Early progressive encephalopathy in boys and MECP2 mutations
P Kankirawatana1, H Leonard, C Ellaway
1Department of Pediatrics, University of Alabama at Birmingham, USA.
Insights
MECP2 gene mutations, typically linked to Rett syndrome in females, are also found in boys with progressive encephalopathy. These mutations present with symptoms like failure to thrive and respiratory issues.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of Rett syndrome, predominantly affecting females.
- While MECP2 mutations are rare in males, they have been documented in cases of severe progressive encephalopathy.
Purpose of the Study:
- To investigate the occurrence and clinical presentation of MECP2 mutations in boys with progressive encephalopathy.
- To identify key clinical features associated with MECP2 mutations in affected males.
Main Methods:
- Case review and genetic analysis of male patients presenting with progressive encephalopathy.
- Clinical data collection focusing on developmental milestones, neurological signs, and family history.
Main Results:
- The study identified four new de novo MECP2 mutations in boys, three confirmed pathogenic and one potentially pathogenic.
- Common clinical features observed in affected boys included failure to thrive, respiratory insufficiency, microcephaly, abnormal motor control, and intractable seizures.
- A significant proportion of affected boys had affected sisters, suggesting potential inheritance patterns.
Conclusions:
- MECP2 mutations should be considered in the differential diagnosis of boys with progressive encephalopathy.
- Specific clinical indicators such as respiratory insufficiency, abnormal movements or tone, and intractable seizures warrant further investigation for MECP2 mutations in males.
Abstract:
MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.
