A Narrative Review of the Ocular Manifestations in Noonan Syndrome

Christou, Evita Evangelia; Zafeiropoulos, Paraskevas; Rallis, Dimitrios; Baltogianni, Maria; Asproudis, Christoforos; Stefaniotou, Maria; Giapros, Vasileios; Asproudis, Ioannis

doi:10.1080/08820538.2021.1955134

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…Abnormalities in ocular development and visual function are frequently detected in CFCS, similarly to other RASopathies, underlining the important role RAS pathway has on the visual system (Christou et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Systematic ophthalmologic evaluation in cardio‐facio‐cutaneous syndrome: A genotype–endophenotype correlation

Crincoli,

Leoni,

Viscogliosi

et al. 2023

American J of Med Genetics Pt A

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Cardio‐facio‐cutaneous syndrome (CFCS) is a rare genetic disorder belonging to the RASopathies, a group of developmental syndromes caused by upregulated RAS/MAPK signaling. Pathogenic variants affecting four genes, KRAS, BRAF, MAP2K1 and MAP2K2, encoding core signal transducers of the pathway, underlie the condition. Major clinical features include a distinctive facies, ectodermal and cardiac anomalies, reduced postnatal growth, intellectual disability, and musculoskeletal abnormalities. Similar to other RASopathies, reports of visual impairment, high refractive error, optic nerve pallor, and other ocular abnormalities have been anecdotally reported in the literature. The aim of our study is to report the prevalence of ophthalmologic abnormalities in a large monocentric cohort of individuals affected by CFCS and explore the occurrence of genotype–endophenotype correlations in this series of patients. We observed that BRAF mutations are associated to a higher prevalence of anisometropia >3D (11.8% vs. 0%) and high astigmatism (29.4% vs. 0%; both p < 0.001) while patients with mutations in other genes had a significantly higher prevalence of myopia >6 D (60% vs. 5.9%; p = 0.012). Pale optic disc was associated with higher prevalence of inferior oblique muscle (IO) overaction (33.3% vs. 0%) and lower prevalence of ptosis (0% vs. 11.8%; both p < 0.001). Combined exotropia, IO overaction and nystagmus were frequent in patients with pale optic nerve. Our findings might suggest the need for earlier ophthalmologic referral for CFCS patients due to high risk of amblyopia, especially those expressing BRAF mutations.

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Section: Discussionmentioning

confidence: 99%

Systematic ophthalmologic evaluation in cardio‐facio‐cutaneous syndrome: A genotype–endophenotype correlation

Crincoli,

Leoni,

Viscogliosi

et al. 2023

American J of Med Genetics Pt A

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“…The ophthalmologic findings of NS include a broad spectrum of mainfestations, such as external ocular malformations, refractive errors, mobility abnormalities, and ocular anterior and posterior segment disorders. One of the main criteria for the diagnosis of NS is facial dysmorphology with external ocular features, consisting of hypertelorism, epicanthic folds, ptosis, and/or down-slanting palpebral fissures ( 23 ). Marin et al ( 24 ) showed that the most common finding (74%) in patients with identified PTPN11 variants was down-slanting palpebral fissures.…”

Section: Discussionmentioning

confidence: 99%

“…Marin et al ( 24 ) showed that the most common finding (74%) in patients with identified PTPN11 variants was down-slanting palpebral fissures. Refractive errors (astigmatism-myopia-hyperopia) have also been reported to be common ocular findings ( 23 ). In patients with refractive errors, PTPN11 variant has usually been detected ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Variability in a Noonan Syndrome Family with a Homozygous PTPN11 Gene Variant in Two Individuals

