RETT SYNDROME AND RELATED DISORDERS PANEL

Scientific Background

Classic Rett syndrome is an X-linked dominant neurodegenerative disease (frequency 1:10,000) that occurs predominantly in females. In the classic course, children develop normally until between the age of 6 and 18 months, after which time they lose acquired abilities, especially meaningful hand functions, linguistic skills and social interaction. The development of stereotypical hand movements is a leading symptom. Other symptoms are delayed growth, microcephaly, gait ataxia, episodes of apnea or hyperpnea, sleep disturbances, increasing scoliosis and seizures. The few male patients predominantly show severe neonatal encephalopathy. Classic Rett syndrome is caused by pathogenic variants in the MECP2 gene. Non-classical, atypical forms of Rett syndrome with early-onset seizures may be caused by pathogenic variants in the CDKL5 gene.

Pathogenic variants in the FOXG1 gene have been described in both classic and atypical forms of Rett syndrome and show a very high clinical heterogeneity. In recent years, several other genes have been discovered in which pathogenic variants have been described that can lead to Rett syndrome-like clinical pictures or disease courses. In patients with Rett syndrome-like diseases, NGS panel diagnostics may therefore be recommended. In individual cases, this can lead to a diagnosis and thus to more precise statements on the prognosis and the risk of recurrence.

References

Schonewolf-Greulich et al. 2019 Clin Genet 95:221 / Vidal et al. 2019 Eur J Paediatr Neurol / Allou et al. 2016, Clin Genet 91:431 / Le Meur et al. 2010, J Med Genet 47:22 / Tran Mau-Them et al. 2014, Eur J Hum Genet 22:289 / Olson et al. 2015, Am J Med Genet A 167:2017

See also: Pitt-Hopkins syndrome