Emmie
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DiGeorge Syndrome
DiGeorge Syndrome
Emmie was born with a rare genetic disorder
which caused her heart/lung defect
and many other complications.
DiGeorge Syndrome has 185 anomolies associated with it ...
What is DiGeorge Syndrome?
DiGeorge syndrome is a rare congenital disease characterized a history of recurrent infection, heart defects and unique facial features.
What Causes DiGeorge Syndrome?
DiGeorge syndrome is caused by a large deletion from chromosome 22. The deletion is a result of an an error in recombination at meiosis. Several genes from chromosome 22 are not present in DiGeorge syndrome patients.
Symptoms of DiGeorge Syndrome?
The symptoms of DiGeorge syndrome vary greatly between individuals. Researches believe that the variation in the symptoms is related to the amount of genetic material lost in the chromosomal deletion. The more genetic material is lost, the greater the amount of symptoms.
Some common symptoms of DiGeorge syndrome are:
Speech impairments Immune deficiency Learning disabilities Hypocalcemia Recurrent infections Underdeveloped thymus gland Hypoparathyroidism Lack of T-cells 
Congenital heart disease Heart murmur Heart failure Underdeveloped parathyroid glands Underdeveloped chin Downward slanting eyes Convulsions Treatment Options for DiGeorge Syndrome?
The damaged chromosome cannot be repaired. Treatments are aimed to reduce symptoms and complications. Some common treatments are surgery for heart problems, and thymus cell transplants to restore the immune system.
DiGeorge Syndrome (aka VELO-CARDIO-FACIAL SYNDROME)
Velo-cardio-facial syndrome (VCFS) is caused by a deletion of a small
segment of the long arm of chromosome 22 known as Deletion 22q11. The
following list shows the anomalies that have been found in VCFS. No features
are found in 100% of cases, but all occur with sufficient frequency to warrant assessment.
Craniofacial/Oral Findings ****(Emmie has # 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, and 12)
.1. Overt, submucous or occult submucous cleft palate
.2. Retrognathia (retruded lower jaw)
.3. Platybasia (flat skull base)
.4. Asymmetric crying facies in infancy
.5. Structurally asymmetric face
.6. Functionally asymmetric face
.7. Vertical maxillary excess (long face)
.8. Straight facial profile
.9. Congenitally missing teeth (one or several)
.10. Small teeth
.11. Enamel hypoplasia (primary dentition)
.12. Hypotonic, flaccid facies
.13. Downturned oral commissures
.14. Cleft lip (uncommon)
.15. Microcephaly
.16. Small posterior cranial fossa
Eye Findings ****(Emmie has # 18, 29, and 31)
.17. Tortuous retinal vessels
.18. Suborbital congestion ("allergic shiners")
.19. Strabismus
.20. Narrow palpebral fissures
.21. Posterior embryotoxon
.22. Small optic disk
.23. Prominent corneal nerves
.24. Cataract
.25. Iris nodules
.26. Iris coloboma (uncommon)
.27. Retinal coloboma (uncommon)
.28. Small eyes
.29. Mild orbital hypertelorism
.30. Mild vertical orbital dystopia
.31. Puffy upper eyelids
Ear/Hearing Findings ****(Emmie has # 32 and 41)
.32. Overfolded helix
.33. Attached lobules
.34. Protuberant, cup-shaped ears
.35. Small ears
.36. Mildly asymmetric ears
.37. Frequent otitis media
.38. Mild conductive hearing loss
.39. Sensori-neural hearing loss (often unilateral)
.40. Ear tags or pits (uncommon)
.41. Narrow external ear canals
Nasal Findings **** (Emmie has # 43 and 46)
.42. Prominent nasal bridge
.43. Bulbous nasal tip
.44. Mildly separated nasal domes (nasal tip appears bifid)
.45. Pinched alar base, narrow nostrils
.46. Narrow nasal passages
Cardiac and Thoracic Vascular Findings ****(Emmie has # 47, 48, 49, 50 and 53)
.47. VSD (Ventricular septal defect)
.48. ASD (Atrial septal defect)
.49. Pulmonic atresia or stenosis
.50. Tetralogy of Fallot
.51. Right sided aorta
.52. Truncus arteriosus
.53. PDA (patent ductus arteriosus)
.54. Interrupted aorta, type B
.55. Coarctation of the aorta
.56. Aortic valve anomalies
.57. Aberrant subclavian arteries
.58. Vascular ring
.59. Anomalous origin of carotid artery
.60. Transposition of the great vessles
.61. Tricuspid atresia
Vascular Anomalies **** (Emmie has # 70)
.62. Medially displaced internal carotid arteries
.63. Tortuous or kinked internal carotids
.64. Jugular vein anomalies
.65. Absence of internal carotid artery (unilateral)
.66. Absence of vertebral artery (unilateral)
.67. Low bifurcation of common carotid
.68. Tortuous or kinked vertebral arteries
.69. Reynaud's phenomenon
.70. Small veins
.71. Circle of Willis anomalies
Neurologic, Brain, and MR Findings **** (Emmie has # 73, 74, 76, 77, 78, 79 and 81)
.72. Periventricular cysts (mostly at anterior horns)
.73. Small cerebellar vermis
.74. Cerebellar hypoplasia/dysgenesis
.75. White matter UBOs (unidentified bright objects)
.76. Generalized hypotonia
.77. Cerebellar ataxia
.78. Seizures
.79. Strokes
.80. Spina bifida occulta/meningomyelocele.
