Table 4.

Genes of Interest in the Differential Diagnosis of Stickler Syndrome

Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder
ARR3
CPSF1
LRPAP1
P4HA2
PRIMPOL
SCO2
SLC39A5
ZNF644
High-grade myopia (OMIM PS160700)AD
AR
XL 1
Refractive error ≥ −6 diopters
ATOH7 Nonsyndromic congenital retinal nonattachment (NCRNA) (OMIM 221900)ARCongenital insensitivity to light, massive retrolental mass, shallow anterior chamber, microphthalmia, & nystagmus in otherwise normal individuals
BMP4 BMP4-related disorder 2ADHigh myopia, congenital hypoplasia of the vitreous, retinal detachment, high-arched palate, retrognathia, sensorineural hearing loss
GZF1 GZF1-related disorder 2ARHigh myopia, retinal detachment, chorioretinal coloboma, hearing loss, joint laxity & dislocations, kyphoscoliosis, talipes
KCNJ13 Snowflake vitreoretinal degeneration (OMIM 193230)ADCataract, fibrillar degeneration of the vitreous, & peripheral retinal abnormalities incl minute, shiny, crystalline-like deposits resembling snowflakes. Individuals show a low rate of retinal detachment.
LOXL3 LOXL3-related disorder 2ARMyopia, vitreous detachment, flat midface, cleft palate, micrognathia, mild conductive hearing loss, joint laxity
LRP2 LRP2-related disorder 2 (See also Donnai-Barrow Syndrome.)ARMyopia, retinal detachment, abnormal vitreous, flat midface, retrognathia, joint pain
VCAN VCAN-related vitreoretinopathy (incl Wagner syndrome & erosive vitreoretinopathy)AD"Optically empty vitreous" on slit lamp exam & avascular vitreous strands & veils, myopia, presenile cataract, night blindness of variable degree assoc w/progressive chorioretinal atrophy, retinal traction & retinal detachment at advanced stages of the disease & ↓ visual acuity. 1st signs usually become apparent during early adolescence, but onset can be as early as age 2 yrs.
1.

ARR3-related high-grade myopia is inherited in an X-linked manner. CPSF1-, P4HA2-, PRIMPOL-, SCO2-, SLC39A5-, and ZNF644-related high-grade myopia are inherited in an autosomal dominant manner. LRPAP1-related high-grade myopia is inherited in an autosomal recessive manner.

2.

Pathogenic variants in BMP4, GZF1, LOXL3, and LRP2 have been reported in individuals with features overlapping those of Stickler syndrome [Nixon et al 2019, Nixon et al 2022].

From: Stickler Syndrome

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