The introduction of genomic testing into prenatal care has come at a rapid pace and has been met with significant clinical and ethical challenges, specifically when dealing with incidental findings. We present the case of a couple in their first pregnancy who were referred to our institution with isolated fetal cataracts on morphology scan. After an unremarkable infectious disease workup and microarray on an amniocentesis sample, the couple opted for fetal whole-exome sequencing to investigate the cataracts further. This investigation did not find any cause for the cataracts but yielded an incidental finding of a de novo pathogenic variant in the SCN1A gene unrelated to the cataracts. Pathogenic variants in the SCN1A gene are strongly associated with severe myoclonic epilepsy of infancy, or Dravet syndrome. After extensive genetic counseling, the couple decided to terminate the pregnancy at 28 weeks\' gestation based on this finding. This case highlights some of the important clinical and ethical considerations in prenatal genetic diagnosis, particularly in the group of patients in which there is no phenotypic evidence in-utero of the incidental finding. The case demonstrates the value of frameworks and guidelines to guide management decisions for both clinicians and patients.

We describe a child from a consanguineous family born with a rare autosomal recessive disorder affecting junctional adhesion molecule 3 (JAM3) causing profound neurological and ophthalmological injury known as haemorrhagic brain destruction, subependymal calcifications, and congenital cataracts (HDBSCC; MIM# 613730). She was the product of an unremarkable pregnancy and was born near to term but was noted shortly after birth to have congenital cataracts, poor vision, increased muscle tone, seizures, and developmental delay. Her older sister had an identical syndrome and had previously been documented to have homozygous mutations in JAM3. Examination in our patient, although difficult because of bilateral central cataracts, revealed very poor vision, attenuated retinal vessels, optic atrophy, and a retinal haemorrhage in the right eye, implying that abnormal development of the retinas and/or optic nerves may at times play a significant role in the poor vision noted in children with HDBSCC.

Congenital nystagmus (CN) and congenital cataracts are distinct eye diseases and are usually isolated. Cases with CN and congenital cataracts caused by different genes in one family have been rarely reported.
A 27-year-old man presented with CN and congenital cataracts and he underwent cataract extraction 2 weeks after birth. Three years later, he had posterior chamber intraocular lens implantation. The proband\'s mother was only afflicted by bilateral lens opacities. Lensectomy was performed in both eyes at age 15. The proband\'s daughter had bilateral central cataracts and no nystagmus. She had undergone cataract extraction when she was two months old. In this family, 8 affected individuals were affected by bilateral cataracts, and three of them presented with CN. The genetic analysis was performed using a specific Hereditary Ophthalmological Disease Gene Panel on proband and his parents (one of which was a patient). PCR and Sanger sequencing verified the presence of these variants in all members of the family. The novel mutation, c.498-3C > T, in FRMD7 explains why X-Linked recessive inheritance of CN was found in a subset of patients. A heterozygous mutation of the GJA8 gene (c.139G > C), was identified in all patients and thus explains the autosomal dominant pattern of inheritance of congenital cataracts within the family.
This is the first time that FRMD7 and GJA8 gene mutations have been linked to the pathogenesis of a family with both CN and congenital cataracts. The phenomenon of two different genetic patterns coexisting in one family is rare.

The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, cognitive and behavioral impairment and a renal proximal tubulopathy in almost all of the patients. Whereas the ocular manifestations and severe hypotonia are present at birth, the renal involvement appears within the first months of life. Patients show progressive growth retardation and may develop a debilitating arthropathy. Treatment is symptomatic and life span rarely exceeds 40 yr. The causative OCRL gene, encodes an inositol polyphosphate 5-phosphatase. OCRL mutations were not only found in classic Lowe syndrome, but also in milder affected patients, classified as having Dent-2 disease. There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of enzyme function. Researchers have conducted a large amount of work to understand the etiology responsible for the disease. However, the mechanisms leading to the clinical manifestations are still poorly understood and we are far from an effective therapy. In this review, we have included well-established findings and the most recent progress in understanding Lowe syndrome and Dent-2 disease.

GFER-related mitochondrial encephalomyopathy has been previously described only in 3 siblings of a consanguineous Moroccan family. Their phenotype included congenital cataracts, hypotonia, developmental delay, and sensorineural hearing loss. Multiple mitochondrial respiratory chain complex deficiencies were identified on muscle biopsy. We describe a now-19-year-old woman with adrenal insufficiency, lactic acidosis, congenital cataracts, and respiratory insufficiency secondary to mitochondrial disorder, who was reported by North et al (1996) as a toddler. Compound heterozygous GFER mutations c.373C>T (Q125X) and c.581G>A (R194 H) were recently discovered in this patient. The purpose of this report is (1) to expand the phenotype this ultra-rare disorder and (2) to provide a review of the literature describing the unique finding of adrenal insufficiency in patients with molecularly confirmed disorders of mitochondrial metabolism.