.81. Mild developmental delay
.82. Enlarged Sylvian fissure
Pharyngeal/Laryngeal/Airway Findings **** (Emmie has #84, 86, 87, 89, 93 and 94)
.83. Upper airway obstruction in infancy
.84. Absent or small a denoids
.85. Laryngeal web (anterior)
.86. Large pharyngeal airway
.87. Laryngomalacia
.88. Arytenoid hyperplasia
.89. Pharyngeal hypotonia
.90. Asymmetric pharyngeal movement
.91. Thin pharyngeal muscle
.92. Unilateral vocal cord paresis
.93. Reactive airway disease
.94. Asthma
Abdominal/Kidney/Gut **** (Emmie had # 99)
.95. Hypoplastic/aplastic kidney
.96. Cystic kidneys
.97. Inguinal hernias
.98. Umbilical Hernias
.99. Malrotation of bowel
.100. Diastasis recti
.101. Diaphragmatic hernia (uncommon)
.102. Hirschsprung megacolon (rare)
Limb Findings **** (Emmie has # 103,104 and 105)
.103. Small hands and feet
.104. Tapered digits
.105. Short nail beds
.106. Rough, red, scaly skin on hands and feet
.107. Morphea
.108. Contractures
.109. Triphalangeal thumbs
.110. Polydactyly, both pre- and postaxial (uncommon)
.111. Soft tissue syndactyly
Problems in Infancy **** (Emmie had/has all of these)
.112. Feeding difficulty, Failure-to-thrive
.113. Nasal vomiting
.114. Gastroesophageal reflux
.115. Irritability
.116. Chronic constipation (not Hirschsprung megacolon)
Genitourinary **** (Emmie has none of these)
.117. Hypospadias
.118. Cryptorchidism
.119. Vesico-ureteral reflux
Speech/Language **** (Emmie has all of these)
.120. Severe hypernasality
.121. Severe articulation impairment (glottal stops)
.122. Language impairment (usually mild delay)
.123. Velopharyngeal insufficiency (usually severe)
.124. High pitched voice
.125. Hoarseness
Cognitive/Learning **** (So far we know Emmie has 126 and 127)
.126. Learning disabilities (math concept, reading
comprehension)
.127. Concrete thinking, difficulty with abstraction
.128. Drop in IQ scores in school years (test artifact)
.129. Borderline normal intellect
.130. Occasional mild mental retardation
.131. Attention deficit hyperactivity disorder
Miscellaneous anomalies **** (Emmie has # 132, 133 and 135)
.132. Spontaneous oxygen desaturation without apnea
.133. Thrombocytopenia, Bernard-Soulier disease
.134. Juvenile rheumatoid arthritis
.135. Poor body temperature regulation
Psychiatric/Psychological **** (Emmie has # 144, 148 and 151)
136. Bipolar affective disorder
.137. Manic depressive illness and psychosis
.138. Rapid or ultrarapid cycling of mood disorder
.139. Mood disorder
.140. Depression
.141. Hypomania
.142. Schizoaffective disorder
.143. Schizophrenia
.144. Impulsiveness
.145. Flat affect
.146. Dysthymia
.147. Cyclothymia
.148. Social immaturity
.149. Obsessive compulsive disorder
.150. Generalized anxiety disorder
.151. Phobias
.152. Severe startle response
Immunologic **** (Emmie has all of these)
.153. Frequent upper respiratory infections
.154. Frequent lower airway disease (pneumonia,bronchitis)
.155. Reduced T cell populations
.156. Reduced thymic hormone
Endocrine**** (Emmie has # 157, 158, 160 and 161)
.157. Hypocalcemia
.158. Hypoparathyroidism
.159. Hypothyroidism
.160. Mild growth deficiency, relative small stature
.161. Absent, hypoplastic thymus
.162. Small pituitary gland (rare)
Skeletal/Muscle/Orthopedic **** (Emmie has # 163, 166, 168, 171, 172, 173, 174 and175)
.163. Scoliosis
.164. Spina bifida occulta
.165. Hemivertebrae
.166. Butterfly vertebrae
.167. Fused vertebrae (usually cervical)
.168. Osteopenia
.169. Sprengel's anomaly, scapular deformation
.170. Talipes equinovarus
.171. Small skeletal muscles
.172. Joint dislocations
.173. Chronic leg pains
.174. Flat foot arches
.175. Hyperextensible/lax joints
.176. Rib fusion
.177. Extra ribs
.178. Tethered cord
.179. Syrinx
Skin/Integument **** (Emmie has 180... and we LOVE it!)
