Analysis of the Phenotypes in the Rett Networked Database

Abstract

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patients.

CDKL5 Deficiency Disorder—A Complex Epileptic Encephalopathy

“…In almost all patients, intellectual disability is indicated at a moderate or more often significant degree. Therefore, patients achieve an IQ score of no more than 40 [38]. The impairment seems to be mainly related to speech and small motor skills compared to achievements in gross motor skills [5].…”

“…The average number of attacks was two daily among all patients [8,30]. Epilepsy in CDD shows high drug resistance (84%) [38]. Frequent and intense epileptic episodes significantly affect the psychomotor and intellectual development of children, and result in epileptic encephalopathy, which has a secondary effect on the functioning and the quality of life of patients and their families [39].…”

“…However, only about 35% of examined boys can sit unsupported. Isolated cases of affected boys who were able to stand (2/18; 11%) or walk independently (1/18; 5.5%) were reported [5,8,9,20,38,40]. About 50% of the girls achieve grasping ability up to five years of age and 13% of girls achieve pincer grip at any stage.…”

“…Symbols, gestures, facial expressions, or vocalizations are the most common methods of communication used by about 65% of girls. In boys, only one in four communicated using gestures or vocalizations [2,3,5,8,9,20,38].…”

“…The probability of developing scoliosis before the age of 10 is 68.5%. Rehabilitation, orthopedic corsets and surgical treatment are used to treat scoliosis [7,30,38].…”