Table 2.

Conditions/Syndromes Associated with Infantile Glaucoma

DisorderGene(s)MOIClinical Features
Eye FindingsOther
Aniridia PAX6
WT1 1		AD
  • Complete or partial iris hypoplasia w/assoc foveal hypoplasia, resulting in ↓ visual acuity & nystagmus
  • Presents in early infancy
  • Frequently assoc w/other ocular abnormalities, often of later onset, incl cataract, glaucoma, & corneal opacification& vascularization
May occur either as an isolated ocular abnormality w/o systemic involvement or as part of WAGR syndrome 1
Anterior segment dysgenesis syndromes (e.g., Peters Plus syndrome)See footnote 2.Phenotypically & genotypically distinct from PCG in general, but severe or advanced PCG can be difficult to distinguish clinically from some of the anterior segment dysgenesis syndromes (e.g., Peters anomaly)Peters Plus syndrome: developmental delay, mild to severe ID, cleft lip, cleft palate
Axenfeld-Rieger anomaly (anterior segment disorder) FOXC1
PITX2 		AD
  • Presents w/posterior embryotoxon & (variably) iris strands adherent to Schwalbe's line, iris hypoplasia, focal iris atrophy, & ectropion uveae.
  • Glaucoma develops in ~50% of persons but is more common in those w/central iris changes & marked anterior iris insertion
  • Always bilateral, but may be distinctly asymmetric
May occur in the setting of Axenfeld-Rieger syndrome (OMIM 180500): dysmorphic features, dental anomalies, sensorineural hearing loss, cardiac malformations, endocrine & orthopedic abnormalities
MicrocorneaUnknown 3
  • Corneal diameter <10 mm
  • Can be assoc w/glaucoma & other ocular anomalies incl congenital cataracts, sclerocornea, & corneal plana
May be a feature of systemic syndromes
Congenital hereditary endothelial dystrophy (CHED) (OMIM 217700) SLC4A11 AR
  • Bilateral corneal opacification
  • May be difficult to distinguish from microcornea, but corneal diameter & IOP are usually normal in CHED
  • The primary defect in the corneal endothelium leads to corneal edema & opacification.
  • CHED & CG are known to coexist; exact incidence unknown 4
Sensorineural hearing loss
Lowe syndrome OCRL XL
  • Dense congenital cataracts are found in all affected boys, infantile glaucoma in ~50%
  • All boys have impaired vision; corrected acuity rarely >20/100
  • Almost all affected males have some ID
Congenital hypotonia, delayed development, proximal renal tubular dysfunction (renal Fanconi type), progressive chronic renal failure and ESKD after age 10-20 yrs
Neurofibromatosis type 1 NF1 AD
  • Iris Lisch nodules
  • CG rarely observed
Multiple café au lait spots, axillary & inguinal freckling, cutaneous neurofibromas, learning disabilities in ≥50% of persons
Nance-Horan syndrome (OMIM 302350) NHS XLCataract and microcorneaSkeletal features
Sturge-Weber syndrome (OMIM 185300) GNAQ See footnote 5.CG w/assoc angle anomalies in ≤60% of affected personsNevus flammeus of the face, angioma of the meninges

AD = autosomal dominant; AR = autosomal recessive; CG = congenital glaucoma; ESKD = end-stage kidney disease; ID = intellectual disability; MOI = mode of inheritance; WAGR = Wilms tumor-aniridia-genital anomalies-retardation; XL = X-linked

1.

Pathogenic variants or deletions in PAX6 or its control elements are associated with isolated aniridia. Contiguous gene deletions including PAX6 and WT1 are associated with aniridia and the risk of one or more additional manifestations of WAGR.

2.

Anterior segment dysgenesis syndromes are a heterogeneous group of disorders that are usually inherited in an autosomal dominant manner with reduced penetrance.

3.
4.
5.

Somatic mosaic pathogenic variants in GNAQ have been reported in individuals with Sturge-Weber syndrome.

From: Primary Congenital Glaucoma

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