.180. Abundant scalp hair
.181. Thin appearing skin (venous patterns easily visible)
Secondary Sequences/Associations
.182. Pierre Robin Sequence
.183. DiGeorge Sequence
.184. Potter Sequence
.185. CHARGE Association
.186. Holoprosencephaly
Some other facts about the syndrome:
Population prevalence (estimated): 1:2,000 people
Birth incidence (estimated): 1:1,800 births
Most common syndrome associated with cleft palate
Second most common syndrome associated with congenital heart disease
What is DiGeorge syndrome?
DiGeorge syndrome identified as a chromosomal microdeletion.
This syndrome is typified by conotruncal congenital heart disease, facial
abnormalities and endocrine and immune disorders.
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DiGeorge syndrome is characterized by a few specific cardiac malformations, a sub-set of facial attributes, and certain endocrine and immune anomalies.
The cause of DiGeorge syndrome has been identified as a submicroscopic deletion of chromosome 22 in the DiGeorge chromosomal region. It is classified along with velo-cardio-facial syndrome (Shprintzen syndrome) and conotruncal anomaly face syndrome as a 22q11 microdeletion and is sometimes referred to by the simple name 22q11 syndrome.
People with DiGeorge syndrome may have the following congenital heart lesions: tetralogy of Fallot, interrupted aortic arch type B, truncus arteriosus, aberrant left subclavian artery, right infundibular stenosis, or ventricular septal defect. 74% of patients with 22q11 syndrome have conotruncal malformations. 69% of patients are found to have palatal abnormalities including velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate.
Some of the facial characteristics of DiGeorge syndrome are bifid uvula, high-arched palate, small mouth and wide set eyes, down-slanting eyes, hooded eyes, long face, malar flatness, cupped low set ears, bulbous nasal tip, and a dimpled or bifurcated nasal tip. Not all people with a 22q11 microdeletion display all, or indeed, any, of these characteristics.
Immune deficiency of varying severity, hypocalcemia (which may lead to seizures) and hypoparathyroidism are some of the most prominent features of DiGeorge, (although not of Shprintzen syndrome which is characterized more by cleft palate and speech difficulties). The thymus gland and parathyroid glands are malformed and dysfunctional or missing altogether in a classic DiGeorge syndrome case.
Learning disorders and developmental delay effect 70% - 90% of individuals with DiGeorge syndrome.
The 22q11 microdeletion can be inherited and is found to be so in about 6% of cases. Parents with the 22q11 microdeletion have a 50% chance of passing the deletion to their offspring. 94% of DiGeorge cases are de novo deletions.
Alcohol consumption during the early stages of fetal development may be one of many environmental explanations for the microdeletion.
Prenatal testing for DiGeorge syndrome is widely available and is recommended for fetuses that have been detected as having cleft palate or heart malformation through ultrasound, and have at least one parent testing positive for the 22q11 microdeletion. Diagnosis at any stage of gestation is helpful in managing DiGeorge syndrome and planning for the care of the neonate.
Infants with the 22q11 microdeletion should be monitored for hypocalcemia, renal function and low lymphocyte count. Babies with low lymphocyte counts should be seen by an immunologist and should not be given live vaccine immunizations.
References
Human Genetics 90:663-5
American Journal of Human Genetics 50:924-33
Journal of Medical Genetics 30:813-7
Genetic Testing 1:99-108
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