American Journal of Medical Genetics Part A | 2019
In This Issue
Abstract
POSSIBLE NEW SYNDROME INVOLVING HPE IDENTIFIED Holoprosencephaly (HPE) is a common congenital anomaly of the developing forebrain in humans that affects both the brain and the face. Approximately 50–60% of HPE cases are due to chromosomal abnormalities and submicroscopic deletions and/or duplications. In addition, the phenotype is also related to environmental factors, including maternal diabetes. It may also be part of multiple malformation syndromes. Richieri-Costa et al (p. 2170, 10.1002/ ajmg.a.61305) report on a possible new syndrome that includes HPE. A Brazilian child presented with semilobar holoprosencephaly, frontonasal encephaloceles, and bilateral cleft lip and palate. He was the second child of a healthy 20-year-old woman (father unknown) who smoked during pregnancy. There was no known exposure to other teratogens, and the older sibling was healthy. Other malformations included agenesis of the corpus callosum, abnormal cortical gyres, dilation of the aqueduct, bilateral endolymphatic sac, bilateral cystic cocci-vestibular malformation, and a cribriform defect. Craniofacial images also revealed an abnormal frontonasal transition region, but the child’s trunk and upper and lower limbs were normal. The authors note that, to their knowledge, “this rare association of holoprosencephaly with frontonaso-orbital encephaloceles without limb anomalies has never been reported before.” While the karyotype was normal and SNP-array revealed no copy-number alterations, the authors found up to 25% of regions of homozygosity (ROH) had a normal copy number suggesting a high coeffi cient of inbreeding, and a possible autosomal recessive disorder. No pathogenic or likely pathogenic variants were identifi ed during whole-exome sequencing, although the authors investigated the possible influence of two variants of uncertain significance that were detected within the patient’s ROHs. They noted that, “Further studies and/or the identification of other patients with a similar phenotype will help elucidate the genetic etiology of this complex case.” ADVERSE EFFECTS OF ANTIPSYCHOTICS IN 22Q11.2 DELETION SYNDROME NEED FURTHER STUDY