Weill-Marchesani syndrome 4 caused by compound heterozygosity of a maternal submicroscopic deletion and a paternal nonsense variant in the gene: A case report.

PURPOSE

To retrospectively report a case of Weill-Marchesani syndrome 4 (WMS4) with compound heterozygous variants of gene.

OBSERVATIONS

The patient was a 7-year-old boy with progressively worsening eyesight and intermittent elevated intraocular pressure (IOP) for two years. His IOPs were temporarily controlled using anti-glaucoma drugs. At presentation he had a shallow anterior chamber, lens subluxation, spherophakia and extensive synechial angle closure with high myopia in both eyes. Ultrasound biomicroscopy (UBM) identified thickened zonule fibers and anteriorly rotated, flat and slender ciliary processes, both of which worsened and were accompanied by obvious iris bombe after miosis. Gene testing showed compound heterozygosity of a maternal submicroscopic deletion on chromosome 15q26.3 (0.774 Mb) affecting the sequences of , and as well as a paternal nonsense variant (c.1051_1053delAAGinsTAA, P.K351X) in the gene in the proband. The diagnosis of WMS4 was confirmed by genetic testing. Phacoemulsification (Phaco), intraocular lens (IOL) implantation, and irido-zonulo-hyaloid-vitrectomy (IZHV) combined with Ahmed Glaucoma Valve (AGV) implantation as a staged or one-stage surgery effectively lowered IOP, deepened ACD, improved visual acuity, and resolved the configuration of the ciliary processes in both eyes.

CONCLUSION AND IMPORTANCE

Recessive variants are associated with WMS4. We report here compound heterozygous variants in causing WMS4, and anatomically highlighted the possible pathophysiology for its clinical phenotype. A modified surgical approach with Phaco, IOL implantation, and IZHV combined with AGV implantation could be used to treat these complicated cases.