Association Syndromes and Sequences Flashcards
(23 cards)
What anomalies are included in the CHARGE
association?
C Coloboma H Heart defect A Atresia, choanal R Retarded growth and development G Genital hypoplasia E Ear anomalies/hearing loss
What are poor prognostic factors in patients with
CHARGE association?
Midline malformations, esophageal atresia, and bilateral
choanal atresia
What head and neck anomalies are related to the
CHARGE association?
Choanal atresia, ear abnormalities and hearing loss, facial
nerve palsy, pharyngoesophageal dysmotility, laryngomala-
cia, vocal-cord paralysis or paresis, obstructive sleep apnea,
tracheoesophageal fistula, and gastroesophageal reflux.
Temporal bone abnormalities, such as hypoplasia of the
semicircular canals and Mondini malformation can also occur.
What gene is involved in the CHARGE association?
CHD7 gene (member of the chromodomain helicase DNA
protein family), chromosome 8q12 in 75% of patients with
CHARGE association
What is the incidence of choanal atresia in
patients with CHARGE association?
> 65%, > 2/3 bilateral. If unilateral, left > right
What does VACTERL association stand for?
V Vertebral defects
A Anal atresia
C Cardiac malformations
TE Tracheoesophageal fistula with esophageal atresia
R Renal dysplasia
L Limb anomalies (most commonly radial anomalies)
What percentage of patients with VACTERL
association have a tracheoesophageal fistula?
50 to 80%
What are the major clinical characteristics in
patients with velocardiofacial syndrome?
Clefting of the secondary palate, hypernasal speech, pha-
ryngeal hypotonia, structural heart anomalies, dysmorphic
facial appearance, slender hands and fingers, and learning
disabilities
What chromosomal anomaly is associated with
velocardiofacial syndrome?
About 80 to 100% have a hemizygous deletion of
chromosome 22q11.
What factors lead to velopharyngeal insufficiency
in patients with velocardiofacial syndrome?
Cleft palate (occult submucous cleft, overt submucous cleft
or soft palate cleft), hypotonia of the pharyngeal muscles,
platybasia (an obtuse angulation of the cranial base), and a
small adenoid pad
Why do most patients with velocardiofacial
syndrome have chronic otitis media and conductive
hearing loss despite having a small adenoid pad?
Abnormal craniofacial anatomy, cleft palate, and associated
eustachian tube dysfunction
What evaluation must be done when performing a
pharyngeal flap on a patient with velocardiofacial
syndrome? Why?
Nasopharyngoscopy (look for pulsations in the posterior or
lateral pharyngeal walls), computed tomography angiog-
raphy (CTA), or magnetic resonance angiography (MRA); 25
to 30% have medial displacement of their internal carotid
arteries.
What autosomal dominant syndrome is most
likely in a child with lower-lip pits, cleft lip,
and/or cleft palate?
Van der Woude syndrome
Describe lower-lip pits in van der Woude
syndrome.
Usually bilateral paramedian sinuses in the lower lips placed
symmetrically on either side of midline. They can also be
median, paramedian, or unilateral (usually left). A single
median or paramedian lower lip pit is considered an
incomplete expression of the trait.
Describe the embryologic formation of lower-lip
pits as seen in van der Woude syndrome.
The lower lip of a 32-day embryo consists of four growth
centers divided by one median and two lateral grooves. In
the 38-day embryo, the lateral grooves disappear unless
there is impeded mandibular growth, which results in the
formation of a lower lip pit.
What are the clinical features of Stickler syndrome?
Typical facial characteristics (micrognathia leading to Pierre
Robin sequence), hypermobility, and enlargement of joints
associated with the onset of arthritis in early adulthood,
myopia, retinal detachment, cataracts, and hearing loss
What is the genetic mutation in Stickler syndrome?
Mutations in the COL2A1, COL9A1, COL11A1, and COL11A2
genes cause Stickler syndrome. These genes are involved in
the production of type II, type IX, and type XI collagen,
which are components of vitreous, cartilage, and other
connective tissues.
What are the different types of Stickler syndrome,
and what are the associated genetic mutations?
● Type 1 (autosomal dominant) are mutations in the
COL2A1 gene and are the most common.
● Type 2 (autosomal dominant) are mutations in the
COL11A1 gene.
● Type 3 (autosomal dominant) are mutations in the
COL11A2 gene. No ocular abnormalities because COL11A2
is not present in the vitreous.
● Type 4 (autosomal recessive) are mutations in COL9A1.
What are the clinical findings in Pierre Robin
sequence?
Micrognathia, glossoptosis, and wide U-shaped cleft palate,
leading to upper airway obstruction and feeding difficulties
Describe the embryology of Pierre Robin
sequence.
Arrest in mandibular development at 7 to 11 weeks of
gestation (micrognathia) causes the tongue to set abnor-
mally high and posteriorly in the oral cavity (glossoptosis).
This prevents fusion of the palatal shelves at week 11 and
results in a U-shaped cleft palate.
What are the most common syndromes associated
with Pierre Robin sequence?
● Stickler syndrome (most common) ● Treacher Collins syndrome ● Velocardiofacial syndrome ● Fetal alcohol syndrome ● Möbius syndrome ● Nager syndrome ● Beckwith-Wiedemann syndrome
How often is Pierre Robin sequence associated
with a syndrome?
80% (20% isolated)
Discuss the treatment options for upper-airway
obstruction in patients with Pierre Robin sequence.
● 70%: Positioning alone (i.e., prone positioning)
● 20%: Nasopharyngeal airway, mandibular distraction
osteogenesis (gaining popularity), tongue-lip adhesion
(being performed less commonly)
● 10%: Tracheostomy
