Keratitis-ichthyosis-deafness (KID) syndrome is a rare disease caused by mutations in the GJB2 gene. This gene encodes the protein connexin 26, which is essential for gap junctions in the epidermis, inner ear and corneal epithelium. Clinically, it is characterised by dermal hyperkeratotic lesions, sensorineural deafness and chronic keratitis that is difficult to manage. We describe two siblings diagnosed with KID syndrome who were followed up in our department for more than 15 years. Both developed numerous ocular complications associated with chronic keratitis and limbar insufficiency that required multiple keratoplasties, systemic immunosuppression and even keratoprosthesis. This case is noteworthy for the long-term follow-up of this condition and the difficult ocular management, highlighting the importance of a multidisciplinary approach and personalised therapeutic strategies.

This case series describes the therapeutic application of customized scleral lenses via prosthetic replacement of the ocular surface ecosystem (PROSE) in patients with Keratitis-Ichthyosis-Deafness (KID) syndrome. It proposes PROSE or scleral lens wear as a therapeutic option for KID syndrome. Two patients with KID syndrome were successfully fitted with PROSE devices, also referred to as prosthetic devices, and continued with wear. The duration of lens wear ranged from one to seven years. One patient was pediatric with severe disease, and the other an adult with milder disease. The pediatric patient had challenges with application and removal and ultimately discontinued device wear; however, demonstrated improvement in corneal surface health through duration of wear for the right eye. The second patient continued with device wear for seven years, with resolution of recurrent corneal erosions, improved comfort and stabilization of corneal surface health. Both patients had benefit with PROSE device wear. Management of ocular surface disease in KID syndrome can be challenging with limited therapeutic options including poor surgical outcomes. This case series supports the therapeutic application of scleral lenses in patients with KID syndrome. IDEDNIK syndrome is characterized by enteropathy, poor weight gain, growth deficiency, skin manifestations (ichthyosis, erythroderma, and keratoderma), sparse hair, global developmental delay, mild-to-severe intellectual disability, and deafness. Additional manifestations can include liver disease, recurrent infections, and hematologic and ocular manifestations (photophobia, corneal scarring, and keratitis). Reduced serum ceruloplasmin and total copper levels are common. Some individuals have findings on brain MRI (cerebral atrophy, basal ganglia abnormalities, and thin corpus callosum). Death prior to age two years occurs in some individuals due to severe enteropathy or sepsis; in others survival into adulthood is reported. The diagnosis of IDEDNIK syndrome is established in a proband by identification of biallelic pathogenic variants in AP1B1 or AP1S1 by molecular genetic testing. Targeted therapy: Treatment with oral zinc acetate therapy to reduce liver copper overload has been reported to improve behavioral disturbances, skin manifestations, and cognitive function in some individuals. Zinc sulfate may be an alternative, less expensive treatment option. Experience is limited with this targeted therapy. Supportive care: Dietary modification and potential parenteral supplementation for enteropathy; feeding therapy; gastrostomy tube placement as needed; treatment options for skin manifestations include low-dose oral acitretin, skin emollients and topical lactic acid, frequent emollient application and short courses of topical cortical steroids or pimecrolimus ointment, and 50% urea ointments; developmental and educational support; hearing aids as needed for sensorineural hearing loss; community hearing services; standard treatment of seizures and peripheral neuropathy by an experienced neurologist; supportive treatment as needed for liver disease; standard treatment for recurrent infections; supportive treatment as needed for hematologic manifestations, and occasionally transfusion may be necessary; standard treatment of cataracts and other ocular manifestations per ophthalmologist; treatment of cryptorchidism per urologist; treatment of hypothyroidism and growth hormone deficiency per perinatologist; social work and family support. Surveillance: At each visit, assess growth parameters, nutritional status, safety of oral intake, diarrhea, skin and hair manifestations, developmental progress and educational needs, mobility and self-help needs, seizures and peripheral neuropathy, behavioral issues, liver function tests, complete blood count, evidence of aspiration and respiratory infections, and family needs. Audiology evaluation as recommended by audiologist; ophthalmology evaluation for keratitis, cataract, and accommodative esotropia as recommended by ophthalmologist; assess thyroid function and for growth hormone deficiency as recommended by endocrinologist. Evaluation of relatives at risk: Clarify the genetic status of apparently asymptomatic older and younger at-risk sibs in order to identify as early as possible those who would benefit from prompt initiation of zinc acetate treatment. IDEDNIK syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an AP1B1 or AP1S1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the AP1B1 or AP1S1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.

Cogan's syndrome is a condition of unknown origin, classified as a systemic vasculitis. It is characterised by a predilection for the cornea and the inner ear. It mainly affects Caucasian individuals with a sex-ratio close to one. Ophthalmological and cochleo-vestibular involvement are the most common manifestations of the disease. The most frequent ophthalmological type of involvement is non-syphilitic interstitial keratitis. Cochleo-vestibular manifestations are similar to those of Meniere's syndrome. The disease progresses in ocular and ear-nose-throat (ENT) flares, which may occur simultaneously or in isolation. Association with other autoimmune diseases, particularly other forms of vasculitis such as polyarteritis nodosa or Takayasu's arteritis, is possible. Ocular involvement, as well as cochleo-vestibular involvement, can be inaugural and initially isolated. Onset is often abrupt. The characteristic involvement is "non-syphilitic" interstitial keratitis. It is usually bilateral from the outset or becomes so during the course of the disease. It presents as a red, painful eye, possibly associated with decreased visual acuity. Cochleo-vestibular involvement is usually bilateral from the outset. It is characterised by the sudden onset of continuous rotational vertigo associated with tinnitus, rapidly progressive sensorineural deafness. Approximately 30-70% of patients present with systemic manifestations. Deterioration in general status with fever may be present. Laboratory evidence of inflammatory syndrome is associated in 75% of cases. Cogan's syndrome is a presumed autoimmune type of vasculitis, although no specific autoantibodies have been identified. Ocular involvement is usually associated with a good prognosis, with total visual acuity recovery in the majority of cases. In contrast, cochleo-vestibular involvement can be severe and irreversible. Therapeutic management of Cogan's syndrome, given its rarity, lacks consensus since no prospective randomised studies have been conducted to date. Corticosteroid therapy is the first-line treatment. Combination with anti-TNF therapy should be promptly discussed.

We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.

Brittle cornea syndrome type 2 is associated with corneal thinning, joint hypermobility, dental and skeletal issues, osteal fragility, and deafness. We present a rare association of congenital glaucoma with brittle cornea syndrome type 2 and keratoglobus in a patient with a novel PRDM5 gene mutation. Our case underscores the importance of genetic testing for early clinical diagnosis and tailored surgical approaches.