22q11.2 deletion syndrome differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  : Ayushi Jain, M.B.B.S[2]

Overview

DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.

Differentiating [Disease name] from other Diseases

All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section. DGS must be differentiated from Smith-Lemli-Opitz syndrome, Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS), Alagille syndrome, VATER association, and CHARGE syndrome.

Differentiating DGS from other diseases on the basis of overlapping features

Differential Diagnosis			Clinical Manifestations Overlapping with DGS
Single Gene Disorders
Disorder	Gene Involved	Mode of Inheritance
Smith-Lemli-Opitz syndrome	DHCR7	AR	Polydactyly & cleft palate
Alagille syndrome	JAG1NOTCH2	AD	Butterfly vertebrae, CHD, & posterior embryotoxon
CHARGE syndrome	CHD7	AD	CHD, palatal anomalies, coloboma, choanal atresia, growth deficiency, ear anomalies / hearing loss, DDs, facial palsy, genitourinary anomalies, & immunodeficiency
Tetralogy of Fallot	TBX1 1	AD	CHD, preauricular pits
Chromosome Disorders	-	-
Deletion 10p13-p14		-	cardiac defects, immune deficiency, hypoparathyroidism, cleft palate, developmental delay, microcephaly, and cryptorchidism
Deletion 11q23-ter (Jacobsen syndrome)	-	-	microcephaly, micrognathia, low set ears, ocular manifestations, cardiac defects, hypospadias, cryptorchidism, and immune deficiency.
Other	-	-
Disorders of unknown genetic etiology	-	-
VACTERL association (when congenital heart disease, vertebral, renal, and limb anomalies are present)	-	-	VATER association is a diagnosis of exclusion without an established etiology to date
Oculoauriculovertebral (Goldenhar) syndrome (OAVS) (when ear anomalies, vertebral defects, heart disease, renal anomalies are present)	-	-	Ear anomalies, heart disease, Vertebral defects, renal anomalies.
Teratogenic exposures	-	-	A phenotype similar to 22q11.2DS can be associated with maternal diabetes and maternal retinoic acid exposure