{Reference Type}: Case Reports
{Title}: First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations.
{Author}: Corona-Rivera JR;Zenteno JC;López-Pérez LG;Yokoyama-Rebollar E;Villarroel CE;Barragán-Arévalo T;Montes-Almanza LÁ;Zepeda-Romero LC;Morales-Domínguez GE;Peña-Padilla C;Bobadilla-Morales L;Corona-Rivera A;
{Journal}: Mol Syndromol
{Volume}: 14
{Issue}: 2
{Year}: Apr 2023
{Factor}: 1.494
{DOI}: 10.1159/000526975
{Abstract}: <B>UNASSIGNED: </B>PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement.<BR><B>UNASSIGNED: </B>Here, we describe 4 individuals with PACS1-related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1-related NDD.<BR><B>UNASSIGNED: </B>We reviewed the ocular phenotypes reported in 74 individuals with PACS1-related NDD and the overlaps with WDR37- and PACS2-related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1-related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37-PACS1-PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes.