Abstract Details

Title Neurodegeneration and muscular involvement in intermediate autosomal recessive CLCN7-related Osteopetrosis: an atypical presentation

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-049

Objective

To describe a rare case of osteopetrosis with atypical neurologic involvement and discuss the relationship between clinical and genetic findings.

Background Osteopetrosis is a rare disease in which osteoclastic dysfunction compromises bone reabsorption and remodelling. Clinical presentation is heterogeneous but neurological involvement is usually mild and related to compression due to abnormal bone growth.

Design/Methods

Clinical history, neurological examination, neuropsychological evaluation and diagnostic workup were retrospectively reviewed.

Results A 22-year-old man had a history of global developmental delay since he was 3 years old. At the age of 8 years, he developed behavioral changes and progressive motor impairment with initial involvement of fine motor skills, later developing axial rigidity, asymmetric bradykinesia and dystonic posturing in the left hand. He also developed generalized muscle hypertrophy with episodic pain. Elevated creatine kinase and increased bone density in radiographs led to the suspicion of osteopetrosis, later supported by genetic testing revealing a probably pathogenic homozygous mutation in the CLCN7 gene (c.1798-14C>A). Brain MRI revealed global cerebral and cerebellar atrophy with typical cranial bone involvement, without nerve compression or basal ganglia calcification. Diagnostic workup was negative for causes of secondary parkinsonism. Currently, the patient maintains a severe progression of extrapyramidal symptoms with significant motor impairment and no response to levodopa. A recent neuropsychological evaluation revealed a global cognitive deficit with marked psychomotor latency and comprehension deficit, preservation of temporospatial orientation, visual memory, naming, non-verbal reasoning and visuospatial abilities (despite graphomotor impairment).

Conclusions An association between bone disease and neurodegeneration was described in other entities, like Nasu-Hakola disease. Although extrapyramidal symptoms with basal ganglia calcification were reported in a patient with osteopetrosis, severe extrapyramidal symptoms are very rare and muscle hypertrophy has never been described in this disease. Therefore, possible pathological mechanisms associated with this atypical clinical presentation should be discussed.

Authors/Disclosures
Joao L. Durães, MD (Hospitais Da Universidade De Coimbra) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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