Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

THOC6 Intellectual Disability Syndrome

Gabrielle Lemire  1 , A Micheil Innes  2 , Kym M Boycott  3
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
.
Affiliations
Free Books & Documents
Review

THOC6 Intellectual Disability Syndrome

Gabrielle Lemire et al.
Free Books & Documents

Excerpt

Clinical characteristics: THOC6 intellectual disability syndrome is associated with moderate-to-severe developmental delay or intellectual disability; nonspecific dysmorphic facial features (tall forehead, deep-set eyes, short and upslanted palpebral fissures, epicanthal folds, and long nose with low-hanging columella); microcephaly (typically 2-3 SD below the mean); teeth anomalies (dental caries, malocclusion, and supernumerary teeth); cardiac anomalies (most typically atrial and/or ventricular septal defects); prenatal ventriculomegaly and hydrocephalus; cryptorchidism in males; and renal malformations (most commonly unilateral renal agenesis). More rarely, affected individuals may have hypergonadotropic hypogonadism (in females), seizures, poor growth, feeding difficulties, hearing loss, refractive errors and/or other eye abnormalities, vertebral anomalies, micro/retrognathia, and imperforate / anteriorly placed anus.

Diagnosis/testing: The diagnosis of THOC6 intellectual disability syndrome is established in a proband with biallelic pathogenic variants in THOC6 identified by molecular genetic testing. For individuals from the Hutterite population suspected of having THOC6 intellectual disability syndrome, molecular genetic testing for the specific c.136G>A (p.Gly46Arg) founder variant can be considered.

Management: Treatment of manifestations: For those with poor weight gain, feeding therapy and consideration of a gastrostomy tube; for those with hearing loss, hearing aids may be considered; standard treatment for seizures, vision issues, dental caries/malocclusion, cardiac malformations, genital anomalies, hypergonadotropic hypogonadism, renal malformations, skeletal anomalies, and developmental delay / intellectual disability.

Surveillance: At each visit: monitor developmental progress, mobility, self-help skills, and behavior; assess for signs and symptoms of hydrocephalus or for new neurologic manifestations; measurement of growth parameters and evaluation of nutritional status; assessment of vision and eye alignment; assessment for dental caries and malocclusion. Evaluate renal function (BUN, creatinine, and urinalysis) at each visit or annually for those with anomalies of the kidney and urinary tract; annual audiology evaluation; evaluation of secondary sexual characteristics and menstrual cycles at each visit in females older than age 12 years.

Genetic counseling: THOC6 intellectual disability syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being unaffected and a carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants have been identified in an affected family member.

PubMed Disclaimer

Similar articles

  • Phelan-McDermid Syndrome-SHANK3 Related.
    Phelan K, Rogers RC, Boccuto L. Phelan K, et al. 2005 May 11 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2005 May 11 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301377 Free Books & Documents. Review.
  • Alpha-Mannosidosis.
    Ficicioglu C, Stepien KM. Ficicioglu C, et al. 2001 Oct 11 [updated 2024 Jun 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2001 Oct 11 [updated 2024 Jun 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301570 Free Books & Documents. Review.
  • TET3-Related Beck-Fahrner Syndrome.
    Fahrner JA. Fahrner JA. 2023 May 18. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2023 May 18. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 37200470 Free Books & Documents. Review.
  • NFIX-Related Malan Syndrome.
    Priolo M. Priolo M. 2024 Aug 1. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2024 Aug 1. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 39083629 Free Books & Documents. Review.
  • Myhre Syndrome.
    Lin AE, Brunetti-Pierri N, Lindsay ME, Schimmenti LA, Starr LJ. Lin AE, et al. 2017 Apr 13 [updated 2024 Dec 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2017 Apr 13 [updated 2024 Dec 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 28406602 Free Books & Documents. Review.
See all similar articles

References

    1. Accogli A, Scala M, Calcagno A, Castello R, Torella A, Musacchia F, Allegri AME, Mancardi MM, Maghnie M, Severino M, Nigro V, Capra V, et al. Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome. Am J Med Genet A. 2018;176:2835-40. - PubMed
    1. Amos JS, Huang L, Thevenon J, Kariminedjad A, Beaulieu CL, Masurel-Paulet A, Najmabadi H, Fattahi Z, Beheshtian M, Tonekaboni SH, Tang S, Helbig KL, Alcaraz W, Riviere JB, Faivre L, Innes AM, Lebel RR, Boycott KM, et al. Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping. Clin Genet. 2017;91:92-9. - PubMed
    1. Anazi S, Alshammari M, Moneis D, Abouelhoda M, Ibrahim N, Alkuraya FS. Confirming the candidacy of THOC6 in the etiology of intellectual disability. Am J Med Genet A. 2016;170A:1367-9. - PubMed
    1. Beaulieu CL, Huang L, Innes AM, Akimenko MA, Puffenberger EG, Schwartz C, Jerry P, Ober C, Hegele RA, Mcleod DR, Schwartzentruber J, Majewski J, Bulman DE, Parboosingh JS, Boycott KM, et al. Intellectual disability associated with a homozygous missense mutation in THOC6. Orphanet J Rare Dis. 2013;8:62. - PMC - PubMed
    1. Boycott KM, Beaulieu C, Puffenberger EG, Mcleod DR, Parboosingh JS, Innes AM. A novel autosomal recessive malformation syndrome associated with developmental delay and distinctive facies maps to 16ptel in the Hutterite population. Am J Med Genet A. 2010;152A:1349-56. - PubMed

LinkOut - more resources