Medical Genetics in the Clinical Practice of ORL (Advances in Oto-Rhino-Laryngology, Vol. 70)

Experts in otorhinolaryngology as well as medical genetics have contributed their reviews to this comprehensive compilation. Introductory chapters deal with basic genetics followed by chapters devoted to specific disorders. The gamut of otorhinolaryngological diseases from both adult and pediatric practice is covered. Included are common disorders such as hearing loss, cleft lip and palate, and thyroid cancers as well as further chapters on rare disorders such as Usher syndrome, neurofibromatosis type 2 and paraganglioma. Also, emerging fields of genetic investigation including otitis media, chronic rhinosinusitis and gene therapy are discussed. The contributions focus on diagnosis and management, as well as practical issues like how to order genetic testing or refer to a medical geneticist or genetic counselor. This publication will serve as an educational and reference text for both adult and pediatric otorhinolaryngologists, as well as medical geneticists and genetic counselors. It will provide readers with an understanding of the current state of genetic disorders seen in ORL practice, allow for accurate diagnosis, and improve patient management. Medical Genetics in the Clinical Practice of ORL 2 Advances in Oto-Rhino-Laryngology 3 Contents 6 Preface 8 Genetic Basis of Conditions Commonly Seen inORL Practice 9 Abstract 9 Genetics of Hearing Impairment 12 Molecular Genetics in Head and Neck Cancer 14 Skull Base Tumors 16 Systemic Disease with OtolaryngologicFeatures 16 Conclusions 16 References 16 Basic Medical Genetics for the Otolaryngologist 18 Abstract 18 Basic Medical Genetics 18 Patterns of Inheritance 19 Genetic Phenomena that Impact Assessmentof Patterns of Inheritance 20 Obtaining a Family Medical History in theOtolaryngology Clinic 22 Resources 25 References 25 Ordering Genetic Tests and Interpreting the Results 26 Abstract 26 Choosing a Laboratory 26 Choosing the Right Test 27 Issues Related to Testing Minors 27 Informed Consent 28 GINA 29 What Genetic Tests Can Reveal AboutRelatives 29 What Positive and Negative Test Results Mean 30 Mutations, Polymorphisms, and Variants ofUnknown Significance 30 Evolving Knowledge and Technology and theImportance of Follow- Up 31 References 32 Referring Patients for a Medical GeneticsConsultation and Genetic Counseling 33 Abstract 33 Scope of Practice of Clinical Genetics 33 Qualifications and Training of a MedicalGeneticist 34 Qualifications and Training of a GeneticCounselor 34 When to Refer to a Medical Geneticist 34 When to Refer to a Genetic Counselor 34 Elements of a Genetic Evaluation 35 How to Find a Medical Geneticist 35 Reference 35 Towards an Etiologic Diagnosis: Assessing thePatient with Hearing Loss 36 Abstract 36 Universal Newborn Hearing Screening 37 Diagnosing the Etiology of Hearing Loss 37 Implications of Diagnosis 42 Conclusions 42 References 43 Nonsyndromic Hereditary Hearing Loss 45 Abstract 45 Autosomal Dominant NSHHL 46 Autosomal Recessive NSHHL 46 X- Linked NSHHL 47 Mitochondrial (Maternally Inherited) NSHHL 47 Importance of Genetics Consultation 48 Conclusions 48 Note 48 References 48 Hereditary Hearing Loss with ThyroidAbnormalities 51 Abstract 51 Resistance to Thyroid Hormone 51 Pendred Syndrome 52 Conclusion 55 References 55 Pigmentary Anomalies and Hearing Loss 58 Abstract 58 Hypopigmenation Syndromes 58 Hyperpigmentation Disorders 61 References 62 Usher Syndrome: Hearing Loss with Vision Loss 64 Abstract 64 Usher Syndrome 64 Clinical Evaluation of Hearing in USH Patients 65 Clinical Evaluation of Vestibular Function inUSH Patients 67 Clinical Evaluation of Retinal Function in USHPatients 68 Genetics of USH 68 Genotype- Phenotype Correlation for USHGenes 70 Why Are There No USH1 Mouse Models? 