Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene. (21st October 2022)

• Record Type: Journal Article
• Authors: Horton‐Bell, Megan; Hamilton, Sue; Keelagher, Rebecca; Allen, Stephanie; De Burca, Anna; Ioannou, Christos; Impey, Lawrence; Cilliers, Deirdre
• Is Part Of: Prenatal diagnosis. Volume 42:Number 12(2022)
• Page Start: 1481
• Page End: 1483
• Publication Date: 2022-10-21
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6249
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Aims: A couple were referred for prenatal genetic testing at 31 weeks' gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and a small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. Materials and Methods: Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid. Results: A pathogenic homozygous nonsense variant in KLHL7 (NM_001031710.2) associated with PERCHING syndrome (#617055) was identified. Conclusion: Whilst there are detailed descriptions of the many postnatal phenotypes seen in these patients, there are few reports of features identified during pregnancy. This report is the first published prenatal diagnosis of PERCHING syndrome and provides further information on the associated fetal phenotypes. Key points: What is already known about this topic? PERCHING syndrome is a rare multisystem disorder caused by biallelic pathogenic variants in KLHL7. Postnatal phenotypes are well characterised and include retinitis pigmentosa, respiratory distress and neurologic abnormalities. Intrauterine growth retardation and polyhydramnios have been reported, however information regarding prenatal manifestations is limited. What does this study add? This report extends the prenatal phenotype to include neurological abnormalities. To our knowledge, it is the first prenatally diagnosed case of PERCHING syndrome published in the literature.