Childhood onset dystonia, chorea or related movement disorder

Gene: ATAD1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of biallelic variants with hyperekplexia. As other hyperekplexia-causing genes (e.g. GLRA1 & GLRB) are rated green on this panel, this gene should also be rated green in the next update.

Created: 23 Apr 2026, 5:28 p.m. | Last Modified: 23 Apr 2026, 5:28 p.m.

Panel Version: 7.25

PMID:28180185 (2017) reported the identification of a homozygous nonsense variant in ATAD1 gene (p.Glu276Ter) in a large consanguineous Kuwaiti family. They presented with a neurological disorder characterised by hypertonia, seizures, and death. Detailed clinical information was available for two of the patients and they had no or little spontaneous movement. There is also functional evidence available from ATAD1 knockout mouse model, from which the authors suggested loss-of-function mechanism for the variant.

PMID:29390050 (2018) reported the identification of a homozygous frameshift variant in ATAD1 gene (p.His357Argfs*15) in three siblings from a consanguineous Tunisian family who presented with a severe, lethal encephalopathy associated with stiffness and arthrogryposis. The proband had exaggerated startle and clonic movements. Functional evidence was available which suggested that gain-of-function for the variant.

PMID:29659736 (2018) reported a female infant born of consanguineous parents with a similar disorder. She was identified with a homozygous ATAD1 variant (c.162G-C) that was predicted to result in a missense variant or a splicing defect causing loss of function. She was a stiff baby at birth and had no spontaneous movements.

PMID:33134516 (2020) reported two new unrelated patients presenting with a similar distinctive phenotype comprising congenital stiffness of limbs, absent spontaneous movements, weak sucking, and hypoventilation. They were identified with homozygous variants in ATAD1 gene (Patient 1: p.His357Argfs*15; Patient 2: p.Gly128Val).

PMID:36933275 (2023) reported the identification of two novel heterozygous variants in ATAD1 gene (maternal: c.690+1G>c - splice site variant; paternal: c.148G>T - nonsense) in a female neonate presenting with hypertonia, tremulousness and clonus.

This gene has been associated with hyperekplexia 4 in OMIM (MIM #618011, last accessed 23 April 2026), but not in Gene2Phenotype or ClinGen.
Sources: Literature

Created: 23 Apr 2026, 5:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperekplexia 4, OMIM:618011; hyperekplexia 4, MONDO:0044330

Publications

• 28180185
• 29390050
• 29659736
• 33134516
• 36933275