Longitudinal follow up of a boy affected by Pol III-related leukodystrophy: a detailed phenotype description

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• 作者：Roberta Battini ; Silvano Bertelloni ; Guja Astrea ; Manuela Casarano…
• 关键词：4H leukodystrophy ; POLR3B gene ; Hypomyelination ; Hypogonadotropic hypogonadism ; Growth impairment ; Panhypopituitarism ; Recombinant GH
• 刊名：BMC Medical Genetics
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：16
• 期：1
• 全文大小：2,464 KB
• 刊物主题：Human Genetics; Genetics and Population Dynamics;
• 出版者：BioMed Central
• ISSN：1471-2350

文摘

Background The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy. The classical form is characterized by the association of hypomyelination, abnormal dentition, and hypogonadotropic hypogonadism, but the recent identification of two genes (POLR3A and POLR3B) responsible for the syndrome demonstrates that these three main characteristics can be variably combined among “Pol-III (polymerase III)-related leukodystrophies.”

Case presentation We report on the clinical, neuroradiological and endocrinological follow-up of a male affected by 4H syndrome with confirmed POLR3B mutations (c.1568 T > A/p.V523E variant in exon 15 and the novel c.1988C > T/p.T663I mutation in exon 19). Spastic-ataxic gait with worsening of motor performance, progressive moderate intellectual disability and language difficulties were the main neurological findings observed. The first six years of substantial stability of the clinical and imaging features were followed by additional six years that showed a progressive worsening of motor, language and learning disabilities in relation to a progression of the cerebellar involvement. Hypogonadotropic hypogonadism and growth hormone deficiency followed by central hypocortisolism became part of the patient’s phenotype. Thyroid function resulted unaffected during follow up.