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Intellectual disability, autosomal recessive 51(MRT51)

MedGen UID:
903243
•Concept ID:
C4225220
•
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 51; MRT51
 
Gene (location): HNMT (2q22.1)
 
Monarch Initiative: MONDO:0014759
OMIM®: 616739

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the HNMT gene. [from MONDO]

Clinical features

From HPO
Intellectual disability, severe
MedGen UID:
48638
•Concept ID:
C0036857
•
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
See: Feature record | Search on this feature
Delayed speech and language development
MedGen UID:
105318
•Concept ID:
C0454644
•
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
See: Feature record | Search on this feature
Global developmental delay
MedGen UID:
107838
•Concept ID:
C0557874
•
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
See: Feature record | Search on this feature
Motor delay
MedGen UID:
381392
•Concept ID:
C1854301
•
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
See: Feature record | Search on this feature
Intellectual disability
MedGen UID:
811461
•Concept ID:
C3714756
•
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
See: Feature record | Search on this feature
Microcephaly
MedGen UID:
1644158
•Concept ID:
C4551563
•
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Clinical and genetic heterogeneity in Dubowitz syndrome: Implications for diagnosis, management and further research.
Innes AM, McInnes BL, Dyment DA
Am J Med Genet C Semin Med Genet 2018 Dec;178(4):387-397. doi: 10.1002/ajmg.c.31661. PMID: 30580484

Recent clinical studies

Etiology

Spastic paraplegia 51: phenotypic spectrum related to novel homozygous AP4E1 mutation.
Manoochehri J, Goodarzi HR, Tabei SMB
J Genet 2022;101 PMID: 36226339
Neurocognitive, adaptive, and psychosocial functioning in individuals with Robinow syndrome.
Schwartz DD, Fein RH, Carvalho CMB, Sutton VR, Mazzeu JF, Axelrad ME
Am J Med Genet A 2021 Dec;185(12):3576-3583. Epub 2020 Sep 21 doi: 10.1002/ajmg.a.61854. PMID: 32954672
WDR73 Mutations Cause Infantile Neurodegeneration and Variable Glomerular Kidney Disease.
Vodopiutz J, Seidl R, Prayer D, Khan MI, Mayr JA, Streubel B, Steiß JO, Hahn A, Csaicsich D, Castro C, Assoum M, Müller T, Wieczorek D, Mancini GM, Sadowski CE, Lévy N, Mégarbané A, Godbole K, Schanze D, Hildebrandt F, Delague V, Janecke AR, Zenker M
Hum Mutat 2015 Nov;36(11):1021-8. Epub 2015 Aug 6 doi: 10.1002/humu.22828. PMID: 26123727Free PMC Article
Smith-Lemli-Opitz syndrome: Objective assessment of facial phenotype.
Nowaczyk MJ, Tan M, Hamid JS, Allanson JE
Am J Med Genet A 2012 May;158A(5):1020-8. Epub 2012 Mar 21 doi: 10.1002/ajmg.a.35285. PMID: 22438180
Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegeneration.
Freeman K, Gregory A, Turner A, Blasco P, Hogarth P, Hayflick S
J Intellect Disabil Res 2007 Jun;51(Pt. 6):417-26. doi: 10.1111/j.1365-2788.2006.00889.x. PMID: 17493025Free PMC Article

Diagnosis

Clinical and genetic heterogeneity in Dubowitz syndrome: Implications for diagnosis, management and further research.
Innes AM, McInnes BL, Dyment DA
Am J Med Genet C Semin Med Genet 2018 Dec;178(4):387-397. doi: 10.1002/ajmg.c.31661. PMID: 30580484
Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.
Harripaul R, Vasli N, Mikhailov A, Rafiq MA, Mittal K, Windpassinger C, Sheikh TI, Noor A, Mahmood H, Downey S, Johnson M, Vleuten K, Bell L, Ilyas M, Khan FS, Khan V, Moradi M, Ayaz M, Naeem F, Heidari A, Ahmed I, Ghadami S, Agha Z, Zeinali S, Qamar R, Mozhdehipanah H, John P, Mir A, Ansar M, French L, Ayub M, Vincent JB
Mol Psychiatry 2018 Apr;23(4):973-984. Epub 2017 Apr 11 doi: 10.1038/mp.2017.60. PMID: 28397838
Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.
Yogev Y, Perez Y, Noyman I, Madegem AA, Flusser H, Shorer Z, Cohen E, Kachko L, Michaelovsky A, Birk R, Koifman A, Drabkin M, Wormser O, Halperin D, Kadir R, Birk OS
Eur J Hum Genet 2017 Aug;25(8):966-972. Epub 2017 May 10 doi: 10.1038/ejhg.2017.85. PMID: 28488683Free PMC Article
WDR73 Mutations Cause Infantile Neurodegeneration and Variable Glomerular Kidney Disease.
Vodopiutz J, Seidl R, Prayer D, Khan MI, Mayr JA, Streubel B, Steiß JO, Hahn A, Csaicsich D, Castro C, Assoum M, Müller T, Wieczorek D, Mancini GM, Sadowski CE, Lévy N, Mégarbané A, Godbole K, Schanze D, Hildebrandt F, Delague V, Janecke AR, Zenker M
Hum Mutat 2015 Nov;36(11):1021-8. Epub 2015 Aug 6 doi: 10.1002/humu.22828. PMID: 26123727Free PMC Article
Smith-Lemli-Opitz syndrome: Objective assessment of facial phenotype.
Nowaczyk MJ, Tan M, Hamid JS, Allanson JE
Am J Med Genet A 2012 May;158A(5):1020-8. Epub 2012 Mar 21 doi: 10.1002/ajmg.a.35285. PMID: 22438180

