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Intellectual disability

Gene: FTO

Amber List (moderate evidence)
FTO (FTO, alpha-ketoglutarate dependent dioxygenase)
EnsemblGeneIds (GRCh38): ENSG00000140718
EnsemblGeneIds (GRCh37): ENSG00000140718
OMIM: 610966, Gene2Phenotype
FTO is in 6 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 5 unrelated probands reported in literature with homozygous FTO missense variants and a syndromic presentation of growth retardation, developmental delay, facial dysmorphism, and multiple congenital anomalies. Severe developmental delay was reported in all cases. Hence, this gene can now be promoted to Green for Intellectual disability.
Created: 26 Oct 2026, 10:37 a.m. | Last Modified: 26 Oct 2026, 10:37 a.m.
Panel Version: 11.57
PMID: 37529081 Mayman et al., 2023
Case report: female proband homozygous for FTO c.287G>C, p.Arg96Pro.16 months old at time of report. She had numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function, including severe developmental delay. Fetally detected anomalies included polyhydramnios, IUGR (estimated fetal weight <1%), brain anomalies (poor gyral development, small cerebral hemispheres, and Dandy-Walker spectrum anomaly with incompletely rotated vermis, large foramen of Magendie, large cisterna magna, and hydrocephalus), musculoskeletal anomalies (all long bones <5% mean for gestational age without evidence of fracture, thoracic cage 9% mean for gestational age, and disorganized anterior maxillary tooth buds), and cardiovascular (ventricular septal defect, hypoplastic mitral valve, and aortic arch).

PMID: 26697951 Rohena et al., 2016
Report of a homozygous FTO c.965G>A, p.R322Q variant associated with a lethal malformation syndrome in a consanguineous Yemeni family. The 2 affected sibs (male and female) presented with poor growth, microcephaly (<3rd percentile), and cardiac anomalies. Cranial CT of proband A showed severe ventriculomegaly and cerebral atrophy. He also had profound GDD, craniosynostosis, bilateral cataracts, cryptorchidism, micrognathia, and other annomalies.
Proband B, his younger sister, had dysmorphic facial features, clinodactyly, mild clubfeet, and truncal hypotonia with mild spasticity. Both individuals died due to respiratory failure, at 6 and 2.5 years old.
Exome seq also detected a homozygous VUS TRIM37 variant in proband B (TRIM37 is associated with AR growth disorder with prenatal onset, including occasional progressive cardiomyopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms tumor - authors note these characteristic features were not present in the siblings).

PMID: 26740239 Çağlayan et al., 2016
Report of a female patient with a homozygous missense mutation in FTO (c.812A>C, p.His271Pro) and a homozygous nonsense mutation p.Arg403X in CETP. No CNVs. Method: WES. CETP is associated with AD Hyperalphalipoproteinemia in OMIM (143470). Parents are second cousins.
Proband presented with microcephaly (head circumference was 41 cm (<2nd percentile) and 9 months old and 47cm (<3rd percentile) at 5 yrs 5 mo), developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia, bilateral hearing loss, and other various phenotypic abnormalities. She had low LDL cholesterol and high HDL cholesterol; diagnosed with CETP-related hyperalphalipoproteinemia.
Western blot analysis demonstrated no changes in patient FTO. Q-PCR analysis revealed slightly decreased levels of FTO expression in patient cells compared to controls.

PMID: 26378117 Daoud et al., 2016
Report of a 21-month-old female with growth retardation and developmental delay, harbouring a homozygous mutation in FTO: p.(Arg316Gln). She presented with distinctive facial features, failure to thrive, global developmental delay, left ventricular cardiac hypertrophy, reduced vision and bilateral hearing loss. Seq method: Targeted NGS panels of 4000+ genes.

PMID: 19559399 Boissel et al. 2009
Report of a consanguineous Palestinian Arab family in which 9 individuals had a severe multiple congenital anomaly syndrome with death by age 3 years. Clinical features dysmorphic facial features, retrognathia, severe failure to thrive in infancy, IUGR (3/9), heart defects (6/9: VSD, AVD, PDA, 4 had hypertrophic cardiomyopathy), severe developmental delay (9/9), microcephaly, lissencephaly, seizures, Dandy-Walker malformation, and other more variable features. Affected individuals were homozygous for FTO:c.947G>A, p.Arg316Gln. Method: autozygosity mapping + targeted analysis of 28 genes on chromosome 16q12.

FTO is associated with AR Growth retardation, developmental delay, facial dysmorphism, OMIM:612938 (OMIM accessed 23rd Oct 2026).
Created: 23 Oct 2026, 3:36 p.m. | Last Modified: 26 Oct 2026, 10:32 a.m.
Panel Version: 11.55

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Growth retardation, developmental delay, facial dysmorphism, OMIM:612938; lethal polymalformative syndrome, Boissel type, MONDO:0013050

Publications

Created: 23 Oct 2026, 3:36 p.m.
Last Modified: 26 Oct 2026, 10:32 a.m.
Panel version: 11.57

Ellen McDonagh (Genomics England Curator)

I don't know

Possible DD gene for GROWTH RETARDATION DEVELOPMENTAL DELAY COARSE FACIES AND EARLY DEATH which includes global developmental delay. PMID: 26378117 - a homozygous missense variant in FTO was identified in a 21-month old girl who presented with global developmental delay and other phenotypes. PMID: 19559399 - a homozygous missense variant reported in affected members of a consanguineous Palestinian family with growth retardation, developmental delay and facial dysmorphism. In the list of known ID genes in Gilissen et al, 2014 PMID: 24896178.
Created: 13 Dec 2017, 9:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Growth retardation, developmental delay, facial dysmorphism 612938

Publications

Created: 13 Dec 2017, 9:46 p.m.

Panel version: Imported from Intellectual disability update Dec 2017 panel version 0.3

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GROWTH RETARDATION DEVELOPMENTAL DELAY COARSE FACIES AND EARLY DEATH

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:02 a.m.

Panel version: 0.306

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Growth retardation, developmental delay, facial dysmorphism, OMIM:612938
  • lethal polymalformative syndrome, Boissel type, MONDO:0013050
Tags
Q4_26_promote_green
OMIM
610966
Clinvar variants
Variants in FTO
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

26 Oct 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: FTO were changed from Growth retardation, developmental delay, facial dysmorphism 612938 to Growth retardation, developmental delay, facial dysmorphism, OMIM:612938; lethal polymalformative syndrome, Boissel type, MONDO:0013050

26 Oct 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: FTO were set to 19559399; 26378117

26 Oct 2026, Gel status: 2

Removed Tag, Added Tag

Ida Ertmanska (Genomics England Curator)

Tag watchlist was removed from gene: FTO. Tag Q4_26_promote_green tag was added to gene: FTO.

28 Sep 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to FTO.

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

5 Jan 2018, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

5 Jan 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene FTO was set to ['19559399', '26378117']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

FTO was added to Intellectual disabilitypanel. Source: Expert Review Red

24 Jun 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene FTO was changed to BIALLELIC, autosomal or pseudoautosomal

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

FTO was added to Intellectual disabilitypanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

FTO was added to Intellectual disabilitypanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen