Introduction
Kleefstra syndrome-1 is a rare genetic syndrome characterized by intellectual disability, hypotonia, microcephaly and a complex pattern of congenital anomalies including congenital heart disease, renal and genitourinary malformation. Kleefstra syndrome-1 is caused by a heterozygous deletion at chromosome 9q34.3 or a heterozygous intragenic EHMT1 pathogenic variant. On the other hand, Peters anomaly is a rare ophthalmic congenital disorder resulting from dysgenesis of the anterior segment. It is

characterized by corneal opacity. It can be associated systemic abnormalities like cleft lip, cleft palate, short stature, abnormal ears, and intellectual disability, collectively known as Peters plus syndrome. Ophthalmic manifestation in Kleefstra syndrome-1 is not well-described in the medical literature. In 2014, Matsumoto, et al. (2014) described abnormal eye movement including rotatory nystagmus as a manifestation of Kleefstra syndrome-1, caused by 9q33q34 microdeletion. We present the first patient with confirmed Kleefstra syndrome-1 who presented with Peters anomaly, syndactyly, and multiple congenital anomalies. 

 

Case Presentation
Our patient is a male presented prenatally with IUGR and congenital heart disease (coarctation of aorta and VSD) noted on fetal ultrasound. He was born at 29 weeks and 4 days. His birth weight was between the 3rd and 10th percentile, his birth length was at the 3rd percentile, while his head circumference was below the 3rd percentile. He was found to have bilateral corneal clouding and his ophthalmology evaluation was consistent with Peters anomaly. He was found to have syndactyly over his left hand between the first and the second fingers, and bilateral club feet. His echocardiogram showed transverse arch hypoplasia, bicuspid aortic valve, VSD, ASD, and PDA.



 

Diagnostic Workup
His 7-dehydrocholesterol level was normal. His SNP array identified a pathogenic 3.75 Mb deletion within chromosome 9q34.3 consistent with the diagnosis of 9q34.3 deletion syndrome or Kleefstra syndrome 1 (OMIM: 610253). 

Conclusion
Kleefstra syndrome-1 is rare multiple congenital anomalies syndrome and its phenotype is evolving. Kleefstra et al. (2009) reported 16 patients with 9q deletions with intellectual disability, hypotonia, characteristic facial features, and multiple congenital anomalies. Since then, multiple other patients have been described. In the medical literature, reported ophthalmic manifestation of Kleefstra syndrome-1 is limited to refractive errors and abnormal eye movements. Peters anomaly and syndactyly have not been previously reported in patients with Kleefstra syndrome-1. Our patient’s distinctive presentation with Peters anomaly and syndactyly represent a phenotypic expansion in Kleefstra syndrome-1. It highlights the importance of recognizing Kleefstra syndrome-1 as a possible cause of Peters anomaly and syndactyly and adds to the available medical literature.