Table 3.

Disorders to Consider in the Differential Diagnosis of FRMD7-Related Infantile Nystagmus (FIN)

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/FINDistinguishing from FIN 1
Oculocutaneous albinism (OCA) 2, 3OCA1 (OMIM 203100, 606952)
OCA2 (OMIM 203200)
OCA3 (OMIM 203290)
OCA4		 TYR
OCA2
TYRP1
SLC45A2 		ARInfantile nystagmusIn OCA:
  • Hypopigmentation of iris pigment epithelium
  • Hypopigmentation of ocular fundus
  • Foveal hypoplasia
  • Misrouting of axons in optic chiasm
  • Much poorer visual acuity (in all forms of albinism)
  • Poor binocular vision; strabismus is common

Ocular albinism type 1 (OMIM 300500)

 GPR143 XL
  • Infantile nystagmus
  • Normal hair & skin pigmentation
  • X-linked inheritance
Chediak-Higashi syndrome (CHS) LYST ARInfantile nystagmusIn CHS:
  • Partial OCA
  • Immunodeficiency
  • Mild bleeding tendency
  • Neurologic findings during early adulthood
  • ~85% develop the accelerated phase (lymphoproliferative infiltration of bone marrow & reticuloendothelial system)
Achromatopsia AFT6
CNGA3
CNGB3
GNAT2
PDE6C
PDE6H 		ARInfantile nystagmus (pendular or jerk nystagmus in achromatopsia)In achromatopsia:
  • Reduced or complete loss of color discrimination 4
  • Reduced visual acuity
  • Photophobia
  • Small central scotoma
  • Eccentric fixation
  • Absent/markedly diminished ERG photopic response but normal/mildly abnormal scotopic response
  • Characteristic lesion at the fovea w/outer nuclear layer thinning on optical coherence tomography
Blue cone monochromatism
(OMIM 303700)		 OPN1LW
OPN1MW 		XLInfantile nystagmusIn blue cone monochromatism:
  • Reduced visual acuity (but better than in achromatopsia)
  • Photophobia
  • Reduced photopic ERG but well-preserved S cone ERG
X-linked congenital stationary night blindness (CSNB1 and CSNB2) CACNA1F
NYX 		XL
  • Infantile nystagmus
  • Normal color vision
  • Normal fundus examination
In CSNB:
  • Non-progressive retinal findings of reduced visual acuity, defective dark adaptation, refractive error, & strabismus
  • Scotopic ERG shows severely reduced (or absent) b-waves in CSNB1 & reduced but measurable b-waves in CSNB2 (absent b-wave may be referred to as a "negative ERG." FIN can be differentiated from CSNB based on ERG studies.
Leber congenital amaurosis (LCA)See footnote 5.AR
(AD)		Infantile nystagmusIn LCA 6:
  • Visual function usually poor & often w/sluggish or near-absent pupillary responses, photophobia, & refractive errors
  • Visual acuity rarely >6/12
  • Oculodigital sign
  • Extinguished/severely reduced scotopic & photopic ERG 7

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance; XL = X-linked

1.

Bolded text indicates key distinguishing features.

2.

All forms of albinism are characterized by infantile nystagmus. The most common forms of albinism are OCA and X-linked ocular albinism.

3.
4.

When color vision is difficult to test in young children, ERG can be used.

5.

Pathogenic variants in at least 17 genes are known to cause LCA (see Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview).

6.

LCA is a severe dystrophy of the retina typically evident in 1st year of life.

7.

Because measuring visual acuity in infants can be difficult, ERG is the test of choice for distinguishing between FIN and LCA in infants.

From: FRMD7-Related Infantile Nystagmus

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