Dear Editor,

Jacobsen syndrome is a genetic disorder caused by a partial deletion of the 11q chromosome, and is characterized by psychomotor retardation, facial dysmorphism, abnormal platelet function, malformations of the heart, kidneys, and digits, as well as hearing impairment [1]. Common ocular findings in Jacobsen syndrome include hypertelorism, epicanthal fold, ptosis, downslanting palpebral fissures, and strabismus, which reflect the characteristic craniofacial abnormalities [2]. Interestingly, there have been a few reports of Jacobsen syndrome patients with characteristic retinal lesions resembling familial exudative vitreoretinopathy (FEVR), raising the possibility of a relevant association [3,4].

Here, we report a novel case of FEVR in a Korean patient diagnosed with Jacobsen syndrome. This study was approved by the Institutional Review Board at Samsung Medical Center (No. 2024-09-079). Written informed consent for publication was obtained from the patient’s parents.

A female infant was referred to the ophthalmology unit in Samsung Medical Center at 1 month of age for an assessment of ocular involvement related to Jacobsen syndrome. The patient was born at 38 weeks of gestation, weighing 2,740 g. On general examination, the patient showed polydactyly, hearing loss, thrombocytopenia, tricuspid valve disease, and mild left renal pelvis dilatation, all consistent with Jacobsen syndrome. Chromosomal microarray analysis confirmed Jacobsen syndrome with a chromosomal deletion of 11q24.1-q25.

Initial ophthalmologic examination was conducted at 1 month of age. Anterior segment examination revealed no remarkable findings in both eyes. Indirect ophthalmoscopic examination revealed bilateral tortuous vessels and temporal peripheral avascular retina. A lesion in the right eye resembled ridge in stage 2 of retinopathy of prematurity (Fig. 1A, 1B), and an extraretinal fibrovascular proliferation-like temporal lesion with retinal fold was observed in the left eye (Fig. 1C, 1D). Mild macular dragging was noted in the left eye. Fluorescein angiography with RetCam3 (Natus) confirmed retinal neovascularization in both eyes (Fig. 1E-1H). Subsequently, laser photocoagulation was performed on the avascular peripheral retina of both eyes. Following treatment, new vessels regressed bilaterally, and fundus findings remained stable until the latest follow-up at 5 years of age (Fig. 1I-1L).

Chromosomal microarray analysis revealed a 12.2-Mb deletion at the 11q24.1-q25 locus, confirming Jacobsen syndrome (Fig. 1M). Additionally, duplications in 3p26.3 and 16p11.2 were found but were considered benign copy number variants. Whole exome sequencing was performed to investigate genes relevant to FEVR, but no pathogenic variants in the known FEVR-associated genes were detected.

The etiology of FEVR is complex; pathogenic variants in FZD4, LRP5, TSPAN12, and NDP disrupt Wnt signaling and impair retinal vascular development [4]. Among these, FZD4, located on 11q14.2, is of particular interest because a single loss-of-function mutation is sufficient to produce FEVR phenotypes [5]. In our patient, however, neither a deletion involving FZD4 nor a pathogenic variant in this gene was detected. Although no variants were identified in known FEVR genes, several reports have linked terminal 11q deletions to FEVR-like peripheral vascular abnormalities. For example, Uto et al. [3] reported retinal vessel abnormalities and avascular retina linked to a deletion at 11q23.3, while Garcia et al. [4] observed macular dragging and extensive retinal avascularity associated with a t(2;11) (q37;q24) translocation, suggesting that the proximity of these gene loci could influence retinal development.

Our genetic analysis was limited to chromosomal microarray and whole exome sequencing, which cannot reliably detect balanced rearrangements, complex structural alterations or pathogenic changes in non-coding regions. Therefore, undetected disease-causing variants might remain.

In conclusion, we describe bilateral retinal vascular abnormalities that are clinically consistent with FEVR in a South Korean child with Jacobsen syndrome. Because the 11q deletion does not encompass any known FEVR-associated genes and sequencing revealed no pathogenic variants in those genes, a direct genetic association cannot be confirmed. We interpret these findings as a FEVR-like phenotype occurring in the context of a known 11q24.1-q25 deletion. The co-occurrence of these two rare conditions, supported by similar case reports, raises the possibility that genes or regulatory elements within the deleted segment could influence retinal angiogenesis [3,4]. We therefore recommend retinal examinations in patients diagnosed with Jacobsen syndrome to facilitate early detection and management of retinal abnormalities.