A Case Report Of 4H Syndrome Probably Caused By A Heterozygous Abnormality Of The POLR3A Gene With Preserved Intellectual Function (P7.327)

OBJECTIVE: To describe a patient with 4H syndrome showing an atypical clinical presentation. BACKGROUND: The 4H syndrome is a rare type of leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia, and POLR3A/B encoding the catalytic subunit of polymerase III was identified as the responsible gene. DESIGN/METHODS: Single case report. RESULTS: A 26-year-old man felt unstable gait and difficulty in going down the stairs at the age of 14. When he was first evaluated at the age of 15, he was 156 cm in height, hypotelorism was evident, and all his teeth were lacking. He had no spontaneous puberty and endocrinologic examination suggested hypogonadotropic hypogonadism. Neurological examinations revealed normal intelligence, cerebellar ataxia, nystagmus and bilateral positive Babinski signs. Nerve conduction studies were normal, whereas both median and tibial nerve somatosensory evoked potentials revealed marked delay of the central conduction from the spinal cord. Auditory brainstem responses also showed delayed central conduction. Brain MRI revealed scattered T2 hyperintensity areas along the pyramidal tract with normal corpus callosum and cerebellum. His gait progressively deteriorated, and he has become wheelchair bound, and then bedridden. Due to dysphagia and repeated episodes of aspiration pneumonia, laryngotracheal separation and gastrostomy was performed by the age of 22. Notably, he showed no deterioration of cognitive function, and graduated a high-class university at the age of 22. Recent MRI showed no essential changes except slight cerebellar atrophy. Recent reports of 4H syndrome prompted us to perform relevant genetic analyses, which revealed a missense mutation in POLR3A c3797 C>A from the mother of the patient. Another missense mutation from the father was not found. CONCLUSIONS: This patient was different from previously-reported cases of 4H syndrome in that he showed no cognitive regression. This might correspond to non-progressive MRI findings despite marked motor deterioration, the reason of which is unknown. Disclosure: Dr. Midori has nothing to disclose. Dr. Hatanaka has nothing to disclose. Dr. Kanbayashi has nothing to disclose. Dr. Ookuma has nothing to disclose. Dr. Sonoo has nothing to disclose. Dr. Saitsu has nothing to disclose. Dr. Matsumoto has nothing to disclose.