Skeletal abnormalities in Rett syndrome: increasing evidence for dysmorphogenetic defects

Area of Science:

• Medical imaging
• Genetics
• Pediatric neurology

Background:

• Rett syndrome is a complex neurodevelopmental disorder.
• Previous observations suggested potential skeletal abnormalities in individuals with Rett syndrome.
• This led to the hypothesis that Rett syndrome might be classified as a multiple congenital abnormalities/mental retardation (MCA/MR) syndrome.

Purpose of the Study:

• To investigate the prevalence of specific metatarsal and metacarpal abnormalities in Rett syndrome.
• To determine if these skeletal findings are associated with age or other factors.
• To explore the potential of these abnormalities as diagnostic markers for Rett syndrome.

Main Methods:

• Radiological examination of 17 individuals diagnosed with Rett syndrome in Western Australia.
• Assessment for short fourth and/or fifth metatarsals and metacarpals.
• Evaluation of ulnar variance and bone density in the hands.

Main Results:

• Shortening of the fourth and/or fifth metatarsals was observed in 65% of cases.
• Shortening of the fourth and/or fifth metacarpals was found in 57% of cases.
• These bone shortenings were significantly more prevalent in older girls (≥14 years). Negative ulnar variance (79%) and reduced hand bone density (86%) were also common.

Conclusions:

• The high prevalence of metatarsal and metacarpal abnormalities supports the classification of Rett syndrome within MCA/MR syndromes.
• These skeletal findings may serve as valuable morphologic markers for aiding in the diagnosis of Rett syndrome.
• Further research, including a nationwide study, is warranted to confirm these findings and investigate the underlying pathogenesis.