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

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.

Yawning frequency and distribution in preterm and near term infants assessed throughout 24-h recordings.

Yawning has been observed in foetuses and preterm infants. The aim of this study was to assess the frequency and the 24 h distribution of yawning in preterm infants. Twelve low-risk infants between 31 and 40 weeks of post-conceptional age (PCA) were continuously video-recorded for 24 h in their incubator. Spontaneous yawning was defined as opening of the mouth to its full extension in a dramatic stretch movement. The results showed that the rate of yawning across the 24-h period was 1.10/h. The highest incidence of yawns was in the waking motility pattern when compared to active sleep or quiet sleep motility patterns. Between 31 and 40 weeks, yawn incidence significantly decreased mainly during the day. The marked decrease in yawn frequency with age may be related to the development of circadian and homeostatic control of sleep and wake.