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Intellectual developmental disorder, autosomal dominant 74(MRD74)

MedGen UID:
1845603
Concept ID:
C5882749
Disease or Syndrome
Synonym: MRD74
 
Gene (location): HNRNPC (14q11.2)
 
Monarch Initiative: MONDO:0958203
OMIM®: 620688

Definition

Autosomal dominant intellectual developmental disorder-74 (MRD74) is characterized by global developmental delay, including delay of gross and fine motor skills and speech delay, and variable subtle dysmorphic facial features (Niggl et al., 2023). [from OMIM]

Clinical features

From HPO
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
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
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.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Diminished ability to concentrate
MedGen UID:
65900
Concept ID:
C0235198
Finding
Being unable to focus one's attention or mental effort on a particular object or activity.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Obstructive sleep apnea syndrome
MedGen UID:
101045
Concept ID:
C0520679
Disease or Syndrome
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
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.
Motor tics
MedGen UID:
199761
Concept ID:
C0751900
Sign or Symptom
Movement-based tics affecting discrete muscle groups.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Happy demeanor
MedGen UID:
344654
Concept ID:
C1856115
Finding
A conspicuously happy disposition, characterized by frequent smiling and laughing, which may be contextually inappropriate or unrelated to the situation.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Delayed fine motor development
MedGen UID:
869257
Concept ID:
C4023681
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
Typical absence seizure
MedGen UID:
1790454
Concept ID:
C5551411
Disease or Syndrome
A typical absence seizure is a type of generalized non-motor (absence) seizure characterized by its sudden onset, interruption of ongoing activities, a blank stare, possibly a brief upward deviation of the eyes. Usually the patient will be unresponsive when spoken to. Duration is a few seconds to half a minute with very rapid recovery. Although not always available, an EEG would usually show 3 Hz generalized epileptiform discharges during the event.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
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.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

Recent clinical studies

Etiology

Wisch JK, McKay NS, Boerwinkle AH, Kennedy J, Flores S, Handen BL, Christian BT, Head E, Mapstone M, Rafii MS, O'Bryant SE, Price JC, Laymon CM, Krinsky-McHale SJ, Lai F, Rosas HD, Hartley SL, Zaman S, Lott IT, Tudorascu D, Zammit M, Brickman AM, Lee JH, Bird TD, Cohen A, Chrem P, Daniels A, Chhatwal JP, Cruchaga C, Ibanez L, Jucker M, Karch CM, Day GS, Lee JH, Levin J, Llibre-Guerra J, Li Y, Lopera F, Roh JH, Ringman JM, Supnet-Bell C, van Dyck CH, Xiong C, Wang G, Morris JC, McDade E, Bateman RJ, Benzinger TLS, Gordon BA, Ances BM; Alzheimer's Biomarker Consortium-Down syndrome; Dominantly Inherited Alzheimer Network
Lancet Neurol 2024 May;23(5):500-510. doi: 10.1016/S1474-4422(24)00084-X. PMID: 38631766Free PMC Article
Wojcik MH, Srivastava S, Agrawal PB, Balci TB, Callewaert B, Calvo PL, Carli D, Caudle M, Colaiacovo S, Cross L, Demetriou K, Drazba K, Dutra-Clarke M, Edwards M, Genetti CA, Grange DK, Hickey SE, Isidor B, Küry S, Lachman HM, Lavillaureix A, Lyons MJ, Marcelis C, Marco EJ, Martinez-Agosto JA, Nowak C, Pizzol A, Planes M, Prijoles EJ, Riberi E, Rush ET, Russell BE, Sachdev R, Schmalz B, Shears D, Stevenson DA, Wilson K, Jansen S, de Vries BBA, Curry CJ
Am J Med Genet A 2023 Jul;191(7):1900-1910. Epub 2023 May 14 doi: 10.1002/ajmg.a.63226. PMID: 37183572Free PMC Article
Tenorio-Castaño J, Morte B, Nevado J, Martinez-Glez V, Santos-Simarro F, García-Miñaúr S, Palomares-Bralo M, Pacio-Míguez M, Gómez B, Arias P, Alcochea A, Carrión J, Arias P, Almoguera B, López-Grondona F, Lorda-Sanchez I, Galán-Gómez E, Valenzuela I, Méndez Perez MP, Cuscó I, Barros F, Pié J, Ramos S, Ramos FJ, Kuechler A, Tizzano E, Ayuso C, Kaiser FJ, Pérez-Jurado LA, Carracedo Á, The ENoD-Ciberer Consortium, The Side Consortium, Lapunzina P
Genes (Basel) 2021 May 13;12(5) doi: 10.3390/genes12050738. PMID: 34068396Free PMC Article
Amudhavalli SM, Hanson R, Angle B, Bontempo K, Gripp KW
Am J Med Genet A 2018 Jul;176(7):1648-1656. doi: 10.1002/ajmg.a.38832. PMID: 30160832
McDonald CM, Johnson ER, Abresch RT, Carter GT, Fowler WM Jr, Kilmer DD
Am J Phys Med Rehabil 1995 Sep-Oct;74(5 Suppl):S117-30. doi: 10.1097/00002060-199509001-00006. PMID: 7576419

