Hereditary Chorea Research Articles

NKX2-1-conditioned disorder — «brain–lung–thyroid» syndrome: results of a multicenter study

Introduction. Brain–lung–thyroid syndrome (BLTS, choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction) is an autosomal dominant disorder associated with mutations of the NKX2-1 gene. A triad of symptoms from three organs (brain, lungs, thyroid gland) is manifested in 50% of patients, in other cases there is an incomplete phenotype of the disease. The most common manifestations are neurological. The aim of the study was to provide genetic, clinical, laboratory, and instrumental characteristics in BLTS patients with a clinical and morphological assessment of the phenotype.
 Materials and methods. Ten children from 9 families with identified mutations in the NKX2-1 gene were observed. Methods used: genealogical, Sanger sequencing, clinical and morphological assessment of the phenotype, examination of thyroid hormone levels, CT, MRI of the brain, CT of the chest, lung biopsy.
 Results. The article presents the results of molecular genetic analysis, family history, age of manifestation and diagnosis. 9 out of 10 children had damage to the central nervous system, thyroid gland, lungs, and one child had a combination of neurological pathology and hypothyroidism. Neurological pathology was represented by benign hereditary chorea (2 children), delayed motor development (8), muscular hypotension (7), ataxia (5), choreoathetosis (1), clonuses (1), seizures (1), hyperkinesis (3); respiratory — respiratory distress syndrome (RDS) of newborns (6), chronic respiratory failure (5), interstitial lung disease (6), bronchial asthma (1), chronic pneumonitis of infants (1), bronchiectasis (1). There are presented changes in computed tomograms of the lungs and during preforming CT, MRI of the brain. Typical developmental microanomalia included a protruding forehead, a wide tip of the nose, elongated narrow palpebral fissure, deep-set eyes, hypertelorism of the eyes, large rotated low-lying auricles, conical fingers.
 Conclusion. A combination of congenital hypothyroidism, neonatal RDS, heart disease, neurological disorders (hypotension, ataxia, delayed motor development, chorea), craniofacial dysmorphia is the basis for a molecular genetic examination to exclude BLTS.

The First Indian Patient With Benign Hereditary Chorea due to a De Novo Mutation in the NKX2-1 Gene.

The First Indian Patient With Benign Hereditary Chorea due to a De Novo Mutation in the NKX2-1 Gene.

Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders

ObjectiveTo perform a screening for Huntington disease (HD) phenocopies in a Swedish cohort. MethodsSeventy-three DNA samples negative for HD were assessed at a tertiary center in Stockholm. The screening included analyses for C9orf72-frontotemporal dementia/amyotrophic lateral sclerosis (C9orf72-FTD/ALS), octapeptide repeat insertions (OPRIs) in PRNP associated with inherited prion diseases (IPD), Huntington's disease-like 2 (HDL2), spinocerebellar ataxia-2 (SCA2), spinocerebellar ataxia 3 (SCA3) and spinocerebellar ataxia-17 (SCA17). Targeted genetic analysis was carried out in two cases based on the salient phenotypic features. ResultsThe screening identified two patients with SCA17, one patient with IPD associated with 5-OPRI but none with nucleotide expansions in C9orf72 or for HDL2, SCA2 or SCA3. Furthermore, SGCE-myoclonic-dystonia 11 (SGCE-M-D) and benign hereditary chorea (BHC) was diagnosed in two sporadic cases. WES identified VUS in STUB1 in two patients with predominant cerebellar ataxia. ConclusionsOur results are in keeping with previous screenings and suggest that other genes yet to be discovered are involved in the etiology of HD phenocopies.

