RDP (OMIM #128235), which was first reported by Dobyns in 1993 , has been linked to various mutations in the ATP1A3 [1, 3], which encodes the α3 subunit of the Na+/K+ −ATPase. The Na+/K+ −ATPase (sodium pump), which pumps three molecules of Na + out of and two molecules of K+ into cells, is highly expressed in the basal ganglia, cerebellum, thalamic nuclei, hippocampus and several areas of the pons  and plays an important role in maintaining the electrochemical gradient at the plasma membrane prior to depolarization . ATP1A3 gene has been involved in five clinical neurological entities : (1) RDP; (2) alternating hemiplegia of childhood (AHC); (3) CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss) syndrome; (4) early infantile epileptic encephalopathy; and (5) Relapsing encephalopathy with cerebellar ataxia (RECA).
To date, 12 missense mutations, two 3-bp deletions and one 3-bp insertion in the ATP1A3 gene have been reported to be associated with RDP [4, 9]. The patient we presented had the E277K mutation, which has been previously reported in three individuals with adult-onset RDP [1, 3, 10]. RDP-associated ATP1A3 mutations are inherited in an autosomal dominant fashion but also frequently occur de novo [3, 4, 11]. We could not determine whether the patient’s mutation appeared de novo because the patient’s mother was deceased. However, there was no family history of dystonia or Parkinson disease, suggesting that our patient is likely a sporadic case.
Our patient displayed prominent lower lip inversion, a symptom that has not been described in previously reported RDP cases and was probably caused by the orofacial dystonia [3, 4, 10]. The patient had severe bulbar symptoms (dysarthria and dysphagia) and mild dystonia in her right arm and leg, consistent with the rostrocaudal gradient and asymmetric involvement of symptoms (face > arm > leg) in RDP [1, 3, 4].
About 13 reported RDP cases showed brisk reflexes on physical exammination, with only 2 cases performed ankle clonus simultaneously, but none of them exhibited the Babinski sign [5, 10, 12–16]. Although both the brisks reflexes and the ankle clonus exhibited in several RDP cases, scarce articles have discussed the pyramidal tract dysfunction in RDP . However, Oblak et al.  reported neuropathological investigations in 4 siblings with RDP and described the involvement of corticospinal tract in RDP. Also, recent DTI studies have suggested that altered microstructural integrity of brainstem pathways and adverse interactions between the cerebellum and basal ganglia may contribute to the development of idiopathic early-onset dystonia [17, 18]. Our patient exhibited both ankle clonus and a positive Babinski sign, which were caused by impairment of the pyramidal tract. DTI in our patient revealed decreased white matter integrity of the corticospinal tract in the frontal lobe and subpontine plane, providing evidence of pyramidal tract impairment.
The pyramidal tract impairment in the patient needs to be differentiated from hereditary spastic paraplegia (HSP). In the diagnosis of our patient, we realized the pyramidal tract impairment and the dystonia in our patient at first, which indicates the probable diagnosis of HSP. As complicated HSP could encompass the parapyramidal signs (including dystonia), for example in SPG21,SPG35,SPG56 [19, 20], so we take the next-gene sequencing on HSP. And the gene test of HSP was negative, which excluded SPG1-39,SPG41-56,SPG61-74,SCA5,SCA7-16,SCA19,SCA22-23, SCA26-28, SCA34-36 and so on (see in Additional file 1).
However, approximately 4 months after the diagnosis was made and a treatment with baclofen and trihexyphenidyl was started, and when our patient was re-admitted to our clinic, she not only got better in drooling and walking, but also could speak single syllable. But the psychiary symptoms, such as anxiety, depression, were much worse. She even had violent behaviours sometimes. On neurological examination, the ankle clonus and Babinski sign were no longer present, but the deep tendon reflexes of the legs were hyperactive. Baclofen is a GABA-B autoreceptor agonist that has been used to treat spasticity  and dystonia , and trihexyphenidyl is an anticholinergic agent that has proven effective for the symptomatic treatment of dystonia in young patients . Furthermore, Almeida GL et al. reported an 11-year-old boy with spastic diplegia cerebral palsy and found that ankle clonus and Babinski reflexes could be decreased during balofen administration . The treatment with baclofen and trihexyphenidyl could have contributed to the resolution of the ankle clonus and Babinski sign; however, the real reason is unknown.
No curative treatment for RDP is currently available [1, 3]. The trihexyphenidyl and baclofen treatment provided limited benefits to the patient. In the future, therapies aimed at the Na+/K+-ATPase pump may be effective treatments for RDP.