Velo-cardio-facial syndrome: The pediatric otolaryngologist's perspective

Current Opinion in Otolaryngology and Head and Neck Surgery

Volumn 13, Issue 6, 2005, Pages 371-375

  Butts, Sydney C ^a,b   Tatum III, Sherard A ^a,b   Mortelliti, Anthony J ^a,b   Shprintzen, Robert J ^a,b  

^a State University of New York Upstate Medical University: College of Medicine   (United States)

^b SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

Author keywords

22q11 deletion syndrome; Congenital heart disease; DiGeorge sequence; Fluorescence in situ hybridization; Immune disorder; Pharyngeal flap; TBX1; Velo cardio facial syndrome; Velopharyngeal insufficiency

Indexed keywords

CHROMOSOME 22Q; CHROMOSOME DELETION; ENDOCRINE DISEASE; FAMILY; GENE; GENE DELETION; GENETIC ANALYSIS; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; IMMUNITY; MOLECULAR GENETICS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SURGICAL APPROACH; SURGICAL TECHNIQUE; TREATMENT OUTCOME; VELOCARDIOFACIAL SYNDROME;

AUTOIMMUNE DISEASES; CHROMOSOMES, HUMAN, PAIR 22; DIGEORGE SYNDROME; HUMANS; HYPOCALCEMIA; IN SITU HYBRIDIZATION, FLUORESCENCE; OTOLARYNGOLOGY; OTOLOGIC SURGICAL PROCEDURES; T-BOX DOMAIN PROTEINS;

EID: 27944437397     PISSN: 10689508     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.moo.0000186203.53214.ac     Document Type: Review

References (43)

