History of present illness
A 9-year-old girl was referred for progressively decreasing central vision with additional impairment of both night and peripheral vision.
Examination findings
Best-corrected visual acuity was 20/150 in the right eye and 20/70 in the left eye. Eye examination showed normal anterior segment, cells in the vitreous humor, attenuated retinal arterioles, macular atrophy, epiretinal membranes, and diffuse hypopigmentation and pigment mottling in the inferior peripheral retina.
Tests
Optical coherence tomography (OCT) showed a loss of photoreceptors in the macular zone and epiretinal membranes in both eyes ( Fig. 7.1 ).
Goldmann kinetic perimetry showed a concentric visual field loss to a target III-4-e in both eyes.
Questions to ask
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Is there a family history of retinal disease?
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A third cousin, not examined by the authors, who was diagnosed with retinitis pigmentosa (RP) (not as severe as this proband).
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Is there a history of hearing loss from birth?
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None observed (hearing loss would be present in Usher syndrome).
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Is there a history of developmental delay, polydactyly, or dental anomalies?
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None observed (these would be seen in Bardet-Biedl syndrome).
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Is there a history of anosmia and ataxia?
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None observed (these would be seen in Refsum disease).
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Is there a history of seizures, developmental regression, or behavioral changes?
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None observed (all of these would be observed in Batten disease).
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Assessment
A 9-year-old proband with reduction in central, night, and peripheral vision was initially diagnosed as having a diffuse retinal pigmentary degeneration within the spectrum of RP or cone–rod dystrophy.
Differential diagnosis
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RP (rod-cone dystrophy)
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Possibly a form of cone–rod dystrophy
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Batten disease
Working diagnosis
Early-onset severe RP based on family history, night vision impairment, diffuse retinal degeneration, and severe visual field loss
Investigations
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OCT and Goldmann kinetic perimetry, as described earlier.
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Gene testing done with an inherited disease panel (248 genes) that showed a heterozygous pathogenic variant in the RPGRIP1L gene and one variant each in CC2D2A and PDZD7 genes of unknown significance.
Follow-up care
Six months later, the patient was seen for rapidly deteriorating central vision (hand motion vision in each eye), developmental regression, and behavioral changes. The eye examination findings were similar to the initial visit.
The diagnosis of Batten disease was entertained, and the patient was referred to a pediatric geneticist. Exome testing confirmed the diagnosis of Batten disease showing two biallelic pathogenic variants in the PPT1 gene (c.223A>C [p.Thr75Pro] with a sequence change, and c.451C>T [p.Arg151*] that creates a premature translational stop signal) consistent with a diagnosis of autosomal recessive neuronal ceroid lipofuscinosis 1.
Management
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There is no treatment at this point for reversing this condition, although some treatment trials are in progress.
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Parents were counseled about the prognosis of the condition and mortality at an earlier age associated with the diagnosis.
Follow-up care
Continued follow-up care was recommended with pediatrics and referred to neurology to evaluate for seizures and possibly electroencephalogram. One year later, the patient did develop seizures.
Key points
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Batten disease (NCL) is a heterogenous group of lysosomal storage diseases that cause rapid and progressive visual loss, behavioral changes, cognitive decline, and potential seizures. ,
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Batten disease, also known as neuronal ceroid lipofuscinoses (NCL), is inherited in an autosomal recessive pattern, and mutations have been described in ceroid lipofuscinosis neuronal (CLN) genes (CLN1–CLN8 and CLN10–CLN14).
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There is intracellular accumulation of an autofluorescent lipopigment in the neurons leading to their degeneration.
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Peripheral blood smears may show vacuolated lymphocytes ( Fig. 7.2 ).