Yıldırım,

Unal,

Özalkak

et al. 2023

Jcrpe

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Objective: Noonan syndrome (NS) is characterized by dysmorphic facial features, short stature, congenital heart defects, and varying levels of developmental delays. It is a genetic, multisystem disorder with autosomal dominant inheritance and is the most common of the RASopathies. In approximately 50% of patients, NS is caused by variants in the Protein Tyrosine Phosphatase Non-Receptor Type 11 ( PTPN11 ) gene. The aim of this study was to evaluate two patients with a previously reported PTPN11 homozygous variant for the first time and seven other kindred members carrying the same heterozygous variant in terms of clinical, biochemical, genetic, and response to treatment. Methods: Nine patients diagnosed with NS due to the same variants in the PTPN11 gene were included in the study. Results: The median (range) age at diagnosis was 11.5 (6.8-13.9) years and the mean follow-up duration was 4.7 (1-7.6) years. In eight patients (88.9%), short stature was present. The height standard deviation score of the patients on admission was -3.24±1.15. In six of the patients, growth hormone treatment was initiated. Cardiovascular or bleeding disorders were not detected in any of the patients. Three (33.3%) had hearing loss, two (22.2%) had ocular findings and one (11.1%) had a horseshoe kidney. The mean psychomotor development performance score was 84.03±17.09 and the verbal score was 82.88±9.42. Genetic analysis revealed a variant in the PTPN11 gene [c.772G>A; (p.Glu258Lys)] that had been previously described and was detected in all patients. Two patients were homozygous for this variant and short stature was more severe in these two. Conclusion: A previously described in PTPN11 affected nine members of the same kindred, two with homozygous inheritance and the remainder being heterozygous. To the best of our knowledge, these are the first homozygous PTPN11 case reports published, coming from two related consanguineous families.

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“…Notably, our patient presented with non-immune hydrops and limited facial features at birth, whereas the cardiac, lymphatic, and growth manifestations appeared later during infancy. Interestingly, although a wide spectrum of ocular manifestations has been described in NS, limited data have been reported regarding vascular tortuosity [6]. Vascular tortuosity has been reported as a rare ocular finding in syndromic patients with congenital heart diseases, that could be attributed to hypoxaemia and cyanosis [7].…”

Section: Discussionmentioning

confidence: 99%

A Rare Heterozygous LZTR1 Mutation in an Infant with Noonan Syndrome Running Title: LZTR1 Variant in Noonan Syndrome

Rallis¹,

Baltogianni²

2022

JCR

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Background: Noonan syndrome (NS) is a genetically heterogeneous disorder, with several causative variants identified. Up to date, novel leucine zipper-like transcriptional regulator-1 (LZTR1) variants have been reported in a few cases with Noonan syndrome. Case Report: We report the case of a male infant with the phenotypic characteristics of Noonan syndrome, unusual ocular findings, and a LZTR1 variant. Our patient was born prematurely, with antenatal diagnosis of non-immune hydrops, and unremarkable amniocentesis for known Noonan variations. He had dysmorphic features (low set ears, wide nasal bridge, undescended testes), normal weight, and length. After one month of age he developed pulmonary stenosis, and significant extrauterine growth restriction, whereas ocular examination revealed retinal vascular tortuosity. He was discharged at seven months of corrected gestational age, on nocturnal low flow oxygen. Based on van der Burgt's criteria the diagnosis of NS was established. Whole exome sequence analysis revealed a heterozygous variant in the LZTR1 gene (NM_006767.4):c.27delG (p.(Gln10Argfs*15). Conclusion: Given that new LZTR1 mutations may be identified, the evaluation of an extended genetic panel should be applied in suspected NS cases.

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A Narrative Review of the Ocular Manifestations in Noonan Syndrome

Cited by 11 publications

References 37 publications

Systematic ophthalmologic evaluation in cardio‐facio‐cutaneous syndrome: A genotype–endophenotype correlation

Systematic ophthalmologic evaluation in cardio‐facio‐cutaneous syndrome: A genotype–endophenotype correlation

Clinical Variability in a Noonan Syndrome Family with a Homozygous PTPN11 Gene Variant in Two Individuals

A Rare Heterozygous LZTR1 Mutation in an Infant with Noonan Syndrome Running Title: LZTR1 Variant in Noonan Syndrome

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