Troyer syndrome: a combination of central brain abnormality and motor neuron disease?

Abstract

Hereditary spastic paraplegia is a group of clinically and genetically heterogeneous disorders consisting of pure and complicated forms. A variant with the additional features of severe atrophy of the small hand muscles, dysarthria, mental retardation, and short stature has been termed Troyer syndrome (MIM#275900) after the name of Old Order Amish families suffering from these symptoms. We report here an Austrian family with two individuals who exhibit all the features of Troyer syndrome, and provide additional data on this disorder. Electrophysiological studies showed chronic denervation and reduced motor nerve conduction velocities but normal sensory potentials. Muscle biopsy revealed a neurogenic pattern while the sural nerve was normal on histological examination. Brain abnormalities on magnetic resonance imaging consisted of a thin corpus callosum with a poorly developed cingulate gyrus and mild periventricular signal hyperintensities. These findings characterize the Troyer syndrome as a disorder of the first and second motor neuron with additional damage in the brain. The morphological features observed in this family may contribute to the grouping and subsequent understanding of complicated forms of hereditary spastic paraplegia, together with similar observations in other, more recently reported families.

Troyer syndrome revisited

“…Subtle changes seen in one on EMG could be compatible with denervation due to anterior horn cell degeneration, although further studies including muscle biopsy are needed to clarify this point.A Kuwaiti family reported as Troyer syndrome (but with no abnormalities apparent before the age of 7 years) had normal nerve conduction velocities and EMG [12]. An Austrian family reported as Troyer syndrome had chronic denervation and reduced nerve conduction velocities [1]. Sequencing of SPG20 in both of these families by us revealed no mutations (unpublished data), confirming a different genetic aetiology, as suspected.…”

“…There are, however, a number of reports of white matter abnormalities, particularly in complicated cases. Periventricular white matter abnormalities and a thin corpus callosum were reported in the Austrian Troyer-like family [1] and in two siblings who had several features in common with Troyer syndrome, but no bulbar problems [18]. Hyperintensity of the posterior limbs of the internal capsules was very recently reported in infantile ascending hereditary spastic paralysis (IAHSP) caused by alsin mutations, a form of amyotrophic lateral sclerosis which has similarities to HSP [17].…”

“…There were 20 known cases of Troyer syndrome, of which 17 were examined. There have since been several reports of similar cases around the world, although there were usually some differences from the original Troyer syndrome description [1,4,12,13,18,23]. Furthermore, as the original study predated modern imaging technologies, comparison with radiological findings reported in other populations was not possible.…”

Dwarfism in Troyer syndrome: a family with SPG20 compound heterozygous mutations and a literature review

“…With the development of genetic testing technology, Troyer syndrome has been found in a variety of ethnic populations since the first case of Troyer syndrome was reported in 1967, and new mutations in SPG20 have been detected. Through May 1, 2019, 69 cases of Troyer syndrome from 24 families have been reported globally, including 67 cases with available clinical data and 62 cases with a clear genetic diagnosis …”

SPG20 mutation in three siblings with familial hereditary spastic paraplegia

“…Only a few patients with suspected Troyer syndrome were subsequently reported in other populations (Cross and McKusick 1967; Farah et al 1997; Bertini et al 1998; Auer-Grumbach et al 1999). …”