First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations
Por:
Roman Corona-Rivera, Jorge, Carlos Zenteno, Juan, Gildardo Lopez-Perez, Leopoldo, Yokoyama-Rebollar, Emiy, Villarroel, Camilo E., Barragan-Arevalo, Tania, Angel Montes-Almanza, Luis, Consuelo Zepeda-Romero, Luz, Elena Morales-Dominguez, Guadalupe, Pena-Padilla, Christian, Bobadilla-Morales, Lucina, Corona-Rivera, Alfredo
Publicada:
1 abr 2023
Ahead of Print:
1 dic 2022
Resumen:
Introduction: 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. Case Presentation: 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. Discussion: 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.
Filiaciones:
Roman Corona-Rivera, Jorge:
Dr Juan I Menchaca Civil Hosp Guadalajara, Pediat Div, Serv Genet & Cytogenet Unit, Ctr Registry & Res Congenital Anomalies CRIAC, Guadalajara, Jalisco, Mexico
Univ Guadalajara, Hlth Sci Univ Ctr, Dr Enrique Corona Rivera Inst Human Genet, Dept Mol Biol & Genom, Guadalajara, Jalisco, Mexico
Carlos Zenteno, Juan:
Inst Ophthalmol Conde Valenciana, Dept Genet, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Dept Biochem, Fac Med, Mexico City, DF, Mexico
Gildardo Lopez-Perez, Leopoldo:
UMAE, Mexican Social Secur Inst IMSS, Western Natl Med Ctr, Serv Genet,Hosp Pediat, Guadalajara, Jalisco, Mexico
Yokoyama-Rebollar, Emiy:
Natl Inst Pediat, Human Genet Dept, Mexico City, DF, Mexico
Villarroel, Camilo E.:
Natl Inst Pediat, Human Genet Dept, Mexico City, DF, Mexico
Barragan-Arevalo, Tania:
Inst Ophthalmol Conde Valenciana, Dept Genet, Mexico City, DF, Mexico
Angel Montes-Almanza, Luis:
Inst Ophthalmol Conde Valenciana, Dept Genet, Mexico City, DF, Mexico
Consuelo Zepeda-Romero, Luz:
Fray Antonio Alcalde Civil Hosp Guadalajara, Div Pediat, Serv Ophthalmol, Guadalajara, Jalisco, Mexico
Elena Morales-Dominguez, Guadalupe:
Dr Juan I Menchaca Civil Hosp Guadalajara, Pediat Div, Serv Genet & Cytogenet Unit, Ctr Registry & Res Congenital Anomalies CRIAC, Guadalajara, Jalisco, Mexico
Pena-Padilla, Christian:
Dr Juan I Menchaca Civil Hosp Guadalajara, Pediat Div, Serv Genet & Cytogenet Unit, Ctr Registry & Res Congenital Anomalies CRIAC, Guadalajara, Jalisco, Mexico
Bobadilla-Morales, Lucina:
Dr Juan I Menchaca Civil Hosp Guadalajara, Pediat Div, Serv Genet & Cytogenet Unit, Ctr Registry & Res Congenital Anomalies CRIAC, Guadalajara, Jalisco, Mexico
Univ Guadalajara, Hlth Sci Univ Ctr, Dr Enrique Corona Rivera Inst Human Genet, Dept Mol Biol & Genom, Guadalajara, Jalisco, Mexico
Corona-Rivera, Alfredo:
Dr Juan I Menchaca Civil Hosp Guadalajara, Pediat Div, Serv Genet & Cytogenet Unit, Ctr Registry & Res Congenital Anomalies CRIAC, Guadalajara, Jalisco, Mexico
Univ Guadalajara, Hlth Sci Univ Ctr, Dr Enrique Corona Rivera Inst Human Genet, Dept Mol Biol & Genom, Guadalajara, Jalisco, Mexico
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