70 Acknowledgements 71 References 71 Genetic Disorders with both Hearing Loss andCardiovascular Abnormalities 74 Abstract 74 Defects of the Inner Ear Associated withCardiovascular Malformations 74 References 80 Hearing Loss Disorders Associated with RenalDisease 83 Abstract 83 Branchio- Oto- Renal Syndrome 83 Alport Syndrome 87 Miscellaneous Syndromes 88 Conclusion 89 References 89 Multiple Endocrine Neoplasia: Types 1 and 2 92 Abstract 92 Multiple Endocrine Neoplasia Type 1 92 Multiple Endocrine Neoplasia Type 2 95 Conclusions 97 Acknowledgements 97 References 97 Neurofibromatosis Type 2 99 Abstract 99 Epidemiology 99 Clinical Description 100 Genetics 101 Diagnosis 102 Differential Diagnosis 102 NF2 Management 103 Multidisciplinary Management 104 Conclusions 104 References 104 Hereditary Paragangliomas 107 Abstract 107 Herited Predisposition to Paragangliomas:Epidemiology and Risk Assessment 108 Prevalence and Clinical Manifestations of PGLSyndromes 108 Management of Patients with PGL 112 References 113 Genetic Causes of Nonsyndromic Cleft Lip with orwithout Cleft Palate 115 Abstract 115 Genetic Mapping of NSCLP Susceptibility Loci 116 Candidate Gene Screening 116 Conclusions 120 References 120 Chronic Rhinosinusitis 122 Abstract 122 Chronic Rhinosinusitis and Clinical Evaluations 122 Patients with Chronic Rhinosinusitis andSystemic Conditions 124 References 127 Otosclerosis 130 Abstract 130 Bone Remodeling and the Otic Capsule 131 Environmental Factors and Otosclerosis 131 Genetics of Otosclerosis 132 Family Linkage Studies 132 Candidate Gene Association Studies 133 Genome-Wide Association Study 134 Gene Expression in Otosclerosis 134 Concluding Remarks 135 References 135 Genetics of Vestibulopathies 138 Abstract 138 Benign Recurrent Vertigo 138 Bilateral Vestibulopathy 139 Meniere’s Disease 140 References 141 Genetics of Otitis Media 143 Abstract 143 Genetics of Otitis Media 143 Applying Genetics to Clinical Practice 147 References 148 Gene Therapy for Head and Neck Cancer 149 Abstract 149 Vectors 150 Gene Therapy Approaches 154 Conclusions 157 References 157 Author Index 160 Subject Index 161 Genetic basis of conditions commonly seen in ORL practice / Friedmann D.R., Lalwani A.K Basic medical genetics for the otolaryngologist / Alford, R.L., Darilek, S.A Ordering genetic tests and interpreting the results / Deignan, J.L., Grody, W.W. Referring patients for a medical genetics consultation and genetic counseling / Reid Sutton, V. Towards an etiologic diagnosis : assessing the patient with hearing loss / Lin, J., Oghalai, J.S. Nonsyndromic hereditary hearing loss / Alford, R.L. Hereditary hearing loss with thyroid abnormalities / Choi, B.Y. ... [et al.] Pigmentary anomalies and hearing loss / Toriello, H.V. Usher syndrome : hearing loss with vision loss / Friedman, T.B. ... [et al.] Genetic disorders with both hearing loss and cardiovascular abnormalities / Belmont, J.W. ... [et al.] Hearing loss disorders associated with renal disease / Kimberling, W.J., Borso, N., Smith, R.J. Multiple endocrine neoplasia : types 1 and 2 / Marsh, D.J., Gimm, O. Neurofibromatosis type 2 / Evans, D.G.R., Lloyd, S.K.W., Ramsden, R.T. Hereditary paragangliomas / Raygada, M., Pasini, B., Stratakis, C.A. Genetic causes of nonsyndromic cleft lip with or without cleft palate / Yuan, Q., Blanton, S.H., Hecht, J.T Chronic rhinosinusitis / Wang, X., Cutting, G.R. Otosclerosis / Ealy, M., Smith, R.J.H Genetics of vestibulopathies / Jen, J.C. Genetics of otitis media / Post, J.C. Gene therapy for head and neck cancer / Abuzeid, W.M., Li, D., O'Malley Jr., B.W.