Síndrome cérebro-pulmão-tireoide: tratamento e prognóstico com o uso de cloridrato de metilfenidato

INTRODUCTION: The “brain-lung-thyroid syndrome” is caused by mutations in the NKX2-1 gene, which encodes the thyroid transcription factor 1, and is characterized by widely diverse clinical manifestations: choreic movements, respiratory disorders and hypothyroidism. CASE REPORT: Male patient, 10 years old, son of non-consanguineous parents, being treated for subclinical hypothyroidism with levothyroxine, was referred at 4 years of age for investigation of hypotonia. There were no reports of breathing problems at birth. Investigation for hypotonia (central and neuromuscular) including muscle biopsy was normal. There was a progressive improvement in hypotonia, but the patient developed choreic movements. In view of the new clinical finding, a genetic-molecular study was carried out directed towards the NKX2-1 gene, confirming the diagnosis of “brain-lung-thyroid syndrome”. The patient started treatment with methylphenidate hydrochloride with evident improvement in choreic movements. DISCUSSION: Manifestations related to the NKX2-1 gene may include hereditary benign chorea (HBC), congenital hypothyroidism and neonatal respiratory disorders. Generally, chorea begins in early childhood, in the patient’s first year of life (most common), in later childhood or even adolescence, and progresses into the second decade after which it remains static or (rarely) resolves. Recently, the use of methylphenidate in patients with a mutation in this gene proved to be a possible therapeutic approach to control choreic movements and improve motor coordination in patients affected by this rare disease.

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing. All four patients in the two families displayed a classic BHC phenotype. The targeted pituitary MR imaging demonstrated abnormal pituitary sella morphology. Genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients. The presence of the abnormal pituitary sella in two affected members of the same family supports the hypothesis that this sign is a distinct feature of the BHC phenotype spectrum due to mutations in the TITF1 gene. Interestingly, these abnormalities seem to develop in adult life and are progressive. They occur in at least 26% of patients affected with Brain-lung-thyroid syndrome. As a part of the management of these patients we recommend to perform follow-up MRI brain with dedicated pituitary imaging also in adult life as the abnormality can occur years after the onset of chorea.

Overview on Neurological Manifestations of Thyroid Disease

Hypothyroidism and hyperthyroidism are both prevalent medical conditions that are frequently accompanied with neurologic and neuromuscular dysfunction. Triiodothyronine (T3) and thyroxine (T4) hormones are produced by the thyroid gland and play a crucial role in tissue formation and metabolism. Both of these hormones have a variety of impacts on the brain and neuromuscular system. Specially in children, because brain development can be effected by any disturbances in Thyroidal hormones level. And thus, conditions like Allan-Herndon-Dudley Syndrome & Benign Hereditary Chorea is considered genetic thyroidal diseases both will be discussed in this review. hypothyroidism can have serious consequences for neuropsychiatric function. The pathophysiological processes underlying the neurological symptoms of hypothyroidism and hyperthyroidism are likely to be multifactorial, in this review we will be looking at multiple neurological as well as psychiatric manifestations related to thyroidal hormones disorders.
 Methods: We used the phrases "hypothyroidism," "hyperthyroidism," "neurological problems," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy" in a PubMed search, google scholar and google search engines. Case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials were among the papers examined. Classification of thyroidal dysfunction has been made depending on the thyroidal hormones level. The neurological consequences of congenital hypothyroidism were examined, as well as the clinical aspects of hypothyroidism and hyperthyroidism-related neuromuscular disorders, as well as other autoimmune illnesses. Hashimoto encephalopathy's evidence and pathophysiological issues were also examined.
 Conclusion: Thyroid is critical organ due to role of its thyroidal hormones, both hypothyroidism and hyperthyroidism induce some serious neurological and phycological disorders, some of which is genetic, hypothyroidism can impact the development of child and thus regular thyroidal hormones testing is recommended in children who demonstrates any signs of neurological psychiatric or cognitive disease.

