Background: Wieacker-Wolff syndrome is an ultra-rare disease with X-linked inheritance characterized by arthrogryposis, intellectual disability, microcephaly, and distal limb muscle atrophy. Ophthalmic abnorm-alities such as ptosis, strabismus, and oculomotor apraxia have been reported in half of the patients. Wieacker-Wolff syndrome female-restricted (WRWFFR) is an even rarer disease recently used for females with a more severe phenotype.Materials and Methods: Clinical geneticist and ophthalmic examination, neuroimaging, and exome sequencing.Results: A 4 years-old girl with developmental and language delay, microcephaly, camptodactyly, digital pads, and arthrogryposis was identified by the clinical geneticist. Ophthalmic examination revealed deep-set eyes, high hyperopic astigmatism in both eyes, and reduced retinal nerve fiber layer thickness measured by optical coherence tomography. Exome sequencing identified a novel, probably pathogenic variant in the ZC4H2 gene NM_018684.3:c.145A>T p. (Lys49*) in heterozygosis.Discussion: WRWFFR is an ultra-rare disease with X-linked inheritance by variants in the ZC4H2 gene. This case reports a girl with a novel nonsense variant in the ZC4H2 gene and a severe phenotype; previous reports have identified WRWFFR in females with large deletions and nonsense mutations which could explain the manifestations in the current case report. A complete ophthalmic examination should be considered in patients with WRWFFR to detect the possibly associated optic nerve involvement and other previously described manifestations such as ptosis and strabismus.

Traboulsi syndrome is a rare genetic disorder characterized by facial dysmorphism, lens subluxation, anterior segment anomalies, and spontaneous filtering blebs. The syndrome is due to mutations in the ASPH gene, which plays a crucial role in the development and maintenance of the lens. This case report describes the clinical and genetic findings in a Mexican male with Traboulsi syndrome, highlighting the identification of a novel ASPH variant. A 21-year-old male presented with trauma to the right eye while playing soccer. He had a history of lens subluxation and dysmorphic facial features. Ophthalmic examination revealed right eye lens subluxation into the anterior chamber (with signs of a previous episode of acute angle closure) and left eye posterior and inferior lens subluxation with sectorial iris atrophy. Genetic analysis identified a pathogenic ASPH variant (NM_004318.3:c.1892G>A, p.Trp631*) and a novel likely pathogenic variant (deletion of exons 20–21), confirming Traboulsi syndrome. This is the first instance of Traboulsi syndrome in the Mexican population. The absence of spontaneous filtering blebs in this patient supports previous reports of the wide phenotypic variability that could be related to the type of mutation. This novel ASPH variant expands the known genetic heterogeneity of Traboulsi syndrome.

Background: The spinocerebellar ataxias (SCA) are a group of multiple inherited disorders. The molecular diagnosis of the specific type of SCA is challenging due to the diversity of hereditary patterns and genetic anomalies. Certain key clinical features can help shorten the differential diagnosis. Cases: At our center, we evaluated three patients presenting with gait disturbances. They were assessed by multiple hospital departments, and, due to suspected spinocerebellar ataxia, comprehensive genetic and ophthalmologic testing was performed, leading to diagnoses of SCA2, SCA7, and SCAR32. These cases highlight the importance of multidisciplinary evaluation for accurate diagnosis of complex neurogenetic disorders. All patients experienced prolonged diagnostic delays, requiring years of multiple consultations across different hospitals before reaching a definitive diagnosis. Literature Review: Among all published reports of patients with SCA, we consider that five distinct key clinical features can categorize many patients suffering from a possible SCA into different groups and reduce the potential differential diagnosis. Only two types of SCA presented macular anomalies, ten optic nerve involvements, one erythrokeratodermia, four hearing losses, and four dementias. Conclusions: Early referral to a multidisciplinary evaluation might help narrow the differential diagnosis of specific types of SCA, guiding the diagnostic work-up toward SCA1 and SCA7 in patients with macular involvement, or toward SCA1, SCA2, SCA3, SCA7, SCAR3, SCAR9, SCAR21, SCAR29, SCAR31, and SCAX3 in those with optic nerve involvement.

Background: Genetic eye diseases (GEDs) comprise a heterogeneous group of hereditary and de novo disorders that involve all ocular structures, including the retina, optic nerve, vitreous, anterior segment, and ocular development. Their marked clinical and genetic heterogeneity frequently delays diagnosis and access to genetic counseling, multidisciplinary management, and emerging gene-based therapies. Although ophthalmic deep phenotyping remains essential, we propose an approach that prioritizes genetic analysis, particularly in under-resourced healthcare settings with limited access to advanced imaging and electrophysiological tests. Methods: We conducted a retrospective observational study of 101 consecutive patients with suspected genetic eye diseases. All were evaluated at a tertiary referral center in northeastern Mexico between January 2020 and August 2023 through comprehensive ophthalmologic examination supplemented by optical coherence tomography, visual-field testing, and fundus photography when clinically indicated. All patients were offered early molecular testing while awaiting future tests, such as electrophysiological testing or further referral visits. Molecular testing consisted of an ophthalmology-focused next-generation sequencing multigene panel. Results: The primary outcome was molecular diagnostic yield. A clinically actionable molecular diagnosis was established in 45 patients, corresponding to an overall molecular diagnostic yield of 44.6%. A total of 165 variants were identified, including 70 pathogenic, 16 likely pathogenic, 43 variants of uncertain significance, and 36 likely benign variants. Usher syndrome was the most frequent molecular diagnosis (10/45, 22.2%), comprising nine patients with USH2A-associated Usher syndrome type 2 and one patient with MYO7A-associated Usher syndrome type 1B, followed by Stickler syndrome (8/45, 17.8%), oculocutaneous albinism (3/45, 6.7%), and Alström syndrome (2/45, 4.4%). Autosomal recessive disorders represented the predominant inheritance pattern (68.9%). Conclusions: Our findings support ophthalmology-focused multigene panels as an effective first-line diagnostic strategy for patients with suspected genetic eye diseases. Early molecular testing may shorten the diagnostic odyssey, optimize resource utilization, facilitate precision diagnosis and genetic counseling, and guide future targeted deep phenotypic evaluation, prognosis, and eligibility for emerging gene-specific therapies.