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Short Stature With Optic Atrophy and Cone Dystrophy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 26-year-old man presented with reduced visual acuity in both eyes since early childhood. He had short stature (1.52 m [−3.6 SD]) and progeroid appearance. His parents and brother had normal stature. His medical history was significant for frequent upper respiratory tract infections since infancy. He had no intellectual disability, neurologic symptoms, or hearing impairment. There was no family history of visual impairment or neurologic disorders. His best-corrected visual acuity was 20/80 OD and 20/50 OS. Intraocular pressure was normal. He could not identify any Ishihara color plate. Slitlamp examination was unremarkable. Dilated fundus examination results showed diffuse optic atrophy (OA) and fine pigmentary mottling changes at the fovea in both eyes (Figure 1A). Electroretinography (ERG) showed normal dark-adapted responses and severely reduced light-adapted responses. Optical coherence tomography showed thinning of retinal nerve fiber layers and disruption of outer nuclear layers and the ellipsoid zone at the center of the fovea (Figure 1B). Leber hereditary optic neuropathy sequencing was negative for 3 hot spot mutations.

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Short stature, OA, Pelger-Huët anomaly syndrome

D. Order whole-exome sequencing

Diagnosis of hereditary OA is challenging for ophthalmologists, especially when combined with retinal dystrophy. Because the optic nerve may have variable degrees of temporal pallor in cone dystrophy, cone disorders should be included in the differential diagnosis. Optic atrophy is usually accompanied by CACNA1F congenital stationary night blindness,1 or it can be a late manifestation of retinitis pigmentosa. However, patients with congenital stationary night blindness typically have normal fundus and negative ERGs in scotopic response. Spinocerebellar ataxia and SSBP1 variant also cause OA and variable retinal degeneration.2,3

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Article Information

Corresponding Author: Jinu Han, MD, Institute of Vision Research, Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Eonjuro 211, Gangnam-gu, Seoul 06273, South Korea (jinuhan@yuhs.ac).

Published Online: June 10, 2021. doi:10.1001/jamaophthalmol.2020.5777

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by grant 2020R1C1C1007965 from the National Research Foundation of Korea, which is funded by the Korea government (Dr Han).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
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2.
Jurkute  N , Leu  C , Pogoda  HM ,  et al.  SSBP1 mutations in dominant optic atrophy with variable retinal degeneration.   Ann Neurol. 2019;86(3):368-383. doi:10.1002/ana.25550 PubMedGoogle ScholarCrossref
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Park  JY , Joo  K , Woo  SJ .  Ophthalmic manifestations and genetics of the polyglutamine autosomal dominant spinocerebellar ataxias.   Front Neurosci. 2020;14:892. doi:10.3389/fnins.2020.00892 PubMedGoogle ScholarCrossref
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Maksimova  N , Hara  K , Nikolaeva  I ,  et al.  Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.   J Med Genet. 2010;47(8):538-548. doi:10.1136/jmg.2009.074815 PubMedGoogle ScholarCrossref
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