The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by ... The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005).
Ariani et al. (2008) reported 2 unrelated girls, aged 22 years and 7 years, with a congenital variant of Rett syndrome. Both had normal birth, but developed progressive microcephaly at age 3 months. Both showed poor response early ... Ariani et al. (2008) reported 2 unrelated girls, aged 22 years and 7 years, with a congenital variant of Rett syndrome. Both had normal birth, but developed progressive microcephaly at age 3 months. Both showed poor response early in life and were unable to lift their heads. Both also were apraxic and showed peculiar jerky movements of the upper limbs and midline stereotypic activities typical of classic Rett syndrome. Neither acquired spoken language, and both had EEG abnormalities with a multifocal pattern with spikes and sharp waves and occasional paroxysmal activity. Other features included corpus callosum hypoplasia, occasional abnormal breathing patterns, and bruxism. Mencarelli et al. (2010) reported 4 unrelated girls, ranging in age from 3 to 13 years, with the congenital variant of Rett syndrome. All had hypotonia, unresponsiveness, and irritability in the neonatal period. At birth, head circumference was normal, but showed deceleration of growth soon after. Psychomotor regression became apparent between 3 and 6 months of age. Motor development was severely impaired, and hand use was absent. Typical stereotypical hand and mouth movements were present. All had severe mental retardation and poor eye contact, and none achieved walking or speech. Other features included abnormal movements of the tongue, jerky movements of the limbs, and seizures. Brain MRI showed hypoplasia of the corpus callosum. The older patients had severe scoliosis, kyphosis, genu valgum, pes planus, and spasticity. Philippe et al. (2010) reported 2 unrelated females with the congenital variant of Rett syndrome. The first was a 22-year-old woman who was noted to have deceleration of head growth at age 2 months, followed by impaired social interaction consistent with autism. She later showed sleep disruption associated with EEG abnormalities, and never acquired speech or purposeful hand movements. Brain MRI showed hypoplasia of the corpus callosum with decreased white matter volume. The second patient was a 10-year-old girl who was noted to have delayed development at 6 months of age, followed by postnatal deceleration of head growth at 9 months. At age 5 years, she had repetitive stereotypic hand movements, absence of speech, and inappropriate laughter. At age 9 years, she had poor eye contact, ataxia, and drooling. Brain MRI did not reveal any malformations. Philippe et al. (2010) suggested that the second patient's phenotype could be compatible with a diagnosis of classic Rett syndrome, and suggested that individuals with classic Rett syndrome should also be tested for mutations in the FOXG1 gene. Kortum et al. (2011) reported 11 patients with what they termed the 'FOXG1 syndrome,' and reviewed the phenotype of 15 previously reported patients. The disorder comprises mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies, and dyskinesias, such as dystonia, chorea, and athetosis. The patients also developed epilepsy after age 3 months and showed poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastroesophageal reflux. Brain imaging studies showed simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachygyria. Although the phenotype overlaps both classic and congenital Rett syndrome, Kortum et al. (2011) concluded that patients with FOXG1 mutations have a distinctive and clinically recognizable phenotype consistent with a developmental encephalopathy.
In 2 unrelated girls with a congenital variant of Rett syndrome, Ariani et al. (2008) identified heterozygous truncating mutations in the FOXG1 gene (164874.0001 and 164874.0002).
Mencarelli et al. (2010) identified 4 different de novo heterozygous ... In 2 unrelated girls with a congenital variant of Rett syndrome, Ariani et al. (2008) identified heterozygous truncating mutations in the FOXG1 gene (164874.0001 and 164874.0002). Mencarelli et al. (2010) identified 4 different de novo heterozygous mutations in the FOXG1 gene (see, e.g., 164874.0003-164874.0004) in 4 unrelated girls with the congenital variant of Rett syndrome. Philippe et al. (2010) identified 2 different de novo heterozygous mutations in the FOXG1 gene (164874.0005 and 164874.0006) in 2 unrelated females with the congenital variant of Rett syndrome. Kortum et al. (2011) identified heterozygous deletions or mutations in the FOXG1 gene in 11 of 210 patients with severe mental retardation, microcephaly, and/or brain abnormalities. One known mutation (164874.0007) was identified in 2 patients, and 9 novel mutations, including 2 large deletions, a balanced translocation and a deletion that both may have disrupted/displaced putative cis-regulatory elements of FOXG1, and 5 sequence changes, were identified. All mutations that could be evaluated were of de novo origin.