FRMD7-Related Infantile Nystagmus

Clinical characteristics: FRMD7-related infantile nystagmus (FIN) is characterized by either the onset of horizontal, conjugate, gaze-dependent nystagmus in the first six months of life or periodic alternating nystagmus (with cyclical changes of nystagmus direction) of infantile onset. Binocular vision and color vision are normal and visual acuity is typically better than 6/12. An abnormal head posture is seen in approximately 15% of affected individuals. The eyes are structurally normal and electrophysiologic studies (e.g., visual evoked potential, electroretinogram) are normal. Affected females report slightly better visual acuity than affected males; however, no differences between males and females in the amplitude, frequency, and waveform of nystagmus are observed.

Diagnosis/testing: The diagnosis is based on clinical findings (including, when possible, ocular motility recordings). Identification of a hemizygous (in a male proband) or heterozygous (in a female proband) pathogenic variant in FRMD7 by molecular genetic testing can establish the diagnosis if clinical features are inconclusive.

Management: Treatment of manifestations: Correction of refractive errors as early as possible. Prisms may be useful in those with binocular vision whose nystagmus is dampened by convergence. Memantine and gabapentin can improve visual acuity, intensity of nystagmus, and foveation. Surgical approaches include: the Anderson-Kestenbaum procedure (surgery of the extraocular muscles to shift the null zone to the primary position) in order to correct anomalous head posture and horizontal rectus tenotomy to improve the waveform of the nystagmus and visual function.

Surveillance: Regular monitoring, especially during childhood, to evaluate visual acuity and development of refractive errors, strabismus, and/or amblyopia.

Genetic counseling: FIN is inherited in an X-linked manner. Affected males transmit the pathogenic variant to all of their daughters and none of their sons. Women who are carriers have a 50% chance of transmitting the pathogenic variant in each pregnancy. Carrier testing for at-risk female relatives and prenatal testing for a pregnancy at increased risk are possible once the pathogenic variant has been identified in the family.