Therapy

Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking.
Liu S, Zhang Y, Deng Z, He H, Zheng X, Hong Q, Luo X
Int J Mol Sci 2023 Jun 16;24(12) doi: 10.3390/ijms241210239. PMID: 37373384Free PMC Article
Diagnosis of autism in a rare case of tyrosine hydroxylase deficiency: a case report.
Reyes ZMD, Lynch E, Henry J, De Simone LM, Sobotka SA
BMC Med Genomics 2023 Apr 11;16(1):78. doi: 10.1186/s12920-023-01510-1. PMID: 37041529Free PMC Article
Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene.
Verhoeven WMA, Egger JIM, Janssen PKC, van Haeringen A
BMJ Case Rep 2020 Dec 12;13(12) doi: 10.1136/bcr-2020-235972. PMID: 33310825Free PMC Article
Case study for the evaluation of current treatment recommendations of guanidinoacetate methyltransferase deficiency: ineffectiveness of sodium benzoate.
Mercimek-Mahmutoglu S, Salomons GS, Chan A
Pediatr Neurol 2014 Jul;51(1):133-7. Epub 2014 Feb 21 doi: 10.1016/j.pediatrneurol.2014.02.011. PMID: 24766785

Prognosis

Whole-exome sequencing confirms implication of VPS13D as a potential cause of progressive spastic ataxia.
Durand CM, Angelini C, Michaud V, Delleci C, Coupry I, Goizet C, Trimouille A
BMC Neurol 2022 Feb 12;22(1):53. doi: 10.1186/s12883-022-02553-0. PMID: 35151251Free PMC Article
Clinical and genetic heterogeneity in Dubowitz syndrome: Implications for diagnosis, management and further research.
Innes AM, McInnes BL, Dyment DA
Am J Med Genet C Semin Med Genet 2018 Dec;178(4):387-397. doi: 10.1002/ajmg.c.31661. PMID: 30580484
Intellectual disability associated with a homozygous missense mutation in THOC6.
Beaulieu CL, Huang L, Innes AM, Akimenko MA, Puffenberger EG, Schwartz C, Jerry P, Ober C, Hegele RA, McLeod DR, Schwartzentruber J; FORGE Canada Consortium, Majewski J, Bulman DE, Parboosingh JS, Boycott KM
Orphanet J Rare Dis 2013 Apr 26;8:62. doi: 10.1186/1750-1172-8-62. PMID: 23621916Free PMC Article
Protein-truncating mutations in ASPM cause variable reduction in brain size.
Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG
Am J Hum Genet 2003 Nov;73(5):1170-7. Epub 2003 Oct 21 doi: 10.1086/379085. PMID: 14574646Free PMC Article
A review of the literature of Bardet-Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty.
Iannello S, Bosco P, Cavaleri A, Camuto M, Milazzo P, Belfiore F
Obes Rev 2002 May;3(2):123-35. doi: 10.1046/j.1467-789x.2002.00055.x. PMID: 12120419

Clinical prediction guides

Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.
Yogev Y, Perez Y, Noyman I, Madegem AA, Flusser H, Shorer Z, Cohen E, Kachko L, Michaelovsky A, Birk R, Koifman A, Drabkin M, Wormser O, Halperin D, Kadir R, Birk OS
Eur J Hum Genet 2017 Aug;25(8):966-972. Epub 2017 May 10 doi: 10.1038/ejhg.2017.85. PMID: 28488683Free PMC Article
Intellectual disability associated with a homozygous missense mutation in THOC6.
Beaulieu CL, Huang L, Innes AM, Akimenko MA, Puffenberger EG, Schwartz C, Jerry P, Ober C, Hegele RA, McLeod DR, Schwartzentruber J; FORGE Canada Consortium, Majewski J, Bulman DE, Parboosingh JS, Boycott KM
Orphanet J Rare Dis 2013 Apr 26;8:62. doi: 10.1186/1750-1172-8-62. PMID: 23621916Free PMC Article
Smith-Lemli-Opitz syndrome: Objective assessment of facial phenotype.
Nowaczyk MJ, Tan M, Hamid JS, Allanson JE
Am J Med Genet A 2012 May;158A(5):1020-8. Epub 2012 Mar 21 doi: 10.1002/ajmg.a.35285. PMID: 22438180
Protein-truncating mutations in ASPM cause variable reduction in brain size.
Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG
Am J Hum Genet 2003 Nov;73(5):1170-7. Epub 2003 Oct 21 doi: 10.1086/379085. PMID: 14574646Free PMC Article
Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.
Meinecke P, Passarge E
J Med Genet 1991 Nov;28(11):795-800. doi: 10.1136/jmg.28.11.795. PMID: 1770539Free PMC Article

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