A rare neurological condition that is primarily characterized by mild to moderate intellectual disability and dystonia of the hands. Other signs and symptoms may include dysarthria, behavioral abnormalities, recurrent seizures and/or an unusual gait (style of walking). Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe. It is caused by changes (mutations) in the ARX gene and is inherited in an X-linked recessive manner. Treatment is based on the signs and symptoms present in each person¹.

Prevalence

Limited clinical cases of predominantly European ancestry, such as Welsh/Belgian².

Age of Onset

Typical: 1-3; Range: 0-4. Mild phenotypes can make diagnosis difficult (expansions are particularly mild/absent in females)².

HPO Terms

–

Association

Mendelian

Locus

hg19 chrX:25031646-25031682

hg38 chrX:25013529-25013565

t2t chrX:24597766-24597802

Details

ARX expansions³result in a phenotypic spectrum of conditions including Partington syndrome², Early Infantile Epileptic Encephalopathy⁴, Agenesis of Corpus Callosum with Abnormal Genitalia⁵, and X-Linked Lissencephaly with Ambiguous Genitalia⁶, described in the literature^7,8.

Mechanism

LoF

Polyalanine expansions lead to reduction in protein product through unclear mechanism^9,10. Apparent aggregation and mis-localisation of mutant protein, increased with expansion length¹¹.

Detection

Because these are small coding expansions, they have been sized using targeted exon 2 PCR with fragment analysis or targeted Sanger sequencing [@pmid:11889467].

Year

2002¹²

Location in Gene

Coding Exon 2, aa 144-155

Gene Strand

Alleles

Ref. Motif

NGC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

NGC

Pathogenic (gene)

CNG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010654

2omim:309510

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

4omim:308350

5omim:300004

6omim:300215

Unraveling the pathogenesis of ARX polyalanine tract variants using a clinical and molecular interfacing approach.

Isabel,Marques, Maria João,Sá, Gabriela,Soares, Maria do Céu,Mota, Carla,Pinheiro, Lisa,Aguiar, Marta,Amado, Christina,Soares, Angelina,Calado, Patrícia,Dias, Ana Berta,Sousa, Ana Maria,Fortuna, Rosário,Santos, Katherine B,Howell, Monique M,Ryan, Richard J,Leventer, Rani,Sachdev, Rachael,Catford, Kathryn,Friend, Tessa R,Mattiske, Cheryl,Shoubridge, Paula,Jorge

Molecular genetics & genomic medicine · 2015-02-25

pmid:26029707

ARX spectrum disorders: making inroads into the molecular pathology.

Cheryl,Shoubridge, Tod,Fullston, Jozef,Gécz

Human mutation · 2010-08-01

pmid:20506206

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

POLYALANINE TRACT DISORDERS AND NEUROCOGNITIVE PHENOTYPES

Cheryl,Shoubridge, Jozef,Gecz

Madame Curie Bioscience Database [Internet] · 2013-01-01

genereviews:NBK51932

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy.

Petter,Strømme, Marie E,Mangelsdorf, Marie A,Shaw, Karen M,Lower, Suzanne M E,Lewis, Helene,Bruyere, Viggo,Lütcherath, Agi K,Gedeon, Robyn H,Wallace, Ingrid E,Scheffer, Gillian,Turner, Michael,Partington, Suzanna G M,Frints, Jean-Pierre,Fryns, Grant R,Sutherland, John C,Mulley, Jozef,Gécz

Nature genetics · 2002-03-11

pmid:11889467

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Cannabidiol attenuates epileptic phenotype and increases survival in a mouse model of developmental and epileptic encephalopathy type 1.

Lucia,Verrillo, Fabio Arturo,Iannotti, Denise,Drongitis, Katiuscia,Martinello, Loredana,Poeta, Adriano,Barra, Gaetano,Terrone, Sergio,Fucile, Vincenzo,Di Marzo, Maria Giuseppina,Miano

Epilepsia · 2025-07-03

pmid:40608247

Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina.

María Eugenia,Martín, Lenin,Intriago, Mariana,Loos, Gabriela,Reyes Valenzuela, Gabriel,Veneruzzo, María Eugenia,Foncuberta, Gabriela,Zelaya, Giovanna,Aschettino, Francisco,García, Giovanna,Flores, Roberto,Caraballo, Cristina,Alonso, Matías,Juanes

Seizure · 2025-01-31

pmid:39933386

Exploring unsolved cases of lissencephaly spectrum: integrating exome and genome sequencing for higher diagnostic yield.

Shogo,Furukawa, Mitsuhiro,Kato, Akihiko,Ishiyama, Tomohiro,Kumada, Takeshi,Yoshida, Eri,Takeshita, Pin Fee,Chong, Hideo,Yamanouchi, Yuko,Kotake, Takayoshi,Kyoda, Toshihiro,Nomura, Yohane,Miyata, Mitsuko,Nakashima, Hirotomo,Saitsu

Journal of human genetics · 2024-08-09

pmid:39123069

Clinical and genetic study of developmental and epileptic encephalopathy in Argentinean pediatric patients.

Matías,Juanes, Mariana,Loos, Gabriela,Reyes, Gabriel,Veneruzzo, Francisco Martín,García, Giovanna,Aschettino, Silvana,Calligaris, María Eugenia,Martín, María Eugenia,Foncuberta, Cristina N,Alonso, Roberto H,Caraballo

Medicina · 2022-01-01

pmid:36571524

Different types of disease-causing noncoding variants revealed by genomic and gene expression analyses in families with X-linked intellectual disability.

Michael J,Field, Raman,Kumar, Anna,Hackett, Sayaka,Kayumi, Cheryl A,Shoubridge, Lisa J,Ewans, Atma M,Ivancevic, Tracy,Dudding-Byth, Renée,Carroll, Thessa,Kroes, Alison E,Gardner, Patricia,Sullivan, Thuong T,Ha, Charles E,Schwartz, Mark J,Cowley, Marcel E,Dinger, Elizabeth E,Palmer, Louise,Christie, Marie,Shaw, Tony,Roscioli, Jozef,Gecz, Mark A,Corbett

Human mutation · 2021-05-03

pmid:33847015

Meagan S,Siehr, Cory A,Massey, Jeffrey L,Noebels

Disease models & mechanisms · 2020-03-30

pmid:32033960

ARX polyalanine expansion mutations lead to migration impediment in the rostral cortex coupled with a developmental deficit of calbindin-positive cortical GABAergic interneurons.

K,Lee, K,Ireland, M,Bleeze, C,Shoubridge

Neuroscience · 2017-06-13

pmid:28627419

Extensive phenotyping of two ARX polyalanine expansion mutation mouse models that span clinical spectrum of intellectual disability and epilepsy.

Matilda R,Jackson, Kristie,Lee, Tessa,Mattiske, Emily J,Jaehne, Ezgi,Ozturk, Bernhard T,Baune, Terence J,O'Brien, Nigel,Jones, Cheryl,Shoubridge

Neurobiology of disease · 2017-06-08

pmid:28602636

Embryonic forebrain transcriptome of mice with polyalanine expansion mutations in the ARX homeobox gene.

Tessa,Mattiske, Kristie,Lee, Jozef,Gecz, Gaelle,Friocourt, Cheryl,Shoubridge

Human molecular genetics · 2016-12-15

pmid:27798109

Locus PRTS ARX

Disease

Locus

Alleles

gnomAD

References

Additional Literature