Robert Shprintzen, Ph.D. A founding member of the Velo-Cardio-Facial Syndrome Educational Foundation, Inc. and its first Executive Director, Dr. Shprintzen is Director of several programs at the State University of New York Upstate Medical University in Syracuse, New York, including the Communication Disorder Unit, the Velo-Cardio-Facial Syndrome International Center, and the Center for Genetic Communicative Disorders. He is Professor of Otolaryngology and Professor of Pediatrics at Upstate. Widely published and recognized internationally, he is credited for delineating four genetic disorders, including velo-cardio-facial syndrome (also known as Shprintzen syndrome), Shprintzen-Goldberg craniosynostosis syndrome, Shprintzen-Goldberg omphalocele syndrome, and Goldberg-Shprintzen syndrome. Karen Golding-Kushner, Ph.D. Karen J. Golding-Kushner, Ph.D., Executive Director of The Velo-Cardio-Facial Syndrome Educational Foundation, Inc.

• Preface Chapter 1: The History of VCFS The History of VCFS Two Major Events in 1992 Communication Disorders and VCFS The Significance of Two Anomalies Occurring Together The Implications for Speech Pathologists, Surgeons, and Other Craniofacial Specialties What Do I Call It? Chapter 2: The Expansive Phenotype of VCFS Craniofacial Anomalies Ear and Hearing Anomalies The Nose Eye Findings Cardiac Findings Vascular Anomalies Brain and Central Nervous System Anomalies Pharyngeal, Laryngeal, and Airway Anomalies Abdominal and Visceral Anomalies Limb Anomalies Problems in Infancy Genitourinary Anomalies Skeletal, Muscle, Spine, and Orthopedic Anomalies Skin and Hair Findings Endocrine and Immune Findings Speech and Language Disorders Cognitive, Learning, and Attentional Disorders Psychiatric Disorders Miscellaneous Anomalies Secondary Developmental Sequences Why the Expansive Phenotype ? Chapter 3: The Genetics of VCFS What Does Genetic Mean? Mode of Inheritance Describing the Genome at 22q11.2 Determining the Nature of the Deletion in VCFS How the Deletion Occurs Identifying the Genes in the Deleted Region Determining What the Genes Do, Identifying Candidate Genes for Specific Phenotypes, and Identifying Polymorphisms Animal Models and Knockouts How Is a Deletion Different from Other Mutations? Genetic Effects Outside of the 22q11.2 Region That Contribute to the Phenotype Epigenetic Factors That Might Contribute to the Phenotypic Spectrum Genetic Counseling for VCFS Mosaicism and Germline Mosaicism Counseling for People with VCFS Chapter 4: Triage in VCFS: Utilizing the Natural History Audiology (Hearing Testing) Cardiology (Pediatric Cardiology) Cardiothoracic Surgery Clinical Genetics and Genetic Counseling Dentistry and Orthodontics Developmental Pediatrics Endocrine Evaluation Gastroenterology (Pediatric Gastroenterology) Immunology Evaluation Magnetic Resonance Imaging and Angiography Nasopharyngoscopy, FEES or FEESST, Direct Laryngoscopy, Bronchoscopy, Esophagoscopy, and Gastroscopy Nephrology Neurology Neuropsychology Neurosurgical Evaluation Nutrition Ophthalmology (Pediatric Ophthalmology) Orthopedics Otolaryngology Physical Therapy Podiatry Psychiatry Pulmonology (Pediatric Pulmonology) Reconstructive Surgery Renal Ultrasound Speech-Language Evaluation Urology Videofluoroscopy for Speech Videofluoroscopy for Swallowing Chapter 5: Growth, Weight Gain, and Feeding Is Short Stature a Feature of VCFS? Significance of these Data and the Growth Curve Possible Flaws in the Data Implications Feeding Therapy Emesis and Spitting Up Through the Nose Feeding Time (Duration) Feeding Position Type of Bottle and Nipple Burping Identifying and Understanding the Factors Leading to Problems What If the Child Already Has a Tube? Appendix: Clinical Synopsis of VCFS Index

