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Intellectual disability, autosomal dominant 11(MRD11)

MedGen UID:
481915
Concept ID:
C3280285
Disease or Syndrome
Synonym: MRD11
 
Gene (location): EPB41L1 (20q11.23)
 
Monarch Initiative: MONDO:0013658
OMIM®: 614257

Definition

Chromosome 20q11-q12 deletion syndrome is characterized by global developmental delay, poor overall growth, sometimes with severe feeding difficulties, facial dysmorphism, and distal skeletal anomalies. Some patients may have hearing impairment, retinopathy, or cardiac defects. It is a multisystemic disorder with variable features (summary by Loddo et al., 2018). [from OMIM]

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Finger clinodactyly
MedGen UID:
120550
Concept ID:
C0265610
Congenital Abnormality
Familial isolated clinodactyly of fingers is a rare, genetic, non-syndromic, congenital limb malformation disorder characterized by angulation of a digit in the radio-ulnar (coronal) plane, away from the axis of joint flexion-extension, in several members of a single family with no other associated manifestations. Deviation is usually bilateral and commonly involves the fifth finger. Affected digits present trapezoidal or delta-shaped phalanges on imaging.
Thumbs, congenital Clasped
MedGen UID:
98140
Concept ID:
C0431886
Congenital Abnormality
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
Tarsal osteovalgus
MedGen UID:
871263
Concept ID:
C4025748
Anatomical Abnormality
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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.
Atypical behavior
MedGen UID:
535345
Concept ID:
C0233514
Mental or Behavioral Dysfunction
Atypical behavior is an abnormality in a person's actions, which can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
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.
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.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.

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
Nabavi Nouri M, Zak M, Jain P, Whitney R
Pediatr Neurol 2022 Jan;126:11-19. Epub 2021 Sep 30 doi: 10.1016/j.pediatrneurol.2021.09.017. PMID: 34740132
Nguyen DB, Khirani S, Griffon L, Baujat G, Michot C, Marzin P, Rondeau S, Luscan R, Couloigner V, Pejin Z, Zerah M, Cormier-Daire V, Fauroux B
Am J Med Genet A 2021 Jul;185(7):2108-2118. Epub 2021 Apr 28 doi: 10.1002/ajmg.a.62236. PMID: 33908178

Recent clinical studies

Etiology

Montoliu-Gaya L, Alcolea D, Ashton NJ, Pegueroles J, Levin J, Bosch B, Lantero-Rodriguez J, Carmona-Iragui M, Wagemann O, Balasa M, Kac PR, Barroeta I, Lladó A, Brum WS, Videla L, Gonzalez-Ortiz F, Benejam B, Arranz Martínez JJ, Karikari TK, Nübling G, Bejanin A, Benedet AL, Blesa R, Lleó A, Blennow K, Sánchez-Valle R, Zetterberg H, Fortea J
EBioMedicine 2023 Apr;90:104547. Epub 2023 Mar 30 doi: 10.1016/j.ebiom.2023.104547. PMID: 37002988Free PMC Article
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M
Lancet Neurol 2021 Nov;20(11):930-942. doi: 10.1016/S1474-4422(21)00245-3. PMID: 34687637Free PMC Article
Lao PJ, Handen BL, Betthauser TJ, Mihaila I, Hartley SL, Cohen AD, Tudorascu DL, Bulova PD, Lopresti BJ, Tumuluru RV, Murali D, Mathis CA, Barnhart TE, Stone CK, Price JC, Devenny DA, Johnson SC, Klunk WE, Christian BT
J Alzheimers Dis 2018;61(2):631-644. doi: 10.3233/JAD-170720. PMID: 29254096Free PMC Article
Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M
Orphanet J Rare Dis 2016 Dec 7;11(1):167. doi: 10.1186/s13023-016-0542-8. PMID: 27927236Free PMC Article
Klebe S, Stevanin G, Depienne C
Rev Neurol (Paris) 2015 Jun-Jul;171(6-7):505-30. Epub 2015 May 23 doi: 10.1016/j.neurol.2015.02.017. PMID: 26008818

Diagnosis

Nabavi Nouri M, Zak M, Jain P, Whitney R
Pediatr Neurol 2022 Jan;126:11-19. Epub 2021 Sep 30 doi: 10.1016/j.pediatrneurol.2021.09.017. PMID: 34740132
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M
Lancet Neurol 2021 Nov;20(11):930-942. doi: 10.1016/S1474-4422(21)00245-3. PMID: 34687637Free PMC Article
Morlino S, Nardella G, Castellana S, Micale L, Copetti M, Fusco C, Castori M
Am J Med Genet A 2021 Mar;185(3):955-965. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62047. PMID: 33369135
Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M
Orphanet J Rare Dis 2016 Dec 7;11(1):167. doi: 10.1186/s13023-016-0542-8. PMID: 27927236Free PMC Article
Klebe S, Stevanin G, Depienne C
Rev Neurol (Paris) 2015 Jun-Jul;171(6-7):505-30. Epub 2015 May 23 doi: 10.1016/j.neurol.2015.02.017. PMID: 26008818

