Perrault syndrome is a genetically heterogenous, very rare disease, characterized
clinically by sensorineural hearing loss, ovarian dysfunction and neurological symptoms.
We present the case of a 33 years old female patient with TWNK-associated Perrault
syndrome. The TWNK gene is coding the mitochondrial protein Twinkle and currently
there are only two reports characterizing the phenotype of TWNK-associated Perrault
syndrome. None of these publications reported about special brain MRI alterations
and neuropathological changes in the muscle and peripheral nerves.Our patients with
TWNK-dependent Perrault syndrome had severe bilateral hypoacusis, severe ataxia, polyneuropathy,
lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis. Psychiatric
symptoms such as depression and paranoia were present as well. Brain MRI observed
progressive cerebellar hyperintensive signs associated with cerebellar, medulla oblongata
and cervical spinal cord atrophy. Light microscopy of the muscle biopsy detected severe
neurogenic lesions. COX staining was centrally reduced in many muscle fibers. Both
muscle and sural nerve electron microscopy detected slightly enlarged mitochondria
with abnormal cristae surrounded by lipid vacuoles. In the sural nerve, dystrophic
axons had focally uncompacted myelin lamellae present. Genetic investigation revealed
multiple mtDNA deletion and compound heterozygous mutations of the TWNK gene (c.1196
A > G, c.1358 G > A).This study demonstrates that TWNK associated Perrault syndrome
has a much broader phenotype as originally published. The coexistence of severe hypoacusis,
spastic limb weakness, ataxia, polyneuropathy, gonadal dysgensia, hyperintense signals
in the cerebellum and the presence of the mtDNA multiple deletion could indicate the
impairment of the TWNK gene. This is the first report about pyramidal tract involvement
and cerebellar MRI alteration associated with TWNK-related Perrault syndrome.
