title: Absent or hypoplastic thymus on ultrasound: a marker for deletion 22q11.2 in fetal cardiac defects.
abstract: OBJECTIVE
  Congenital heart defects (CHD), particularly conotruncal anomalies, may be associated with deletion of chromosome 22q11.2. Thymic aplasia or hypoplasia is known to be a typical feature in this condition. We aimed to establish (i) the prevalence of del22q11.2 in fetal CHD and (ii) whether ultrasound assessment of an absent or hypoplastic fetal thymus helps in preselection of a group who are at high risk for this deletion.
  
  
  METHODS
  In fetuses (> 16 weeks) with CHD, karyotyping and fluorescence in situ hybridization for 22q11.2 were offered and the fetal thymus was evaluated sonographically.
  
  
  RESULTS
  One hundred and forty-nine fetuses with CHD and normal karyotype were analyzed. Seventy-six fetuses had conotruncal anomalies. 22q11.2 deletion was present in 10 cases (6.7%), all of which had conotruncal anomalies (13.1%). Thymic hypoplasia or absence was suspected in 11 cases with conotruncal anomaly. Nine of these 11 had the deletion; two cases were false positive. One fetus with a normal-sized thymus had deletion of 22q11.2 (sensitivity 90%, specificity 98.5%, positive predictive value 81.8%, and negative predictive value 99.2%). By subtype of cardiac anomaly, there was deletion in four of six fetuses with interruption of the aortic arch, two of four with absent pulmonary valve syndrome, three of nine with truncus arteriosus and one of 11 cases of tetralogy of Fallot. Pulmonary atresia with ventricular septal defect (n = 7), right-sided aortic arch (n = 4), transposition of the great arteries (n = 14), double outlet right ventricle (n = 13) and other complex malpositions of the great vessels (n = 8) were not associated with the deletion.
  
  
  CONCLUSIONS
  Thymic hypoplasia or aplasia may reliably be diagnosed during fetal echocardiography. The technique allows identification of a group at high risk for 22q11.2 deletion and is more specific and sensitive than by subtype of cardiac anomaly alone.
authors.affiliation: Department of OBstetrics and Gynecology, Unit of Prenatal Diagnosis and Therapy, Charité Hospital CCM, Humboldt University, Berlin, Germany. rabih.chaoui@charite.de
authors.forename: R
authors.initials: R
authors.lastname: Chaoui
authors.forename: K D
authors.initials: KD
authors.lastname: Kalache
authors.forename: K S
authors.initials: KS
authors.lastname: Heling
authors.forename: C
authors.initials: C
authors.lastname: Tennstedt
authors.forename: C
authors.initials: C
authors.lastname: Bommer
authors.forename: H
authors.initials: H
authors.lastname: Körner
mesh_terms: D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging* / Q000235:genetics; D006801:Humans; D008206:Lymphatic Diseases / Q000151:congenital / Q000000981:diagnostic imaging* / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D013950:Thymus Gland / Q000002:abnormalities / Q000000981:diagnostic imaging*; D016216:Ultrasonography, Prenatal / Q000379:methods*
chemical_list: D005819:Genetic Markers