Abstract #1001910: Brain-Lung-Thyroid Syndrome (BTLS) Diagnosed in an Adult and Caused by a Newly Recognized Pathogenic Variant of Thyroid Transcription Factor-1 (TTF-1)

Brain-Lung-Thyroid Syndrome (BLTS), also known as benign hereditary chorea, is a rare autosomal dominant disorder caused by mutations in the NK2 Homeobox 1 (NKX2-1; TTF-1) gene located on chromosome 14q13. The gene codes for thyroid transcription factor-1 (TTF-1) expressed in the developing brain, lung, and thyroid. The major manifestations of BLTS are generalized chorea, recurrent respiratory infections, and hypothyroidism, with the diagnosis typically made in infancy or early childhood. We present a case of BLTS diagnosed in an adult.

Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.

Mutations of theADCY5 have been identified in patients with familial dyskinesia, early-onsetautosomal dominant chorea and dystonia, and benign hereditary chorea. Most ofthe ADCY5 mutations are de novo or transmitted in an autosomal dominantfashion. Only two pedigrees are known to show autosomal recessive inheritance. We report twosiblings with severe ID, dystonic movement, and growth failure with unknownetiology. We planned a proband-parentapproach using whole exome sequencing. Homozygous mutationin exon 21 of the ADCY5 (p.R1238W) was identified in the siblings. Althoughtheir parents were heterozygous for the mutation, they were free from clinicalmanifestations. Our results furtherexpand the phenotype/genotype correlations of the ADCY5-related disorders.Mutations of ADCY5 should be considered in pediatric patients with ID andinvoluntary movement.

A Not So Benign Family Pedigree With Hereditary Chorea: A Broader Phenotypic Expression or Additional Picture?

NKX2-1 mutations have been usually associated with a non-progressive neurological disease. Recent reports revealed a vast variability regarding its clinical expressivity. Aim of this work was widening the Benign Hereditary Chorea neurological, cognitive and behavioral phenotype through the description of a child and her family pedigree. Molecular analysis focused on NKX2-1 gene revealed a novel frameshift mutation in the three-generation members described. Cognitive scales detected a relevant developmental delay, and the clinical observation and Autism Diagnostic Observation Schedule -2 administration allowed the diagnosis of autism spectrum disorder in the proband. Microarray testing, further executed to exclude a double hit contextually provoking the complex neurodevelopmental disorder, revealed the 22q11.2 Duplication Syndrome. This paper may contribute to enlarge Benign Hereditary Chorea variable expressivity and, together with other studies reported in the literature, underlines the need to reconsider the term “benign,” verifying the opportunity of more a complex diagnosis.

Is Benign Hereditary Chorea Really Benign? Brain-Lung-Thyroid Syndrome Caused by NKX2-1 Mutations.

Since its localization to the NKX2-1 gene in 2002, the phenotype of the disorder historically called "benign hereditary chorea" has been expanding beyond chorea. The phenomenology of movement disorders and other symptomatology associated with mutations in NKX2-1 were characterized after a detailed evaluation of consecutive patients evaluated in our clinic over the past 3 years. We studied 5 patients (3 females), ages 2 to 31 years, with confirmed pathogenic variants in NKX2-1. All patients exhibited chorea, gross motor delay, and gait impairment. Other symptoms included neonatal respiratory failure (n = 4), cognitive deficits (n = 3), hypothyroidism (n = 4), joint laxity (n = 2), myoclonus (n = 1), hypotonia (n = 3), and seizures (n = 1). Chorea often proved refractory to medical therapies. The phenotype associated with pathogenic variants in NKX2-1 frequently includes disabling and often medically refractory neurological and non-neurological abnormalities. We therefore suggest that the term benign hereditary chorea be abandoned in favor of its genetic designation as NKX2-1-related disorder.

Benign hereditary chorea and deletions outside NKX2-1: What's the role of MBIP?

