Neonatal SCA 2 Presenting With Choreic Movements and Dystonia With Dystonic Jerks, Retinitis, Seizures, and Hypotonia

Autosomal-dominant SCAs are a clinically, genetically, and pathologically heterogeneous group of degenerative disorders, mainly affecting the cerebellum and its connections. Although most commonly characterized by progressive cerebellar symptoms, a plethora of so-called nonataxia features may develop and become a diagnostic challenger. SCA2 is caused by an abnormal expansion of a CAG repeat in Ataxin-2 (ATXN2) gene, located on chromosome 12 (12q24.1). Normal CAG alleles range from 15 to 32 repeats. The disease usually presents with adult-onset progressive cerebellar ataxia, dysarthria, nystagmus, slow saccadic eye movements, and peripheral neuropathy.1, 2 Childhood onset is uncommon and is frequently associated with larger triplet expansions (>100 repeats) and presents with multisystem involvement beyond the aforementioned neurologic symptoms, such as developmental delay, hypotonia, pigmentary retinopathy, seizures, dysphagia, and early death.3-6 Herein, we describe a patient with neonatal-onset SCA2 that presented with choreic movements and dystonia with dystonic jerks, retinitis, seizures, and hypotonia as prominent clinical features instead of ataxia, resembling a global encephalopathy. A 1-year-old Brazilian girl presented to our hospital with motor developmental delay. The patient was born to unrelated Brazilian parents (without known ancestry) at term after an uncomplicated pregnancy. During the neonatal period (first month), she presented hypotonia, dysphagia, and frequent gastroesophageal reflux. Tonic seizures started at the third month of age and temporally resolved with low doses of carbamazepine. Over the subsequent months, the child remained hypotonic with increased feeding difficulties, and involuntary movements started, characterized by choreic movements and dystonia with dystonic jerks (see Video). After the first year, seizures returned and carbamazepine was replaced by valproate with good response. She never acquired head control or appropriated tonus. There was no obvious dimorphism. The family history was remarkable for a dominant undetermined ataxia on the father's side of the family (Fig. 1). Her father developed ataxia and slow saccadic eye movements at around 30 years of age. Neurological examination revealed decreased tonus and global decreased tendon reflexes. She did not track to sound, and the parents had a concern about her ability to see and hear. She was unable to reach for objects with her hands as a result of appendicular ataxia. Visual fixation was poor, and erratic eye movements and ophthalmoparesis were observed. Fundoscopy disclosed abnormal retina, with white dots, suggesting retinitis punctata albescens (Fig. 2). Brain MRI showed marked cerebellar and brainstem atrophy. There was mild delayed myelination. General blood tests, screening for inborn errors of metabolism and cerebrospinal fluid analysis, resulted as normal. A genetic test confirmed SCA2, with 104 CAG repeats (normal range: from 15 to 32). SCA2 is the second most frequent SCA subtype worldwide, after SCA3. Symptoms onset usually in adulthood between 20 and 40 years. It is classically characterized by progressive cerebellar ataxia, slow saccadic eye movements, and peripheral neuropathy. The definitive diagnosis of SCA2 is based on genetic testing, when abnormal CAG trinucleotide repeat expansion of the ATXN2 gene is detected.1, 2 CAG repeat extension is unstable in intergenerational transmission, showing a tendency to further expansion over successive generations. SCA2 exhibits an inverse relationship between CAG repeat size and age of onset; this explains the marked anticipation of symptoms onset in approximately 20 years/generation.3-6 Almost all types of movement disorders may be observed in SCAs. The most frequent extrapyramidal signs observed in SCA2 include parkinsonism and dystonia.1, 2, 7, 8 However, there is no report of neonatal-onset SCA2 presenting with choreic movements and dystonia with dystonic jerks. Di Fabio et al. described a 4-month-old girl with SCA2 who presented with spontaneous dyskinetic movements.5 Additionally, choreoathetosis may be rarely observed in neonatal dentatorubral-pallidoluysian atrophy (DRPLA).9 The ocular involvement observed in SCA2 is typically characterized by severe impairment of fast eye-movement component, and saccadic system is much more compromised. Retinal involvement is classically found in SCA7 patients, but not in SCA2. Retinitis pigmentosa has been rarely described in early-onset SCA2 patients; however, to our knowledge, there is no report of SCA2 with the change in retinal pigmentation observed in our patient.3-6 In addition, seizures are typical for SCA10 and DRPLA, but not for SCA2. The few reports of SCA2 with seizures were patients with early symptoms onset.4, 6 We must bear in mind that the following SCAs may have symptoms onset at neonatal period or during the first year of life: SCA7, SCA8, SCA13, SCA27, SCA29, and DRPLA.9, 10 In conclusion, this report expands the phenotype of very-early-onset SCA2 (neonatal form) resembling a global encephalopathy, with hypotonia, choreic movements, dystonia with dystonic jerks, seizures, and retinitis. Family history of autosomal-dominant ataxia and marked cerebellar atrophy were crucial to guide the genetic test. (1) Case Report Project: A. Conception, B. Organization, C. Execution; (2) Genetic Evaluation: A. Organization, B. Execution; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. M.A.A.: 1A, 1B, 1C, 3A J.L.P.: 1B, 1C, 3A, 3B A.O.: 2A, 2B, 3B O.G.P.B.: 1B, 1C, 3A, 3B M.R.M.: 1B, 1C, 3A, 3B Funding Sources and Conflicts of Interest: This work was supported by the Italian Ministry of Health (grant no.: GR09.109; to A.O.) and the Comitato Telethon Fondazione Onlus, Italy (grant no.: GGP10121; to A.O.). The authors report no conflicts of interest. Financial Disclosures for previous 12 months: The authors report no financial disclosures. A video accompanying this article is available in the supporting information here. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.