This article reports the present situation of Brazilian health care in genetics for Orofacial Cleft (OFC) and 22q11.2 Deletions Syndrome (22q11.2 DS) based on research conducted by Brazil's Craniofacial Project (BCFP). Established in 2003, BCFP is a voluntary and cooperative network aiming to investigate the health care of people with these diseases and other craniofacial anomalies. The initiatives and research results are presented in four sections: (a) a comprehensive report of the Brazilian public health system in craniofacial genetics; (b) multicentric studies developed on OFC and 22q11.2 DS; (c) education strategies focused on addressing these conditions for both population and health-care professionals; and (d) the nosology through

No abstract

Orofacial clefts (OC) are the most common birth defects in humans and approximately 30% of them form the group of syndromic orofacial clefts (SOCs). Microphthalmia/anophthalmia/coloboma spectrum (MAC) can be associated with OC, however the genetic etiologies of OC-MAC have been poorly characterized. This study describes genomic findings among individuals with OC-MAC recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole exome sequencing (WES) were performed in 17 individuals with OC-MAC. Genotype-phenotype correlation was based on clinical data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them involving the CHD7 gene. Variant of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function. Investigation by WES seems to be the most effective method for diagnosis in OC-MAC. This study also reinforces the genetic heterogeneity of OC-MAC, highlights the presence of the CHD7 gene, and the importance of genes related to ciliopathies in this phenotype.

SATB2-associated syndrome (SAS) is a rare condition, and it is characterized by severe developmental delay/intellectual disability, especially severe speech delay/or absence, craniofacial abnormalities, and behavioral problems. Most of the published reports are limited to children, with little information about the natural history of the disease and the possible novel signs and symptoms or behavioral changes in adulthood. We describe the management and follow-up of a 25-year-old male with SAS due to a de novo heterozygous nonsense variant SATB2:c.715C>T:p.(Arg239*) identified by whole-exome sequencing and review the literature. The case herein described contributes to a better characterization of the natural history of this genetic condition and in addition to the genotype–phenotype correlation of the SATB2:c.715C>T:p.(Arg239*) variant in SAS, highlights some particularities of its management.