Therapy

Tudorascu DL, Anderson SJ, Minhas DS, Yu Z, Comer D, Lao P, Hartley S, Laymon CM, Snitz BE, Lopresti BJ, Johnson S, Price JC, Mathis CA, Aizenstein HJ, Klunk WE, Handen BL, Christian BT, Cohen AD
Neurobiol Aging 2019 Jan;73:171-176. Epub 2018 Sep 27 doi: 10.1016/j.neurobiolaging.2018.09.030. PMID: 30359879Free PMC Article
Yang L, Xu DD, Sun CJ, Wu J, Wei HY, Liu Y, Zhang MY, Luo FH
J Clin Endocrinol Metab 2018 Nov 1;103(11):3939-3944. doi: 10.1210/jc.2017-02782. PMID: 30053089
Matevosyan NR
Arch Gynecol Obstet 2016 Jan;293(1):87-99. Epub 2015 Jun 11 doi: 10.1007/s00404-015-3770-6. PMID: 26063342
Walz K, Cohen D, Neilsen PM, Foster J 2nd, Brancati F, Demir K, Fisher R, Moffat M, Verbeek NE, Bjørgo K, Lo Castro A, Curatolo P, Novelli G, Abad C, Lei C, Zhang L, Diaz-Horta O, Young JI, Callen DF, Tekin M
Hum Genet 2015 Feb;134(2):181-90. Epub 2014 Nov 21 doi: 10.1007/s00439-014-1509-2. PMID: 25413698
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622

Prognosis

Whitford W, Taylor J, Hayes I, Smith W, Snell RG, Lehnert K, Jacobsen JC
Mol Genet Genomic Med 2024 Jan;12(1):e2350. Epub 2023 Dec 26 doi: 10.1002/mgg3.2350. PMID: 38146907Free PMC Article
Mah-Som AY, Daw J, Huynh D, Wu M, Creekmore BC, Burns W, Skinner SA, Holla ØL, Smeland MF, Planes M, Uguen K, Redon S, Bierhals T, Scholz T, Denecke J, Mensah MA, Sczakiel HL, Tichy H, Verheyen S, Blatterer J, Schreiner E, Thies J, Lam C, Spaeth CG, Pena L, Ramsey K, Narayanan V, Seaver LH, Rodriguez D, Afenjar A, Burglen L, Lee EB, Chou TF, Weihl CC, Shinawi MS
Am J Hum Genet 2023 Nov 2;110(11):1959-1975. Epub 2023 Oct 25 doi: 10.1016/j.ajhg.2023.10.007. PMID: 37883978Free PMC Article
Morlino S, Nardella G, Castellana S, Micale L, Copetti M, Fusco C, Castori M
Am J Med Genet A 2021 Mar;185(3):955-965. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62047. PMID: 33369135
Chilton I, Okur V, Vitiello G, Selicorni A, Mariani M, Goldenberg A, Husson T, Campion D, Lichtenbelt KD, van Gassen K, Steinraths M, Rice J, Roeder ER, Littlejohn RO, Srour M, Sebire G, Accogli A, Héron D, Heide S, Nava C, Depienne C, Larson A, Niyazov D, Azage M, Hoganson G, Burton J, Rush ET, Jenkins JL, Saunders CJ, Thiffault I, Alaimo JT, Fleischer J, Groepper D, Gripp KW, Chung WK
Am J Med Genet A 2020 May;182(5):962-973. Epub 2020 Feb 7 doi: 10.1002/ajmg.a.61505. PMID: 32031333
Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M
Orphanet J Rare Dis 2016 Dec 7;11(1):167. doi: 10.1186/s13023-016-0542-8. PMID: 27927236Free PMC Article

Clinical prediction guides

Mah-Som AY, Daw J, Huynh D, Wu M, Creekmore BC, Burns W, Skinner SA, Holla ØL, Smeland MF, Planes M, Uguen K, Redon S, Bierhals T, Scholz T, Denecke J, Mensah MA, Sczakiel HL, Tichy H, Verheyen S, Blatterer J, Schreiner E, Thies J, Lam C, Spaeth CG, Pena L, Ramsey K, Narayanan V, Seaver LH, Rodriguez D, Afenjar A, Burglen L, Lee EB, Chou TF, Weihl CC, Shinawi MS
Am J Hum Genet 2023 Nov 2;110(11):1959-1975. Epub 2023 Oct 25 doi: 10.1016/j.ajhg.2023.10.007. PMID: 37883978Free PMC Article
Dommergues M, Candilis D, Becerra L, Thoueille E, Cohen D, Viaux-Savelon S
Orphanet J Rare Dis 2021 Apr 13;16(1):176. doi: 10.1186/s13023-021-01810-8. PMID: 33849607Free PMC Article
Chilton I, Okur V, Vitiello G, Selicorni A, Mariani M, Goldenberg A, Husson T, Campion D, Lichtenbelt KD, van Gassen K, Steinraths M, Rice J, Roeder ER, Littlejohn RO, Srour M, Sebire G, Accogli A, Héron D, Heide S, Nava C, Depienne C, Larson A, Niyazov D, Azage M, Hoganson G, Burton J, Rush ET, Jenkins JL, Saunders CJ, Thiffault I, Alaimo JT, Fleischer J, Groepper D, Gripp KW, Chung WK
Am J Med Genet A 2020 May;182(5):962-973. Epub 2020 Feb 7 doi: 10.1002/ajmg.a.61505. PMID: 32031333
Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M
Orphanet J Rare Dis 2016 Dec 7;11(1):167. doi: 10.1186/s13023-016-0542-8. PMID: 27927236Free PMC Article
Moore SW
Pediatr Surg Int 2012 Nov;28(11):1045-58. Epub 2012 Sep 23 doi: 10.1007/s00383-012-3175-6. PMID: 23001136

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