“Ear of the Lynx” Sign in Hereditary Spastic Paraplegia 76

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Dear Editor,Hereditary spastic paraplegia (HSP) 76 is a rare form of spastic paraparesis caused by mutations in CAPN1.It is inherited in an autosomal recessive manner, and about 50 cases have been reported worldwide.1 The clinical presentation of HSP76 varies from pure spastic paraparesis to a complicated form accompanied by ataxia. 2 Diagnosing the disease may often be challenging, but a previous case report suggested that an "ear of the lynx" sign in brain magnetic resonance imaging (MRI) can be useful.3 Here we describe an HSP76 patient, including their brain MRI findings.A 25-year-old female patient presented at our clinic with a 10-year progressive gait disturbance.She had a normal developmental history from infancy through childhood.However, she experienced unsteadiness while walking and sometimes required assistance when going down stairs.Her parents had noticed that her speech had become unclear about 2 years previously.She was diagnosed with type I diabetes mellitus 4 years previously.Her other medical history was unremarkable, and her family history was negative for genetic disease.Her speech was slightly slurred, but a cranial nerve examination including vision, pupil, and eye movements was unremarkable.A motor examination of the upper limbs produced normal findings, while subtle weakness of ankle plantar flexion was noticed along with brisk deep tendon reflexes in both knees as well as ankle clonus.The finger-to-nose test showed bilateral dysmetria and mild terminal tremor.She stood with a wide base and exhibited multiple side steps during the tandem gait test.Other aspects of her nervous system appeared normal.Serological testing for human immunodeficiency virus, human T-lymphotropic virus 1, vitamin B12, paraneoplastic antibodies, and a vasculitis panel produced negative findings.Brain MRI showed mild cerebellar atrophy in the upper part of the anterior and posterior lobes (Fig. 1A), and revealed vertical and horizontal T2-hyperintense signals at the level of the ventral pons (Fig. 1B).In addition, T2 hyper-/T1 hypointense signals were observed resembling a tuft of hair at the tips of the frontal horns of the lateral ventricles (Fig. 1C and D).Genetic tests for dentatorubral-pallidoluysian atrophy and spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, and 17 were normal.The targeted sequencing for HSP identified two compound heterozygous variants in CAPN1: c.1730-2A>G and c.1442G>A (NM_001198868.2).The c.1730-2A>G variant was novel and was classified as a likely pathogenic variant according to the criteria established by the American College of Medical Genetics and Genomics.4 The classification was supported by the following evidence: 1) the variant represents a null variant in a gene where loss of function is a recognized disease mechanism, 5 and 2) it is not present in controls in the gnomAD database.Similarly, the c.1442G>A (p.Arg481Gln) variant was also classified as likely pathogenic, based on following evidence: 1) it is located in a region known to have a high mutation density and/or within a critical and well-established functional domain that lacks benign variations, 2) it is not observed in East Asian control samples in the gnomAD database, 3) several computational models predict a deleterious effect on the gene or its