Year: 2026
Type: article
Study design: Case Report
Abstract: Cataracts can be familial or syndromic. Early detection during fetal scan should prompt referral to an ophthalmologist. Examination of parents should be mandatory, as in our case, where we got a clue to the diagnosis of Nance Horan Syndrome and confirmed it by molecular testing. This syndrome can have a bearing on the intellect of the child and future progeny. Parents can be accordingly counseled and told for early examination of the child so that surgery is performed within the critical period to prevent amblyopia. A 34-year-old female G2P1L1 reported to our center at 28 weeks for a second opinion for congenital fetal cataract. Her case records showed a normal combined first trimester screening. Her anomaly scan at 23 weeks gestation had raised a suspicion of fetal cataract. The firstborn of the patient was a female child aged 7 years with no systemic problems. Ultrasound done with the C1-5D transducer (Voluson E6, GE Healthcare, Austria) showed the presence of bilateral lenticular opacities suggestive of fetal cataract. (Figure 1a) No other ocular or extraocular abnormality was apparent, and the fetal growth was appropriate for gestational age. After genetic counseling, the patient was offered amniocentesis, which she declined. Maternal TORCH serology was negative. She was then referred to an ophthalmologist for counseling. On examination of the mother, visual acuity was decreased in both eyes, although she was asymptomatic. She had bilateral cataracts with a Y-shaped cataract in her left eye and a wedge-shaped opacification in addition to opacities on the posterior Y suture. (Figure 2a and b). The rest of her physical examination was normal, and she was advised to bring the baby as soon as possible after birth. She delivered a female baby at term weighing 2.9 kg. Ocular findings in the neonate at 2 months were consistent with bilateral diffuse significant cataract and microphthalmia (Figure 1b). Surgery was planned for both eyes at the same time, and the child was visually rehabilitated. (a) Transabdominal USG (grey scale B mode) showing lenticular hyperechogenicity (arrows) in both orbits (axial view) suggestive of fetal cataract. (b) Right eye of the baby at 2 months showing diffuse cataract. The left eye showing a cloudy lens in a dilated pupil against a red glow. Both images were taken under a microscope. (a) Right eye of the mother of the proband showing opacification on the posterior Y suture of the lens (thick arrows) and a wedge-shaped cataract (thin arrow). (b) Left eye showing Y-shaped cataract (arrow). Both images have been taken in a dilated pupil on a slit lamp. Whole exome sequencing for the baby revealed a novel heterozygous likely pathogenic variant in the NHS gene (ENST00000676302.1), c.958C>T (p.Gln320Ter), maternally inherited (confirmed on Sanger sequencing). The variant results in a stop codon and premature truncation of the protein at codon 320. This variant was not previously reported in the 1000 genomes and GnomAD databases, and the reference codon is preserved among species. The variant in the NHS gene was not present in the elder sibling and father. Congenital cataract has an incidence of 2.2–2.4 per 10 000 births.1 It is estimated that ∼50% of the bilateral congenital cataracts have a genetic etiology, and 8–25% are inherited, with autosomal inheritance being the most common mode.2 Causes of congenital cataracts include TORCH infections, medications and metabolic disorders, as well as syndromic associations like Lowe syndrome, Alport syndrome, Walker Warburg syndrome, Chondrodysplasia punctata, Smith-Lemli-Opitz syndrome and Nance Horan syndrome. However, ∼50% are idiopathic. Therefore, it is important to work toward an etiology so that a syndromic cause is not missed. The fetal cataract in our case was a part of Nance-Horan syndrome, which is an X-linked dominant disorder. Affected males manifest with dense nuclear cataracts along with other ocular (microphthalmia, microcornea) and extra-ocular anomalies, while carrier females might have milder manifestations like Y-sutural cataracts with slightly reduced vision.3 These posterior lenticular opacities are a sensitive marker for Nance Horan Syndrome if they have associated facial features. However, without them, the etiology of cataracts becomes a challenge, as female carriers exhibit a spectrum with manifestations ranging from mild to severe. Skewed X-inactivation can cause the variability of clinical manifestations in females. Variants in the NHS gene (Xp22.13 region), most commonly truncating mutations besides copy number variants and gene disruption by balanced translocations, also can cause this condition.4 Genetic counseling becomes very important when bilateral fetal cataract is documented. It is particularly challenging in X-linked disorders where mothers exhibit subtle symptoms, but affected males can have severe manifestations. Our proband (female) had a diffuse opacity in both eyes, with the mother having a Y-shaped cataract, and these can be progressive with implications for vision development. It is therefore important to intervene at the earliest. Without facial features, the search for an etiology becomes a challenge. A genetic test was ordered based on clinical suspicion, which confirmed the diagnosis. The mother had no other features suggestive of the disorder, and the girl child had atypical presentation of the cataract, which was diffuse as well as associated with microphthalmia. The diagnosis of NHS has important genetic implications for future offspring because 30% of affected males may have intellectual disability.5 Knowledge of genetic variation and syndrome provides us with the option of prenatal invasive testing in the subsequent pregnancies. This case highlights the importance of examining fetal orbits in both the first and second trimesters. In cases of fetal cataract, detailed orbital biometry is crucial to further characterize the phenotype, in addition to a thorough investigation of both the fetus and the family. Unilateral cataracts are usually isolated and not associated with systemic disease, but bilateral cataracts demand extensive investigations. The lens opacities can be missed in the newborn examination, leading to amblyopia and poor visual outcomes. A multidisciplinary approach after detection of cataract in the fetus should involve timely referral to an ophthalmologist and genetic work-up to establish the etiology. This would help in tailored counseling and salvage vision. Ravneet Bhatia (Writing—original draft [equal]) None declared. None declared. Patient consent was obtained for using images for this case report.
Source: QJM
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7140611528