Robert Shprintzen, Ph.D. A founding member of the Velo-Cardio-Facial Syndrome Educational Foundation, Inc. and its first Executive Director, Dr. Shprintzen is Director of several programs at the State University of New York Upstate Medical University in Syracuse, New York, including the Communication Disorder Unit, the Velo-Cardio-Facial Syndrome International Center, and the Center for Genetic Communicative Disorders. He is Professor of Otolaryngology and Professor of Pediatrics at Upstate. Widely published and recognized internationally, he is credited for delineating four genetic disorders, including velo-cardio-facial syndrome (also known as Shprintzen syndrome), Shprintzen-Goldberg craniosynostosis syndrome, Shprintzen-Goldberg omphalocele syndrome, and Goldberg-Shprintzen syndrome. Karen Golding-Kushner, Ph.D. Karen J. Golding-Kushner, Ph.D., Executive Director of The Velo-Cardio-Facial Syndrome Educational Foundation, Inc.

• Preface Chapter 1: The History of VCFS The History of VCFS Two Major Events in 1992 Communication Disorders and VCFS The Significance of Two Anomalies Occurring Together The Implications for Speech Pathologists, Surgeons, and Other Craniofacial Specialties What Do I Call It? Chapter 2: The Expansive Phenotype of VCFS Craniofacial Anomalies Ear and Hearing Anomalies The Nose Eye Findings Cardiac Findings Vascular Anomalies Brain and Central Nervous System Anomalies Pharyngeal, Laryngeal, and Airway Anomalies Abdominal and Visceral Anomalies Limb Anomalies Problems in Infancy Genitourinary Anomalies Skeletal, Muscle, Spine, and Orthopedic Anomalies Skin and Hair Findings Endocrine and Immune Findings Speech and Language Disorders Cognitive, Learning, and Attentional Disorders Psychiatric Disorders Miscellaneous Anomalies Secondary Developmental Sequences Why the Expansive Phenotype ? Chapter 3: The Genetics of VCFS What Does Genetic Mean? Mode of Inheritance Describing the Genome at 22q11.2 Determining the Nature of the Deletion in VCFS How the Deletion Occurs Identifying the Genes in the Deleted Region Determining What the Genes Do, Identifying Candidate Genes for Specific Phenotypes, and Identifying Polymorphisms Animal Models and Knockouts How Is a Deletion Different from Other Mutations? Genetic Effects Outside of the 22q11.2 Region That Contribute to the Phenotype Epigenetic Factors That Might Contribute to the Phenotypic Spectrum Genetic Counseling for VCFS Mosaicism and Germline Mosaicism Counseling for People with VCFS Chapter 4: Triage in VCFS: Utilizing the Natural History Audiology (Hearing Testing) Cardiology (Pediatric Cardiology) Cardiothoracic Surgery Clinical Genetics and Genetic Counseling Dentistry and Orthodontics Developmental Pediatrics Endocrine Evaluation Gastroenterology (Pediatric Gastroenterology) Immunology Evaluation Magnetic Resonance Imaging and Angiography Nasopharyngoscopy, FEES or FEESST, Direct Laryngoscopy, Bronchoscopy, Esophagoscopy, and Gastroscopy Nephrology Neurology Neuropsychology Neurosurgical Evaluation Nutrition Ophthalmology (Pediatric Ophthalmology) Orthopedics Otolaryngology Physical Therapy Podiatry Psychiatry Pulmonology (Pediatric Pulmonology) Reconstructive Surgery Renal Ultrasound Speech-Language Evaluation Urology Videofluoroscopy for Speech Videofluoroscopy for Swallowing Chapter 5: Growth, Weight Gain, and Feeding Is Short Stature a Feature of VCFS? Significance of these Data and the Growth Curve Possible Flaws in the Data Implications Feeding Therapy Emesis and Spitting Up Through the Nose Feeding Time (Duration) Feeding Position Type of Bottle and Nipple Burping Identifying and Understanding the Factors Leading to Problems What If the Child Already Has a Tube? Appendix: Clinical Synopsis of VCFS Index