Posted - February 2019 in Research Highlights
Associated with joint deformities in the feet and hands
A new dominantly inherited HSP, complicated by joint deformities in the feet and hands, has been found by researchers at Vanderbilt University in the USA. Exhaustive genetic analysis failed to identify the disease-causing gene.
Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurological disorders. HSP is classified as pure when only a spastic weakness of the lower extremities is present. Complex HSP comes with additional neurological or systemic abnormalities. Complex HSP with skeletal abnormalities is rare and mostly seen in autosomal recessive HSP. Autosomal dominant (AD) complex HSP with skeletal abnormalities are consistently seen only in SPG9 (spastic gait type 9).
In this paper, we report a kindred condition with AD HSP among four living affected individuals who had progressive, adult onset spastic paraparesis that was associated with a distal arthrogryposis (DA) in every affected individual. They also had episodes of rhabdomyolysis without any clinical signs of myopathy. Exhaustive genetic analysis including targeted sequencing of known HSP and DA genes and whole exome sequencing did not identify the disease-causing gene. It excluded all known HSP and DA genes.
We propose that this is a novel genetic type of complex AD HSP. Elucidation of a genetic cause of this type of HSP will further contribute to our understanding of axonal degeneration and skeletal abnormalities.
SOURCE: Brain Sci. 2018 Jul 19;8(7). pii: E136. doi: 10.3390/brainsci8070136. PMID: 30029526
Novel Type of Complicated Autosomal Dominant Hereditary Spastic Paraplegia Associated with Congenital Distal Arthrogryposis Type 1.
1 Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected]
2 Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. [email protected]
3 George E. Wahlen Department of Veterans Administration Medical Center, Salt Lake City, UT 84148, USA. [email protected]
4 Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected]
5 Tennessee Valley Health Care System, Veterans Administration Medical Center, Nashville, TN 37212-2637, USA. [email protected]
6 Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected]