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Intellectual disability, autosomal recessive 66(MRT66)

MedGen UID:
1648460
Concept ID:
C4748732
Disease or Syndrome
Synonym: Mental retardation, autosomal recessive 66
 
Gene (location): FERRY3 (12p13.32)
 
Monarch Initiative: MONDO:0032605
OMIM®: 618221

Definition

MRT66 is a nonsyndromic autosomal recessive intellectual developmental disorder with delayed speech development, neuropsychiatric symptoms, and relatively normal life span (Philips et al., 2017). [from OMIM]

Clinical features

From HPO
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Excessive shyness
MedGen UID:
20741
Concept ID:
C0037020
Social Behavior
Atypically high degree of awkwardness or apprehension experienced when approaching or being approached by others.
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.
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.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).

Professional guidelines

PubMed

Vetri L, Calì F, Saccone S, Vinci M, Chiavetta NV, Carotenuto M, Roccella M, Costanza C, Elia M
Int J Mol Sci 2024 Jan 17;25(2) doi: 10.3390/ijms25021146. PMID: 38256219Free PMC Article
Matza Porges S, Mor-Shaked H, Shaag A, Porat S, Daum H
Eur J Med Genet 2023 Oct;66(10):104825. Epub 2023 Sep 1 doi: 10.1016/j.ejmg.2023.104825. PMID: 37659595

Recent clinical studies

Etiology

Sezer A, Kayhan G, Percin FE
Eur J Med Genet 2023 Sep;66(9):104809. Epub 2023 Jul 19 doi: 10.1016/j.ejmg.2023.104809. PMID: 37474017
Bukowska-Olech E, Glista F, Dinwiddie A, Pepler A, Jamsheer A
Eur J Med Genet 2023 Jan;66(1):104668. Epub 2022 Nov 13 doi: 10.1016/j.ejmg.2022.104668. PMID: 36384198
Bardhan M, Polavarapu K, Bevinahalli NN, Veeramani PK, Anjanappa RM, Arunachal G, Shingavi L, Vengalil S, Nashi S, Chawla T, Nagabushana D, Mohan D, Horvath R, Nishino I, Atchayaram N
J Hum Genet 2021 Aug;66(8):813-823. Epub 2021 Mar 12 doi: 10.1038/s10038-021-00913-1. PMID: 33712684
Zarowski M, Vendrame M, Irons M, Kothare SV
Am J Med Genet A 2011 Jul;155A(7):1558-62. Epub 2011 May 27 doi: 10.1002/ajmg.a.34021. PMID: 21626671
Smalley SL, Asarnow RF, Spence MA
Arch Gen Psychiatry 1988 Oct;45(10):953-61. doi: 10.1001/archpsyc.1988.01800340081013. PMID: 3048227

Diagnosis

Vetri L, Calì F, Saccone S, Vinci M, Chiavetta NV, Carotenuto M, Roccella M, Costanza C, Elia M
Int J Mol Sci 2024 Jan 17;25(2) doi: 10.3390/ijms25021146. PMID: 38256219Free PMC Article
Matza Porges S, Mor-Shaked H, Shaag A, Porat S, Daum H
Eur J Med Genet 2023 Oct;66(10):104825. Epub 2023 Sep 1 doi: 10.1016/j.ejmg.2023.104825. PMID: 37659595
Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Rashvand Z, Kahrizi K, Najmabadi H, Najafipour R, Omrani MD
J Gene Med 2022 Apr;24(4):e3406. Epub 2022 Jan 31 doi: 10.1002/jgm.3406. PMID: 34967075
Saleh S, Beyyumi E, Al Kaabi A, Hertecant J, Barakat D, Al Dhaheri NS, Al-Gazali L, Al Shamsi A
Clin Genet 2021 Nov;100(5):573-600. Epub 2021 Aug 19 doi: 10.1111/cge.14044. PMID: 34374989

Therapy

Hirvasniemi A, Herrala P, Leisti J
Epilepsia 1995 Aug;36(8):792-7. doi: 10.1111/j.1528-1157.1995.tb01616.x. PMID: 7635097

Prognosis

Sezer A, Kayhan G, Percin FE
Eur J Med Genet 2023 Sep;66(9):104809. Epub 2023 Jul 19 doi: 10.1016/j.ejmg.2023.104809. PMID: 37474017
Meguid NA, Ismail MF, El-Mahdy RS, Barakat MA, El-Awady MK
Acta Biochim Pol 2014;61(2):259-63. Epub 2014 Jun 16 PMID: 24936518
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
O'Dea D, Parfrey PS, Harnett JD, Hefferton D, Cramer BC, Green J
Am J Kidney Dis 1996 Jun;27(6):776-83. doi: 10.1016/s0272-6386(96)90513-2. PMID: 8651240
Hirvasniemi A, Herrala P, Leisti J
Epilepsia 1995 Aug;36(8):792-7. doi: 10.1111/j.1528-1157.1995.tb01616.x. PMID: 7635097

Clinical prediction guides

Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Zarowski M, Vendrame M, Irons M, Kothare SV
Am J Med Genet A 2011 Jul;155A(7):1558-62. Epub 2011 May 27 doi: 10.1002/ajmg.a.34021. PMID: 21626671
Uyguner O, Kayserili H, Li Y, Karaman B, Nürnberg G, Hennies H, Becker C, Nürnberg P, Başaran S, Apak MY, Wollnik B
Clin Genet 2007 Mar;71(3):212-9. doi: 10.1111/j.1399-0004.2007.00762.x. PMID: 17309643
Castro NH, dos Santos RC, Nelson R, Beçak W, Hane B, Lindsey CJ, Lubs HA, Stevenson RE, Schwartz CE
Am J Med Genet A 2003 Apr 1;118A(1):49-51. doi: 10.1002/ajmg.a.10888. PMID: 12605440
Smalley SL, Asarnow RF, Spence MA
Arch Gen Psychiatry 1988 Oct;45(10):953-61. doi: 10.1001/archpsyc.1988.01800340081013. PMID: 3048227

Recent systematic reviews

Agopiantz M, Corbonnois P, Sorlin A, Bonnet C, Klein M, Hubert N, Pascal-Vigneron V, Jonveaux P, Cuny T, Leheup B, Weryha G
J Endocrinol Invest 2014 Jan;37(1):1-7. Epub 2014 Jan 8 doi: 10.1007/s40618-013-0001-5. PMID: 24464444

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