Patients 1 and 3 showed atypical presentations. We also found some quite unique presentations of patients with some recurrent GNAO1 variants (p.Glu246Lys and p.Arg209His). [ojrd.biomedcentral.com]

RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior [discovery.ucl.ac.uk]

Patients with GNAO1 mutations can present with a severe, progressive hyperkinetic movement disorder with prolonged life-threatening exacerbations, which are refractory to most anti-dystonic medication. [hal-amu.archives-ouvertes.fr]

Movement abnormalities were also the major presenting symptoms of patients with GNAO1 variants. The median age at MD onset was 4 years, ranging from 3 months to 8 years, as per published reports (13). [frontiersin.org]

Results: In the first patient clinically presenting symptoms of DEE the gain-of-function (GOF) (c.607G>A) variant of GNAO1 gene was identified. In this patient MDs (combination of choreathetosis and focal dystonia) co-existed with seizures. [apcz.umk.pl]

• Disability

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia).[13882][13883] The [rarediseases.org]

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia). [rarediseases.info.nih.gov]

  ORPHA:79102 Dyrk1A-Related Intellectual Disability Syndrome Failure to thrive, Hyperactivity, Small for gestational age, Motor stereotypy ORPHA:464306 Brain Malformations-Musculoskeletal Abnormalities-Facial Dysmorphism-Intellectual Disability Syndrome [mousephenotype.org]

  Some of the patients have intellectual disabilities, but many possess higher cognitive function than may be initially appreciated. [gnao1.org]

  Quality of Life and Caregiver Burden [ Time Frame: March 2019; May-Oct 2020 ] The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire attempts to understand and quantitate the quality of life of patients and caregiver [clinicaltrials.gov]

• Weakness

  Patient 4 showed weak crying and respiratory difficulty after birth, and was treated in a neonatal intensive care unit. [ojrd.biomedcentral.com]

  ORPHA:2203 Cardiogenic Shock Elevated circulating creatinine concentration, Hypoxemia ORPHA:97292 Intellectual Disability, Birk-Barel Type Tongue fasciculations, Hyperactivity, Fatigable weakness of skeletal muscles, Fatiguable weakness... [mousephenotype.org]

• Difficulty Walking

  ORPHA:171706 Epilepsy, Progressive Myoclonic, 12 Dysmetria, Anxiety, Mental deterioration, Ataxia, Depression, Difficulty walking, Attention defic... [mousephenotype.org]

• Crying

  Patient 4 showed weak crying and respiratory difficulty after birth, and was treated in a neonatal intensive care unit. [ojrd.biomedcentral.com]

• Fever

  ORPHA:2828 Yellow Fever Leukocytosis, Elevated circulating creatinine concentration, Neutrophilia, Elevated circulating c... [mousephenotype.org]

• Psychomotor Retardation

  ORPHA:2442 Infantile Neuroaxonal Dystrophy Psychomotor deterioration, Hyperactivity, Mental deterioration, Ataxia, Unsteady gait, Emotional ... [mousephenotype.org]

• Involuntary Movements

  In addition, two patients showed involuntary movements, suggesting that GNAO1 variants can cause various neurological phenotypes. [semanticscholar.org]

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia).[13882][13883] The [rarediseases.org]

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia). [rarediseases.info.nih.gov]

  Primary Outcome Measures : Chorea [ Time Frame: March 2019; May-Oct 2020 ] The Abnormal Involuntary Movement Scale (AIMS) assesses the severity of dyskinesias, as well as the overall severity, incapacitation, and the subject's level of awareness of the [clinicaltrials.gov]

  In 2016, Ananth et al. reported GNAO1 mutations in patients of neurodevelopmental disorder with involuntary movements (NEDIM; 617493) (2). [frontiersin.org]

• Chorea

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia).[13882][13883] The [rarediseases.org]

  Specific symptoms may include seizures that start early in childhood, severe intellectual disability, poor muscle tone (hypotonia), irregular muscle contractions (chorea), and involuntary movements of the face and tongue (dyskinesia). [rarediseases.info.nih.gov]

  Early-onset chorea with profound developmental problems is quite characteristic for patients with a movement-dominant phenotype. [ojrd.biomedcentral.com]

