoscopic examination and was the most common pathology, retraction in 70 (8.3%) and perforation in 15 (1.8%) followed it. Preventable ear disease are important health problems among school children for the deaf because these diseases can affect the real level and type of deafness, so determining early diagnostic criteria, ear diseases and minor abnormalities is important for early rehabilitation. Syndromes can be prevented in pregnancy, infections can be prevented in prenatal or postnatal period but unknown group cannot be prevented although the unknown etiology can be reduced by multidiciplinary approach.

Clinical implications of molecular genetic research in otorhinolaryngology

Molecular-genetic research in Otolaryngology has seen a rapid advancement during the last ten years, especially in the fields of otology and head and neck tumors. The results of this basic research have now started to be implemented in the clinic. In otology the understanding of auditive function has dramatically improved. The syndromic and non-syndromic forms of hereditary hearing impairment can be subdivided into their underlying genetic defects, as more and more genes are identified. Diagnostic of syndromic hearing loss has been improved and can be done earlier. But the molecular-genetic analysis is still time-consuming and difficult. Currently, in our clinic, only patients with suspected Pendred-syndrome, representing the most frequent syndrome with hearing impairment, undergo a routine search for mutation detection in the corresponding gene SLC26A4. A multitude of genes and mutations are seen in the non-syndromic forms of hereditary hearing impairment. The gene gap-junction-protein beta2, encoding connexin 26, is encountered most frequently. Its prevalence in Switzerland is high with about 20% in the non-syndromic group. A molecular-genetic analysis of connexin 26 is offered in cases of congenital hearing loss. Another analysis, which has been implemented in the clinic, is the sequencing of Wolfram-syndrome gene 1 in familial low-frequency hearing loss. This gene seems to be involved in the majority of families with this type of hearing loss. Gene therapy for hearing loss is currently not an option in the clinical field. The different steps in carcinogenesis of head and neck cancer have further been elucidated by molecular-genetic research. Clinical applications are the establishment of risk-profiles for tumor-development and defining prognostic markers as well as the development of new treatment strategies based on genetic therapy.

Pulmonary atresia with ventricular septal defect and persistent airway hyperresponsiveness

Objective: We and others have observed significant hyperinflation and airflow obstruction after the surgical repair of pulmonary atresia and ventricular septal defect. This study sought to objectively characterize this problem and determine the prevalence of airway hyperresponsiveness in these patients. Methods: We performed a prospective study of children and young adults with pulmonary atresia and ventricular septal defect between June 1996 and December 1998. The participants were stratified into 2 distinct molecular genotypes on the basis of chromosome 22q11.2 microdeletion. A clinical diagnosis of asthma and an objective assessment of airway hyperresponsiveness were determined by means of an asthma inventory scale and methacholine challenge testing, respectively. Thirty-three patients were enrolled. Thirteen had velocardiofacial syndrome, each with chromosome 22q11.2 microdeletion. Results: None of the nonsyndromic patients had evidence for haploinsufficiency. Overall, 66.7% (22/33) met criteria for a clinical diagnosis of airway hyperresponsiveness: 62% (8/13) from the microdeletion genotype and 70% (14/20) from the nonsyndromic group. Conclusions: We have identified an extremely strong association between pulmonary atresia and ventricular septal defect and persistent airway hyperresponsiveness. Haploinsufficiency at chromosome 22q11.2 did not contribute to this predilection for airway hyperresponsiveness. These results provide a basis to anticipate persistent respiratory difficulties after operations in patients with pulmonary atresia and ventricular septal defect. Moreover, this at-risk patient population may yield unique insights into fundamental mechanisms involved in the pathogenesis of airway hyperresponsiveness.J Thorac Cardiovasc Surg 2001;122:169-77

A genetic aetiological survey of severe childhood deafness in the United Arab Emirates.

The aim of this study was to provide a genetic aetiological survey of children attending classes for the deaf in the United Arab Emirates (UAE) in whom a known acquired cause for their deafness had been excluded. Four schools in four different Emirates participated in the study (Sharjha, Khor Fakan, Dubai and Al-Ain). In each child a detailed history was obtained. This included a detailed family history, the level of consanguinity between the parents, ethnic origin, and the age of onset and progression of the deafness. The deafness was classified into syndromic and non-syndromic groups. These were then subdivided into autosomal recessive (AR), autosomal dominant (AD), X-linked recessive (XR), and sporadic. A total of 74 children from 51 families were included in the study. Fourteen of these (19 per cent) had syndromic deafness and 60 (81 per cent) had non-syndromic deafness. Overall there was a high prevalence of AR deafness (92 per cent) with AD deafness constituting 7 per cent and sporadic deafness 1 per cent, and no X-linked cases. In the syndromic group AR syndromes comprised 57 per cent of cases, AD 43 per cent, with no X-linked or sporadic cases. In the non-syndromic group almost all cases were AR (98 per cent), with no AD or X-linked cases, and one sporadic case. The level of consanguinity in the study group was 74 per cent with a high number of complexly consanguineous families (34 per cent). Eighty-six per cent of the children had a positive family history, 54 per cent of those had affected siblings, 50 per cent of which had more than one affected sibling. However, almost all the parents were not aware that the deafness in their children was genetic in origin.

Case report: paucity of interlobular bile ducts in Chinese children.

Sixteen Chinese children with cholestasis since early infancy were diagnosed to have paucity of interlobular bile ducts (PILBD) or its equivalent. Twelve children belonged to the syndromic group of PILBD and four children belonged to the non-syndromic group. A definite histological diagnosis of bile duct paucity was established in only two children (aged 4 and 9 months) during the first percutaneous needle biopsy. In the remaining 14 children a varying degree of bile duct destruction was evident in the follow up percutaneous or wedge liver biopsies. The evolving changes were characterized by inflammatory infiltration near or at the ductal wall, the presence of dysmorphic ductules, the degeneration of ductal epithelia and a progressive decrease of interlobular bile ducts. Of 10 children who underwent laparotomy for definite diagnosis, kasai operation was performed in two of them. In the syndromic PILBD group, all children, including two paired siblings, had at least three of five major clinical features. Hypoplasia of the extrahepatic biliary tree was found in five children and atresia of the extrahepatic bile duct was found in one. Three of six children studied were shown, by polymerase chain reaction, to have cytomegalovirus infection in the liver. This study demonstrates that bile duct paucity is a result of progressive bile duct destruction. A definitive diagnosis is difficult to make in early infancy. Thus, the careful evaluation of extrahepatic features in cholestatic children and follow-up liver biopsies are indicated. Although the pathogenetic mechanism of PILBD is unknown, bile duct destruction is the common pathway leading to paucity of bile ducts irrespective of syndromic or non-syndromic types.