Ocular findings in Noonan syndrome: a retrospective cohort study of 105 patients

Abstract

The aim of this retrospective study is to describe ocular findings in a large Noonan syndrome cohort and to detect associations between ocular features and genetic mutations that were not found in earlier studies. We collected ophthalmological and genetic data of 105 patients (median age, 12 years; range, 0–60 years) clinically diagnosed as Noonan syndrome. The ocular findings were linked to the genotypes. All patients with Noonan syndrome showed multiple abnormalities in the categories of vision and refraction, external ocular features, ocular alignment and motility, anterior ocular segment, and posterior ocular segment. In total, 50 patients have NS due to a mutation in PTPN11. Permanent visual impairment (bilateral best-corrected visual acuity < 0.3) was found in 7 patients, including patients with a mutation in RAF1, SHOC2, and KRAS. Keratoconus was found in 2 PTPN11 positive patients, and prominent corneal nerves were observed in a patient with a SOS1 mutation.Conclusions: This study shows an overview of ocular abnormalities in Noonan syndrome, including permanent visual impairment caused by binocular optic nerve abnormalities and nystagmus. Delay in ophthalmological diagnosis is still present, also in patients with visual impairment. All Noonan syndrome patients should have a complete ophthalmological examination at the time of diagnosis. What is Known: • Although we discover more pathogenic mutations in patients with Noonan syndrome, Noonan syndrome still is a clinical diagnosis • Ocular features of Noonan syndrome are characterized by developmental anomalies of the eyelids and associated with other ocular abnormalities in childhood (including refractive errors, strabismus and amblyopia). What is New: • There seems to be a delay in the ophthalmological diagnosis and awareness of the broad variety ofophthalmological features including refractive errors and visual impairment in Noonan syndrome is needed. All children should have a full ophthalmological examination at the time of diagnosis. • Permanent visual impairment (best-corrected visual acuity < 0.3) is found in patients with mutations in RAF1, SHOC2, and KRAS and the cause is probably a developmental disorder of the optic nerves.

Clinical orofacial and myofunctional manifestations in an adolescent with Noonan Syndrome: a case report

“…Other clinical alterations were also verified and ratified by the literature, such as triangular face, external palpebral fissure diverted downward, low implantation of the auricular pavilion, with thickening of the auricular helix and short neck and high anterior hair implantation 7,11 , ocular hypertelorism and telecanthus 7,11,19 , nystagmus 20 , short stature 18 , and hearing loss 21 .…”

Anterior lenticular opacities in Costello Syndrome

“… 6 The etiology behind may be a common mutation in the gene since few studies have reported cataract in patients with RASopathy (Noonan's syndrome). 7 …”

Absence of the c.169+50delTAAACAG mutation of SOD1 gene in a sample of keratoconus patients in Brazilian population

“…Several studies of genetic screening found in the literature have investigated this gene as well as other such as VSX1, LOX, TIMP3, DOCK9, and collagen genes and identified genetic changes that may be related to the disease. Nevertheless, these results alone are not consistent enough to consider these genetic agents as disease-triggering [ 23 , 24 , 35 – 39 ].…”