Childhood onset dystonia, chorea or related movement disorder

Gene: PTPN1

Green List (high evidence)

Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.

Created: 24 Mar 2026, 2:51 p.m. | Last Modified: 24 Mar 2026, 2:51 p.m.

Panel Version: 7.20

PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature

Created: 24 Mar 2026, 2:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215

Publications

• 10066179
• 39986310