Longitudinal follow up of a boy affected by Pol III-related leukodystrophy: a detailed phenotype description
| Autor: | Rosa Pasquariello, Roberta Battini, Guja Astrea, Giovanni Cioni, Giampiero I. Baroncelli, Enrico Bertini, Lorena Travaglini, Manuela Casarano, Silvano Bertelloni |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Pediatrics Ataxia Recombinant GH Case Report Growth impairment Disease Biology Hypogonadotropic hypogonadism Growth hormone deficiency 4H leukodystrophy Hypomyelination Panhypopituitarism POLR3B gene Anodontia Brain Child Follow-Up Studies Humans Hypogonadism Leukoencephalopathies Magnetic Resonance Imaging Neurophysiological Monitoring Phenotype Genetics (clinical) Genetics Internal medicine Intellectual disability medicine Genetics(clinical) Leukodystrophy medicine.disease Hypodontia Endocrinology Thyroid function medicine.symptom |
| Zdroj: | BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/s12881-015-0203-0 |
| Popis: | 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. Conclusions A novel mutation in POLR3B in a patient with an analogue phenotype than those previously described but with more extensive endocrinological features, including hypogonadotropic hypogonadism, growth hormone deficiency and hypocortisolism, was described. These findings permit to better define the clinical spectrum of the disease, to direct specific genetic tests and to tailor clinical management. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink