Objective: A 44 years old Puerto Rican woman develops progressive speech difficulties, and cognitive problems. Coordination, balance and gait get affected. Later experienced swallowing problems. No similar family history, no consanguinity, no neuroleptic, alcohol or drug use, no systemic illness or malignancy, no exposure to toxins, infection or trauma.

Background: Spinocerebellar ataxias cause various neurological deficits; several gene mutations have been identified (1). CCDC88C gene encodes a protein expressed in the brain and other tissues (2). Homozygous CCDC88C mutations can cause autosomic recessive non-syndromic hydrocephalus (3) whereas heterozygous mutations have been associated to late-onset spinocerebellar ataxia type 40 (SCA-40) in 2 reports (4,5) and spastic paraplegia in one report (6).

Method: Case Report: Neurological examination, laboratories, imaging and genetic testing were obtained.
General and Mental Status: diminished facial expression; slow thought process, flat affect, impaired calculations.
Cranial nerves: impaired vertical saccades; end-point nystagmus; slowed pursuit movements; decreased hearing.
Speech: dysarthria, low volume; episodes of coughing when talking
Sensory: normal
Motor: mild increased tone in the lower limbs, normal strength; postural and kinetic tremor worse left; left bradykinesia
Cerebellar: dysmetria and disdiadochokinesia worse left
Station and gait: loss of balance to either side when walking and turning; walks in tandem with mild difficulty, no wide base, impaired retropulsion, Romberg absent.
Reflexes: lower limbs hypereflexia; left corticospinal and ankle clonus.

Results: Genetic tests: ATAXIA panel: heterozygous for missense variant CCDC88C c.4430c>G.p. (ser 1477cys)
Negative Huntington test
Negative laboratories: 24 hours urine collection for copper and porphibilinogen, serum copper and porphyrin, anti-GAD antibodies, HIV, RPR, HTLV-1, ACE, ANA, ANTI–Ro, Anti-La.
No acanthocyes on fresh smear; normal laboratories: T3, T4 TSH, Vitamins B12, E and D, CBC, CMP, CPK
Brain MRI: mild cortical volume loss; DatScan: normal
Cervical MRI: discogenic disease C4-C5, C5-C6.
Neuropsychological test: cognitive impairment

Conclusion: A Puerto Rican woman with late onset ataxia at age 38 and no known family history is described who is heterozygous for missense variant CCDC88C that has been associated to SCA-40. This case suggests that CCDC88C gene variants should be considered in the evaluation of late-onset ataxia.

References: 1. Fahn S. Jankovic J.; Principles and Practice of Movement Disorders: Chap. 22 Ataxia: Pathophysiology and Clinical Syndromes; Churchill-Livingstone-Elsevier pp. 519-540(2007) 2. National Center for Biotechnology Information (NCBI); Genetic Testing Registry; CCDC88C coiled-coil domain containing 88C; Gene ID:440193, updated on 2-Mar-2021 3. Drielsma A., Jalas C., Simonis N, et al; Two novel CCDC88C mutations confirm the role of DAPLE in autosomal recessive congenital hydrocephalus. J Med Genet. 2012 Nov;49(11):708-12 PMID:23042809 4. Tsoi H, Yu ACS, et al; A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia; J Med Genet; 2014; 51:590-95 5. Lenska-Mieciek M, Charzewska A. et al; Familial ataxia, tremor and dementia in a Polish family with a novel mutation in the CCDC88C gene; Mov Disord 2019 Jan;34(1):142-144 PMID 30398676 6. Yahla A., Chen S. et al; A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report; BMC Neurology (2021) 21:78

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ataxia-in-a-puerto-rican-woman-with-a-missense-variant-in-the-ccdc88-gene/