  Primary Outcome Measures : Chorea [ Time Frame: March 2019; May-Oct 2020 ] The Abnormal Involuntary Movement Scale (AIMS) assesses the severity of dyskinesias, as well as the overall severity, incapacitation, and the subject's level of awareness of the [clinicaltrials.gov]

  ORPHA:447 Infantile Neuronal Ceroid Lipofuscinosis Dysmetria, Dystonia, Myoclonic spasms, Ataxia, Unsteady gait, Spasticity, Chorea, Clumsiness, Poo... [mousephenotype.org]

• Myoclonus

  ORPHA:51890 Angelman Syndrome Atypical absence seizure, Atonic seizure, Generalized myoclonic seizure, Myoclonus, Bilateral ton... [mousephenotype.org]

  However, intermittent nonepileptic truncal myoclonus followed by focal dystonic gait was recognized at the age of 10 years. [ojrd.biomedcentral.com]

• Neonatal Hypotonia

  Developmental milestones are also delayed in most patients with GNAO1 variants and the degree of developmental delay varies from neonatal hypotonia to intellectual disability [7,8,9]. [ojrd.biomedcentral.com]

  OMIM:128230 Transient Neonatal Diabetes Mellitus Diabetic ketoacidosis, Hypothyroidism, Transient neonatal diabetes mellitus, Maternal diabetes, M... [mousephenotype.org]

• Stereotypic Hand Movements

  Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. [ojrd.biomedcentral.com]

  OMIM:603358 Severe Intellectual Disability-Progressive Postnatal Microcephaly-Midline Stereotypic Hand Movements Syndrome Impaired social interactions, Stereotypical hand wringing, Hyperkinetic movements ORPHA:397933 Lysosomal Acid Lipase Deficiency Leukopenia [mousephenotype.org]

Results: The genetic workup revealed mutations in GNAO1 for all six patients. [hal-amu.archives-ouvertes.fr]

Tetrabenazine and DBS were the most useful treatments for dyskinesia. [discovery.ucl.ac.uk]

Symptoms may be triggered by strong emotions, illness, and purposeful movements.[13883] GNAO1 encephalopathy is caused by mutations in the GNAO1 gene and inheritance is autosomal dominant.[13884][13885] Treatment aims to relieve individual symptoms and [rarediseases.org]

In the first patient early onset of DEE (2 weeks of age) with good response of seizures to vigabatrin treatment was observed, with further development of startle response from 3 years of age with paradoxical reaction to clonazepam treatment. [apcz.umk.pl]

These results, published in the journal Science Advances, give hope of a treatment that could change the lives of patients and their families. [news-medical.net]

There is no known treatment or cure for GNAO1. Attempts to manage symptoms often involve numerous medications. Most GNAO1 patients are non-verbal and wheel chair dependent. [gnao1.org]

Conclusion In complex movement disorders of unsolved etiology clinical WES can rapidly streamline pathogenic genes. We identified two novel GNAO1 mutations. [hal-amu.archives-ouvertes.fr]

OMIM:255120 Hypoadrenocorticism, Familial Adrenal insufficiency, Hypoglycemia, Adrenal hypoplasia OMIM:240200 Sporadic Adult-Onset Ataxia Of Unknown Etiology Parkinsonism, Resting tremor, Shuffling gait, Intention tremor, Akinesia, Ataxia, Abnormal vestib [mousephenotype.org]

The G-protein–cAMP pathway axis is known to play a key role in the pathophysiology of movement disorders. At cellular level, Gαo works as an inhibitor of voltage-gated Ca2+ channels and activator of inward rectifying potassium channels (7). [frontiersin.org]

Abnormal movements and low muscle tone often prevent patients from activities like holding their heads up, swallowing food without aspirating, and bringing a spoon to their mouth. Watch the 16-Minute Documentary Film [gnao1.org]

However, this glutamine is displaced in the event of a pathologic mutation: this structural distance prevents this mechanism to take place'', explains Vladimir Katanaev. [news-medical.net]

Funding This study was supported by a research program funded by the Korea Centers for Disease Control and Prevention (Grant No. 2018-ER6901-02). [ojrd.biomedcentral.com]