Characteristic Face: A Key Indicator for Direct Diagnosis of 22q11.2 Deletions in Chinese Velocardiofacial Syndrome Patients

Abstract

Velocardiofacial syndrome (VCFS) is a disease in human with an expansive phenotypic spectrum and diverse genetic mechanisms mainly associated with copy number variations (CNVs) on 22q11.2 or other chromosomes. However, the correlations between CNVs and phenotypes remain ambiguous. This study aims to analyze the types and sizes of CNVs in VCFS patients, to define whether correlations exist between CNVs and clinical manifestations in Chinese VCFS patients. In total, 55 clinically suspected Chinese VCFS patients and 100 normal controls were detected by multiplex ligation-dependent probe amplification (MLPA). The data from MLPA and all the detailed clinical features of the objects were documented and analyzed. A total of 44 patients (80.0%) were diagnosed with CNVs on 22q11.2. Among them, 43 (78.2%) presented with 22q11.2 heterozygous deletions, of whom 40 (93.0%) had typical 3-Mb deletion, and 3 (7.0%) exhibited proximal 1.5-Mb deletion; no patient was found with atypical deletion on 22q11.2. One patient (1.8%) presented with a 3-Mb duplication mapping to the typical 3-Mb region on 22q11.2, while none of the chromosomal abnormalities in the MLPA kit were found in the other 11 patients and 100 normal controls. All the 43 patients with 22q11.2 deletions displayed characteristic face and palatal anomalies; 37 of them (86.0%) had cognitive or behavioral disorders, and 23 (53.5%) suffered from immune deficiencies; 10 patients (23.3%) manifested congenital heart diseases. Interestingly, all patients with the characteristic face had 22q11.2 heterozygous deletions, but no difference in phenotypic spectrum was observed between 3-Mb and 1.5-Mb deletions. Our data suggest that the characteristic face can be used as a key indicator for direct diagnosis of 22q11.2 deletions in Chinese VCFS patients.

22q11.2 deletion syndrome in diverse populations

“…Repetto et al (); Grassi et al (); Matsuoka et al (); Wu et al (); Liu et al (); Veerapandiyan et al (); McDonald‐McGinn et al ().…”

“…Liu et al () found that in every 10 adult patients with conotruncal anomalies, 1 previously unrecognized diagnosis of 22q11.2 DS was present. Another group studying Chinese individuals found that all 43 of their study participants with 22q11.2 DS had typical facial findings consisting of a vertically long face, narrow palpebral fissures, fleshy nose with a broad nasal root, flattened malar region, retrognathia, and overfolded helix; however, this was not a prospective study and it is difficult to determine if these findings would have been made without knowing the molecular diagnosis (Wu et al, ). Clinical descriptions of Latin Americans is scarce; one large study of 208 patients described multi‐systemic anomalies in a Chilean population but did not include facial features (Repetto et al, ).…”

Microdeletion and Microduplication Analysis of Chinese Conotruncal Defects Patients with Targeted Array Comparative Genomic Hybridization

“…For the deletions and duplications detected with targeted aCGH, we confirmed the breakpoints by hybridizing the DNA of the affected individuals, including 10 cases of VCFS and 2 cases of cri du chat syndrome which were diagnosised by clinical features, imageological examination or surgery and confirmed by MLPA [19]. …”

Orthopedic and orthodontic management in a patient with DiGeorge Syndrome and Familial Mediterranean Fever: A case report

“…These patients have a characteristic facies with microcephaly, thick hair, rounded forehead/frontal lumps, flat profile, malar hypoplasia, narrow and/or antimongoloid palpebral fissures, hypertelorism, epicanthus, prominent nose with squared‐off nasal tip, low nasal bridge, small mouth which is open at rest, short philtrum, small chin, micrognathia, ogival palate, and hypotonic face. The ears are low set, cup‐shaped with malformed auricles overfolded helix …”

“…The ears are low set, cup-shaped with malformed auricles overfolded helix. 11 Cephalometrically, the faces are long, both maxillae and mandibles are retrognathic, and the lower jaws are posteriorly divergated. 12,13 Oral findings include anomalies in dental enamel (enamel hypoplasia and opacity) and in tooth shape, 14,15 tooth agenesis, delayed dental development and tooth eruption in both the primary and permanent dentition.…”