Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

Table 1

Clinical features and laboratory findings of the present cases. Cases 1 and 2 were diagnosed as definite and probable/possible CHARGE syndrome, respectively. Cardiovascular malformations frequently associated with 22q11.2 deletion syndrome and characteristics originally described as DiGeorge anomaly [2] were also found in both cases, but fluorescence in situ hybridization analysis did not demonstrate chromosomal microdeletion at 22q11.2. See the text for details of cardiovascular malformations. Clinical diagnosis of CHARGE syndrome was based on Blake’s criteria [8]. N/e, not examined.

Features/findings	Case 1	Case 2	Frequency in CHARGE syndrome [1, 8]	Frequency in 22q11.2 deletion syndrome [2, 3]
Major diagnostic characteristics for CHARGE syndrome
Ocular coloboma	Yes	No	80–90%
Choanal atresia or stenosis	Yes	No	50–60%
Cranial nerve dysfunction or anomaly
I: hyposmia or anosmia	N/e	N/e	70–90%
VII: facial palsy	No	No
VIII: auditory nerve hypoplasia	Yes	Yes
IX/X: swallowing problems	Yes	Yes
Characteristic CHARGE syndrome ear	Yes	Yes	90%
Minor diagnostic characteristics for CHARGE syndrome
Genital hypoplasia (micropenis, cryptorchidism)	No	Yes	70–80%
Developmental delay (delayed milestone, hypotonia)	Yes	Yes	100%	75%
Cardiovascular malformation	Yes	Yes	75–85%	49–83%
Growth deficiency	Yes	Yes	70%	4%
Orofacial cleft	No	No	15–20%	9–11%
Tracheoesophageal fistula	No	No	15–20%
Distinctive face	Yes	Yes	70–80%
Others
Immune deficiency/thymic deficiency	Yes	Yes	Rare	Most
Hypoparathyroidism/hypocalcemia	Yes	Yes	Rare	17–60%
Hypothyroidism	No	Yes
Hand anomalies	Yes	Yes	50%
CHD7 gene mutation	Yes	N/e	67%
Chromosome 22q11.2 deletion	No	No		96%
Diagnostic criteria for CHARGE syndrome [8]	4 major + 4 minor	2 major + 5 minor
	Definite	Probable/possible
Characteristics originally described as DiGeorge anomaly [2]	Yes	Yes