Diagnosis

Wojcik MH, Srivastava S, Agrawal PB, Balci TB, Callewaert B, Calvo PL, Carli D, Caudle M, Colaiacovo S, Cross L, Demetriou K, Drazba K, Dutra-Clarke M, Edwards M, Genetti CA, Grange DK, Hickey SE, Isidor B, Küry S, Lachman HM, Lavillaureix A, Lyons MJ, Marcelis C, Marco EJ, Martinez-Agosto JA, Nowak C, Pizzol A, Planes M, Prijoles EJ, Riberi E, Rush ET, Russell BE, Sachdev R, Schmalz B, Shears D, Stevenson DA, Wilson K, Jansen S, de Vries BBA, Curry CJ
Am J Med Genet A 2023 Jul;191(7):1900-1910. Epub 2023 May 14 doi: 10.1002/ajmg.a.63226. PMID: 37183572Free PMC Article
Nogueira M, Melo C, Grangeia A, Magalhães T, Soares C, Dias R, Fonseca J, Sampaio M, Sousa R
Rev Neurol 2022 Mar 1;74(5):170-173. doi: 10.33588/rn.7405.2021068. PMID: 35211951
Schlögel MJ, Mendola A, Fastré E, Vasudevan P, Devriendt K, de Ravel TJ, Van Esch H, Casteels I, Arroyo Carrera I, Cristofoli F, Fieggen K, Jones K, Lipson M, Balikova I, Singer A, Soller M, Mercedes Villanueva M, Revencu N, Boon LM, Brouillard P, Vikkula M
Orphanet J Rare Dis 2015 May 2;10:52. doi: 10.1186/s13023-015-0271-4. PMID: 25934493Free PMC Article
Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article
McDonald CM, Johnson ER, Abresch RT, Carter GT, Fowler WM Jr, Kilmer DD
Am J Phys Med Rehabil 1995 Sep-Oct;74(5 Suppl):S117-30. doi: 10.1097/00002060-199509001-00006. PMID: 7576419

Therapy

Amudhavalli SM, Hanson R, Angle B, Bontempo K, Gripp KW
Am J Med Genet A 2018 Jul;176(7):1648-1656. doi: 10.1002/ajmg.a.38832. PMID: 30160832
Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article

Prognosis

Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article
Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ
Am J Med Genet A 2011 Jul;155A(7):1511-6. Epub 2011 Jun 10 doi: 10.1002/ajmg.a.34074. PMID: 21671394Free PMC Article
Niida Y, Lawrence-Smith N, Banwell A, Hammer E, Lewis J, Beauchamp RL, Sims K, Ramesh V, Ozelius L
Hum Mutat 1999;14(5):412-22. doi: 10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K. PMID: 10533067

Clinical prediction guides

Wisch JK, McKay NS, Boerwinkle AH, Kennedy J, Flores S, Handen BL, Christian BT, Head E, Mapstone M, Rafii MS, O'Bryant SE, Price JC, Laymon CM, Krinsky-McHale SJ, Lai F, Rosas HD, Hartley SL, Zaman S, Lott IT, Tudorascu D, Zammit M, Brickman AM, Lee JH, Bird TD, Cohen A, Chrem P, Daniels A, Chhatwal JP, Cruchaga C, Ibanez L, Jucker M, Karch CM, Day GS, Lee JH, Levin J, Llibre-Guerra J, Li Y, Lopera F, Roh JH, Ringman JM, Supnet-Bell C, van Dyck CH, Xiong C, Wang G, Morris JC, McDade E, Bateman RJ, Benzinger TLS, Gordon BA, Ances BM; Alzheimer's Biomarker Consortium-Down syndrome; Dominantly Inherited Alzheimer Network
Lancet Neurol 2024 May;23(5):500-510. doi: 10.1016/S1474-4422(24)00084-X. PMID: 38631766Free PMC Article
Walsh S, Gösswein SS, Rump A, von der Hagen M, Hackmann K, Schröck E, Di Donato N, Kahlert AK
Eur J Med Genet 2020 Oct;63(10):104019. Epub 2020 Jul 23 doi: 10.1016/j.ejmg.2020.104019. PMID: 32712214
Raykova D, Klar J, Azhar A, Khan TN, Malik NA, Iqbal M, Tariq M, Baig SM, Dahl N
PLoS One 2014;9(4):e93607. Epub 2014 Apr 8 doi: 10.1371/journal.pone.0093607. PMID: 24714551Free PMC Article
Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ
Am J Med Genet A 2011 Jul;155A(7):1511-6. Epub 2011 Jun 10 doi: 10.1002/ajmg.a.34074. PMID: 21671394Free PMC Article
Niida Y, Lawrence-Smith N, Banwell A, Hammer E, Lewis J, Beauchamp RL, Sims K, Ramesh V, Ozelius L
Hum Mutat 1999;14(5):412-22. doi: 10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K. PMID: 10533067

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