1. Shprintzen RJ, Goldberg RB, Lewin ML, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J 1978; 15:56-62.
2. Robin NR, Shprintzen RJ. Defining the clinical spectrum of deletion 22q11.2. J Pediatr 2005; 147:90-96. This paper gives a review of the clinical features associated with the syndrome and a historical overview of initial descriptions of the disease as well as a discussion about how to place this ever-growing list of associated clinical features into the context of the syndrome while preventing unwarranted genetic testing.
3. Becker DB, Pilgram T, Marty-Grames L. Accuracy in identification of patients with 22q11.2 deletion by likely care providers using facial photographs. Plast Reconstr Surg 2004; 114:1367-1372. Surveys of clinicians who care for patients with 22q11 deletion were taken to measure their ability to diagnose the syndrome from frontal photographs alone. This paper emphasizes the need for more uniform referral criteria for genetic testing.
4. Oskarsdottir S, Persson C, Eriksson BO, Fasth A. Presenting phenotype in 100 children with the 22q11 deletion syndrome. Eur J Pediatr 2005; 164: 146-153. This paper correlates age at diagnosis with major phenotypic features and makes recommendations about referral for genetic testing based on age at presentation.
5. Tobias ES, Morrison N, Whitford ML, Tolmie JL. Towards earlier diagnosis of 22q11 deletions. Arch Dis Child 1999; 81:513-514.
6. McDonald-McGinn DM, Minugh-Purvis N, Kirschner RE, et al. The 22q11.2 deletion in African-American patients: an underdiagnosed population? Am J Med Genet 2005; 134A:242-246. This report considers reasons for the under-representation of African-Americans in the cohort of patients, focusing on the prevalence of facial dysmorphisms.
7. Miyamoto RC, Cotton RT, Rope AR, et al. Association of anterior glottic webs with velocardiofacial syndrome (chromosome 22q11.2 deletion). Otolaryngol Head Neck Surg 2004; 130:415-417. Patients with anterior glottic web were tested, and a high percentage were found to have 22q11 deletion. The implications for screening of this group of patients are considered.
8. Sullivan KE. The clinical immunological and molecular spectrum of chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Curr Opin Allergy Clin Immunol 2004; 4:505-512.
9. Ruiter EM, Bongers EMHF, Smeets EFCM, et al. No justification of routine screening for 22q11 deletions in patients with overt cleft palate. Clin Genet 2003; 64:216-219.
10. Oskarsdottir S, Vujic M, Fasth A. Incidence and prevalence of the 22q11 deletion syndrome: a population-based study in western Sweden. Arch Dis Child 2004; 89:148-151. This study estimated the incidence and prevalence rates of 22q11 deletion in a western region of Sweden. It underscores the importance of disease awareness and referring specialty in determining the age at diagnosis.
11. Rohrich RJ, Muzaffar AR. The African-American patient. In: Gunter JP, Rohrich RJ, Adams WP, editors. Dallas rhinoplasty: nasal surgery by the masters. 1st ed. St. Louis: Quality Medical Publishing; 2002. pp. 921-951.
12. McDonald-McGinn DM, Tonnesen MK, Laufer Cahna A, et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genet Med 2001; 3:23-29.
13. Antshel KM, Kates WR, Roizen N, et al. 22q11.2 deletion syndrome: genetics, neuroanatomy and cognitive/behavioral features. Neuropsychol Dev Cogn C Child Neuropsychol 2005; 11:5-19. This paper is a review of the genes that may be involved in the neuropsychiatric features of 22q11 deletion, the psychiatric phenotype, and anatomic changes in the brain that may underlie the phenotype.
14. Shooner KA, Rope AF, Hopkin RJ. Genetic analyses in two extended families with deletion 22q11 syndrome: importance of extracardiac manifestations. J Pediatr 2005; 146:382-387. This study focuses on clinical examinations of family members, showing the lack of significant cardiac disease to explain why many relatives remain without a diagnosis into adulthood.
15. Adeyinka A, Stockero K, Flynn H. Familial 22q11.2 deletions in DiGeorge/velocardiofacial syndrome are predominantly smaller than the commonly observed 3mb. Genet Med 2004; 6:517-520. This study documented the inheritance of the syndrome in several families in which cytogenetic data showed the frequency of smaller deletion sizes.
16. Fernandez L, Lapunzina P, Lopez Pajares I. Higher frequency of uncommon 1.5-2mb deletions found in familial cases of 22q11.2 deletion syndrome. am j med genet a 2005; 136:71-75. This report shows the prevalence of 1.5 MB deletions among five families it describes, as well as the frequency of maternal transmission.
17. Maalouf NM, Khashayar S, Odvina CV. A case of chromosome 22q11 deletion syndrome diagnosed in a 32-year-old man with hypoparathyroidism. J Clin Endocrinol Metab 2004; 89:4817-4820. This is a case report of patient who experienced symptomatic hypocalcemia as an adult, after which the diagnosis of 22q11 deletion was made.
18. Choi J-H, Shin Y-L, Kim G-H, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res 2005; 63:294-299. This paper reviews the pathophysiology of endocrine disease, emphasizing the importance of monitoring patients for hypocalcemia after the newborn period.
19. Weinzimer SA. Endocrine aspects of the 22q11.2 deletion syndrome. Genet Med 2001; 3:19-22.
20. Carel K, Gelfand EW. Late-onset intractable hypocalcemia in an adult with recently diagnosed 22q11.2 deletion syndrome. J Allergy Clin Immunol 2005; 115:S78. This is a case report of late-onset symptomatic hypocalcemia.