Heterozygous point mutations or deletions of the NKX2-1 gene cause benign hereditary chorea (BHC) or a various combinations of primary hypothyroidism, respiratory distress and neurological disorders. Deletions proximal to, but not encompassing, NKX2-1 have been described in few subjects with brain-lung-thyroid syndrome. We report on a three-generation Italian family, with 6 subjects presenting BHC and harboring a genomic deletion adjacent to NKX2-1 and including the gene MBIP, recently proposed to be relevant for the pathogenesis of brain-lung-thyroid syndrome. We observed a clear reduction of NKX2-1 transcript levels in fibroblasts from our patients compared to controls; this finding suggests that MBIP deletion affects NKX2-1 expression, mimicking haploinsufficiency caused by classical NKX2-1 related mutations.

Update on chorea

Chorea is a movement disorder characterized by a continuous flow of unpredictable muscle contractions conveying a dance-like appearance. The aim of this talk is to provide an overview of new developments in the field of chorea. There is an ongoing phase 1 trial of ISIS-HTTRX, an antisense oligonucleotide aiming at reducing the expression of huntingtin in Huntington’s disease (HD). HD is the most common cause of genetic choreas. HD phenocopies are patients with the phenotype of the disease but without the genetic defect of HD. Expansion of the C9orf72 hexanucleotide is the most common cause of phenocopies among Caucasians whereas Huntington disease like-2 mutation is the leading cause in areas with significant African background. Benign hereditary chorea (BHC), the most common etiology of genetic chorea in children, is usually caused by mutations of the NKX2-1 (TITF1). There is growing recognition though that BHC phenotype can be associated with mutations of the ADCY5 gene. The usual clinical features of the later are a variable combination of facial dyskinesia, dystonia, pyramidal signs and cognitive impairment with a characteristic worsening during induction of sleep. Vascular disease remains as the most common cause of acquired chorea in adults whereas Sydenham’s chorea (SC) account for the vast majority of cases in children. There has been a steep decline of the incidence of SC even in the developing world. In contrast, several new auto-immune causes of chorea have been recently described. Anti-NMDAR encephalitis causes a complex movement disorders that can include chorea. A few patients with anti-LGI1 antibody, a condition more commonly seen in elderly people, may have chorea as part of their clinical picture.

A further case of brain-lung-thyroid syndrome with deletion proximal to NKX2-1

Brain-lung-thyroid syndrome (OMIM #610978) is associated with mutations in the NK2 homeobox 1 (NKX2-1) gene, a transcription factor important in development. 50% of patients are affected by the full triad, comprising congenital hypothyroidism, benign hereditary chorea and infant respiratory distress syndrome. Four cases have previously been reported where a patient has features consistent with brain-lung-thyroid syndrome and a chromosome 14q13 deletion adjacent to, but not disrupting, NKX2-1. We present a patient who has a phenotype consistent with brain-lung-thyroid syndrome, featuring congenital hypothyroidism and choreoathetoid movements with gross motor delay. Thyroid ultrasound showed a small-normal gland and spontaneous resolution of hypothyroidism. Array CGH revealed a de novo 14q13.2–3 deletion adjacent to but not directly involving NKX2-1. Sequencing of NKX2-1 was normal. This report highlights a further case of chromosomal deletion adjacent to NXK2-1 in a patient with a phenotype consistent with brain-lung-thyroid syndrome, and confirms that array-CGH is a useful test in the investigation of congenital hypothyroidism. Deletion of the adjacent gene MBIP in most reported cases so far may be relevant to the pathogenesis of brain-lung-thyroid syndrome. Deletion of nearby promoter or enhancer elements acting on NKX2-1 could also be an important factor. However, further work is needed to elucidate the pathogenesis of the brain-lung-thyroid phenotype in such cases.

George Huntington: a legacy of inquiry, empathy and hope.

In the 100 years since the death of George Huntington in 1916, the disorder he described as a ‘medical curiosity’ has become a focus of intense medical and scientific interest, in part because of the contribution of families in generating knowledge about this family disease. As many writers have noted, George Huntington’s own family played a crucial role in defining this illness (Harper, 2002). What has been less appreciated is that the affected families he described also played a role, in ways that George Huntington himself acknowledged. Not quite 22 years old (Fig. 1), just graduated from the College of Physicians and Surgeons in New York City, and with little clinical experience, no established medical practice, and no patients of his own with the disorder, he wrote an account in 1872 that William Osler considered one of the most succinct and accurate portraits of a disease ever written (Osler, 1893). It was not the earliest medical account of hereditary chorea but it was certainly the most complete. And for social and cultural as well as medical and scientific reasons, it played a far more important role in defining the discrete clinical entity that soon came to be known as ‘Huntington’s chorea’ and by the late 1960s, as ‘Huntington’s disease’. Despite considerable recognition during his lifetime, George Huntington remained a small town family physician but not a provincial or isolated one. He was aware that his paper had drawn the attention of the medical profession at home and abroad and that this had helped reveal the disease in many parts of the world. He was in touch with some eminent clinicians of his day, including Osler, and an invited speaker on Huntington’s chorea at medical societies such as the influential New York Neurological Society. At a time when medicine was becoming …

Case of congenital hypothyroidism related to NKX2-1

NKX2-1 is a transcription factor. Gene NKX2-1 is expressed in tissues of the thyroid gland, brain and lungs. Mutations of NKX2-1 can lead to neurological disorders, hypothyroidism, and respiratory distress syndrome. The combinations of these symptoms are known as brain-lung-thyroid syndrome. Benign hereditary chorea is the characteristic feature of this disease and the most common manifestation of it. Chorea progresses into the second decade after which it remains stable or may even spontaneously remit. Pulmonary dysfunction is the second most common manifestation of NKX2-1-related disorders. They include respiratory distress syndrome of the newborns, interstitial lung disease between ages four months and seven years and pulmonary fibrosis in older individuals. Thyroid dysfunction can present as congenital hypothyroidism or subclinical hypothyroidism in adolescents. The combination of triad of the syndrome is present in only 50% of patients. This study includes a description of patient with brain-lung-thyroid syndrome. We described the novel mutation c.628_772del in the gene NKX2-1.

Hereditary chorea - what else to consider when the Huntington's disease genetics test is negative?

Chorea, cognitive, behavioural and psychiatric disturbance occur in varying combinations in Huntington's disease (HD). This is often easy to recognise particularly in the presence of an autosomal dominant history. Whilst HD may be the most common aetiology of such a presentation, several HD phenocopies should be considered if genetic testing for HD is negative. We searched PubMed and the Cochrane Database from January 1, 1946 up to January 1, 2016, combining the search terms: 'chorea', 'Huntington's disease', 'HDL' and 'phenocopies'. HD phenocopies frequently display additional movement disorders such as myoclonus, dystonia, parkinsonism and tics. Here, we discuss the phenotypes, and investigations of HD-like disorders where the combination of progressive chorea and cognitive impairment is obvious, but HD gene test result is negative. Conditions presenting with sudden onset chorea such as vascular, infectious and autoimmune causes are not the primary focus of our discussion, but we will make a passing reference to these as some of these conditions are potentially treatable. Hereditary forms of chorea are a heterogeneous group of conditions and this number is increasing. While most of these conditions are not curable, molecular genetic testing has enabled many of these disorders to be distinguished from HD. Getting a precise diagnosis may enable patients and their families to better understand the nature of their condition.

Phenotypic insights into ADCY5-associated disease.

ABSTRACTBackgroundAdenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal‐dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations.MethodsIn 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole‐exome sequencing.ResultsFive patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile‐onset action‐induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement.ConclusionWe further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5‐associated dyskinesia may be under‐recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Apenas mais um acidente de trabalho? Relato de um caso clínico de coreia de Huntington

Introduction: Abnormal involuntary movements, also known as dyskinesias, may manifest as chorea, athetosis, tremor, myoclonus, asterixis, spasticity, dystonia and tics. Huntington disease is the most common cause of hereditary chorea and is a cause of morbidity and premature death. Relatives and others living with the patient are often the first to notice chorea in a patient. Family physicians have a special opportunity to diagnose movement disorders. Case description: We present the case of a 41 year-old married Caucasian male living in a nuclear family. He was a construction worker but had been unemployed for one year. There was no relevant previous medical history. His father died at age 56 with “Parkinson disease”, according to one family member. He was the father of two healthy 5 year-old twin boys. A relative of the patient went to the family physician in January 2014, stating that the health of the patient had changed in the past three years. He noted ‘uncoordinated and clumsy movements’ of the limbs, memory changes, and speech difficulties. These changes were similar to the abnormal movements that the patient’s father had shown. The relative also highlighted the history of a work accident he suffered in construction work in 2012, in which he a cut his right hand on a grinding wheel, with permanent loss of function. Due to the concerns of the family, the patient visited the family physician one month later. He was referred for consultation with a neurologist and Huntington disease was diagnosed as the cause of the chorea. Comment: Movement disorders are diagnosed by taking a good clinical history (including obtaining information from family members and others living with the patient) and careful physical examination. Chorea may include the inability to maintain movement during motor tasks and this may predispose to accidents, as in this case.

Huntington's Disease, Huntington's Disease Look-Alikes‎, and Benign Hereditary Chorea: What's New?

The differential diagnosis of chorea syndromes is complex. It includes inherited forms, the most common of which is autosomal dominant Huntington's disease (HD). In addition, there are disorders mimicking HD, the so-called HD-like (HDL) syndromes. Here we review main clinical, genetic, and pathophysiological characteristics of HD and the rare HD phenocopies in order to familiarize clinicians with them. Molecular studies have shown that HD phenocopies account for about 1% of suspected HD cases, most commonly due to mutations in C9orf72 (also the main cause of frontotemporal dementia and amyotrophic lateral sclerosis syndromes), TATA box-binding protein (spinocerebellar ataxia type 17 [SCA17]/HDL4), and JPH3 (HDL2). Systematic screening studies also revealed mutations in PRNP (prion disease), VPS13A (chorea-acanthocytosis), ATXN8OS-ATXN8 (SCA8), and FXN (late-onset Friedreich's Ataxia) in single cases. Further differential diagnoses to consider in patients presenting with a clinical diagnosis consistent with HD, but without the HD expansion, include dentatorubral-pallidoluysian atrophy and benign hereditary chorea (TITF1), as well as the recently described form of ADCY5-associated neurodegeneration. Lastly, biallelic mutations in RNF216 and FRRS1L have recently been reported as autosomal recessive phenocopies of HD. There is a growing list of genes associated with chorea, yet a substantial percentage of patients remain undiagnosed. It is likely that more genes will be discovered in the future and that the clinical spectrum of the described disorders will broaden.

A Video Report of Brain-Lung-Thyroid Syndrome in a Japanese Female With a Novel Frameshift Mutation of the NKX2-1 Gene.

Benign hereditary chorea is a rare autosomal-dominant disorder that is characterized by childhood-onset nonprogressive chorea and normal cognitive function. Defects in NKX2-1 on chromosome 14q13, which encodes thyroid transcription factor 1, produce a concurrent clinical manifestation of chorea, respiratory distress, and hypothyroidism known as “brain–lung–thyroid syndrome.” Here, the authors describe a video report of benign hereditary chorea in a Japanese female with a novel frameshift mutation of NKX2-1 (c.915_916insC) (p.Ala303ArgfsX132) that was initially misdiagnosed as ataxic cerebral palsy. In early infancy, especially before the appearance of chorea, benign hereditary chorea can be misdiagnosed as ataxic and dyskinetic cerebral palsy due to shared clinical features including motor delay, hypotonia, ataxic gait, and dystonia.