MedGen

ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts and comprises a clinical continuum of the following three phenotypes: Infantile ascending hereditary spastic paraplegia (IAHSP), characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life, progressive weakness and spasticity of the upper limbs by age seven to eight years, and wheelchair dependence in the second decade with progression toward severe spastic tetraparesis and a pseudobulbar syndrome caused by progressive cranial nerve involvement. Juvenile primary lateral sclerosis (JPLS), characterized by upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia without dementia or cerebellar, extrapyramidal, or sensory signs. Juvenile amyotrophic lateral sclerosis (JALS or ALS2), characterized by onset between ages three and 20 years. All affected individuals show a spastic pseudobulbar syndrome (spasticity of speech and swallowing) together with spastic paraplegia. Some individuals are bedridden by age 12 to 50 years. [from GeneReviews]

ATP1A3-related neurologic disorders represent a clinical continuum in which at least three distinct phenotypes have been delineated: rapid-onset dystonia-parkinsonism (RDP); alternating hemiplegia of childhood (ACH); and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, some affected individuals have intermediate phenotypes or only a few features that do not fit well into one of these major phenotypes. RDP has been characterized by: abrupt onset of dystonia over days to weeks with parkinsonism (primarily bradykinesia and postural instability); common bulbar involvement; and absence or minimal response to an adequate trial of L-dopa therapy, with few exceptions. Often fever, physiologic stress, or alcoholic binges trigger the onset of symptoms. After their initial appearance, symptoms often stabilize with little improvement; occasionally second episodes occur with abrupt worsening of symptoms. Rarely, affected individuals have reported a more gradual onset of symptoms over weeks to months. Anxiety, depression, and seizures have been reported. Age of onset ranges from four to 55 years, although a childhood variation of RDP with onset between ages nine and 14 months has been reported. AHC is a complex neurodevelopmental syndrome most frequently manifesting in infancy or early childhood with paroxysmal episodic neurologic dysfunction including alternating hemiparesis or dystonia, quadriparesis, seizure-like episodes, and oculomotor abnormalities. Episodes can last for minutes, hours, days, or even weeks. Remission of symptoms occurs with sleep and immediately after awakening. Over time, persistent neurologic deficits including oculomotor apraxia, ataxia, choreoathetosis, dystonia, parkinsonism, and cognitive and behavioral dysfunction develop in the majority of those affected; more than 50% develop epilepsy in addition to their episodic movement disorder phenotype. CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is characterized by episodes of ataxic encephalopathy and/or weakness during and after a febrile illness. Onset is between ages six months and four years. Some acute symptoms resolve; progression of sensory losses and severity vary. [from GeneReviews]

Dystonia-24 is an autosomal dominant form of focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs (summary by Charlesworth et al., 2012). [from OMIM]

Dystonia-30 (DYT30) is an autosomal dominant neurologic disorder characterized by the onset of symptoms in the first decades of life. Patients present with oromandibular, cervical, bulbar, or upper limb dystonia, and usually show slow progression to generalized dystonia. Some patients may lose ambulation. A subset of patients may also have neurocognitive impairment, including mild intellectual disability or psychiatric manifestations (summary by Steel et al., 2020). In a review of the pathogenesis of disorders with prominent dystonia, Monfrini et al. (2021) classified DYT30 as belonging to a group of neurologic disorders termed 'HOPS-associated neurologic disorders' (HOPSANDs), which are caused by mutations in genes encoding various components of the autophagic/endolysosomal system, including VPS16. [from OMIM]

Dystonia-31 (DYT31) is an autosomal recessive progressive neurologic disorder characterized by involuntary muscle twisting movements and postural abnormalities affecting the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties. The age at onset ranges from childhood to young adulthood. There are usually no additional neurologic symptoms, although late-onset parkinsonism was reported in 1 family (summary by Zech et al., 2022). [from OMIM]

A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the arms. [from HPO]