21. Brown JJ, Datta V, Browning MJ, Swift PGF. Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion. J Pediatr Endocrinol Metab 2004; 17:1575-1579. This article reviews the autoimmune diseases seen in 22q11 deletion, which are often organ specific. Several reports of Graves's disease are reviewed, and a case report of a 3-year-old boy is detailed.
22. Sediva A, Bartunkova J, Zachova R, et al. Early development of immunity in DiGeorge syndrome. Med Sci Monit 2005; 11:182-187. This study tracks the cellular immune function in children, showing the improvement in T cell parameters with age which normalize after age 2.
23. Rice HE, Skinner MA, Mahaffey SM, et al. Thymic transplantation for complete DiGeorge syndrome: medical and surgical considerations. J Pediatr Surg 2004; 39:1607-1615. Only rarely do patients have severe immunodeficiency. Thymus transplantation is now an option to reconstitute T cell function in the neonatal period.
24. Moylett EH, Wasan AN, Noroski LM, Shearer WT. Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. Clin Immunol 2004; 112:106-112. This retrospective review shows the excellent safety profile of live viral vaccines in patients who have adequate T cell numbers and function.
25. Stapel L, Andrews T, McDonald-McGinn D, et al. Allergies in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) and patients with chronic granulomatous disease. Pediatr Allergy Immunol 2005; 16:226-230. Atopy may be a clinical feature of 22q11 deletion. Patients were surveyed for symptoms, and eczema and wheezing were found most frequently.
26. Azzari C, Gambineri E, Resti M, et al. Safety and immunogenicity of measlesmumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome). Vaccine 2005; 23:1668-1671. The authors reviewed the safety of measles-mumps-rubella vaccine and found equal rates of seroconversion compared with control individuals, and few side effects.
27. Sullivan KE. Live viral vaccines in patients with DiGeorge syndrome. Clin Immunol 2004; 113:3.
28. Baldini A. Dissecting contiguous gene defects: TBX1. Curr Opin Genet Dev 2005; 15:279-284.
29. Kelly RG, Jerome-Majewska LA, Papaioannou VE. The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Hum Mol Genet 2004; 13:2829-2840. This paper shows the importance of TBX1 in the initiation of myogenesis in the branchial arches.
30. Liao J, Kochilas L, Nowotschin S, et al. Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. Hum Mol Genet 2004; 13:1577-1585. Using a mouse model, this group demonstrated a phenotype with many of the features of 22q11 deletion when one copy of the gene TBX1 was deleted, adding to the evidence that this is one the key genes underlying the syndrome.
31. Devriendt K, Schatteman I, Lemmerlin M, Dhooge I. Middle and inner ear malformations in velocardiofacial syndrome. Am J Med Genet 2004;131A:225-226. Two patients with congenital ossicular and otic capsule anomalies are described.
32. Mehendale FV, Birch MJ, Birkett L, et al. Surgical management of velopharyngeal incompetence in velocardiofacial syndrome. Cleft Palate Craniofac J 2004; 41:124-135. This paper outlines an algorithm for the surgical management of VPI in patients with 22q11 deletion and the role of staging of procedures. Pharyngeal flaps are not routinely used.
33. Zim S, Schelper R, Kellman R, et al. Thickness and histologic and histochemical properties of the superior pharyngeal constrictor muscle in velocardiofacial syndrome. Arch Facial Plast Surg 2003; 5:503-510.
34. Perkins JA, Lewis CW, Gruss JS, et al. Furlow palatoplasty for management of velopharyngeal insufficiency: a prospective study of 148 consecutive patients. Plast Reconstr Surg 2005; 116:72-80. This prospective study examined the treatment of VPI with Furlow palatoplasty. Patients were selected who had anterior displacement of the levator sling. Patients with 22q11 deletion have high rates of persistent VPI when Furlow palatoplasty is used, compared with their nonsyndromic counterparts.
35. Tatum SA, Chang J, Natalie H, Shprintzen RJ. Pharyngeal flap and the internal carotid in velocardiofacial syndrome. Arch Facial Plast Surg 2002; 4:73-80.
36. Husein M, Chang E, Cable B, et al. Outcomes for children with submucous cleft palate and velopharyngeal insufficiency. J Otolaryngol 2004; 33:222-226.
37. Hill VE, Pietucha S, Ells A. Congenital vascular tortuosity in DiGeorge syndrome mimicking significant retinopathy of prematurity. Arch Ophthalmol 2004; 122:132-133.
38. Mansour AM, Bitar FF, Traboulsi E, et al. Ocular pathology in congenital heart disease. Eye 2005; 19:29-34. This report stresses the importance of ophthalmologic evaluation in patients with congenital heart disease. A significant percentage of the syndromic patients in this group had 22q11 deletion.
39. Oberoi S, Vargervik K. Velocardiofacial syndrome with single central incisor. Am J Med Genet 2005;132A:194-197.
40. McDonald-McGinn D, Gripp K, Kirschner R, et al. Craniosynostosis: another feature of the 22q11.2 deletion syndrome. Am J Med Genet 2005; 136:358-362.
41. Ricchetti ET, States L, Hosalkar HS, et al. Radiographic study of the upper cervical spine in the 22q11.2 deletion syndrome. J Bone Joint Surg Am 2004; 86A:1751-1760. This report documents the frequency of certain high cervical vertebral anomalies. All symptomatic patients were at least 15 years old, which suggests that patients need long-term follow-up.
42. Saunders NC, Hartley BEJ, Sell D, Sommerlad B. Velopharyngeal insufficiency following adenoidectomy. Clin Otolaryngol 2004; 29:686-688. The authors compared the causes of postadenoidectomy VPI in a current survey with those in [43] to determine how changes in awareness of this postsurgical complication have affected its incidence.
43. Croft CB, Shprintzen RJ, Ruben RJ. Hypernasal speech following adenotonsillectomy. Otolaryngol Head Neck Surg 1981; 89:179-188.