U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Intellectual disability, autosomal dominant 48(MRD48)

MedGen UID:
1619532
Concept ID:
C4540321
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 48; MENTAL RETARDATION, AUTOSOMAL DOMINANT 48
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): RAC1 (7p22.1)
 
Monarch Initiative: MONDO:0030913
OMIM®: 617751
Orphanet: ORPHA500159

Definition

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and moderate to severe intellectual disability, as well as variable other manifestations, such as macro- or microcephaly, epilepsy, hypotonia, behavioral problems, stereotypic movements, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, upturned nose, dysplastic ears, and broad mouth), among others. Brain imaging may show cerebellar anomalies, hypoplastic corpus callosum, enlarged ventricles, polymicrogyria, or white matter abnormalities. [from ORDO]

Clinical features

From HPO
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
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.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
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.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Cerebellar dysplasia
MedGen UID:
479952
Concept ID:
C3278322
Finding
Cerebellar dysplasia (abnormal growth or development) is defined by abnormal cerebellar foliation, white matter arborization, and gray-white matter junction. Cerebellar dysplasia is a neuroimaging finding that describes abnormalities of both the cerebellar cortex and white matter and is associated with variable neurodevelopmental outcome. Dysplasia may globally involve the cerebellum or affect only one cerebellar hemisphere. In addition, cerebellar dysplasia may be associated with cortical/subcortical cysts.
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.
Dysgenesis of the cerebellar vermis
MedGen UID:
871238
Concept ID:
C4025719
Anatomical Abnormality
Defective development of the vermis of cerebellum.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Enlarged cisterna magna
MedGen UID:
344031
Concept ID:
C1853377
Finding
Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.
Plagiocephaly
MedGen UID:
1825944
Concept ID:
C2081594
Finding
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Tracheobronchomalacia
MedGen UID:
137939
Concept ID:
C0340231
Disease or Syndrome
Williams-Campbell syndrome is a congenital disorder characterized by severe bronchiectasis and recurrent pulmonary infections caused by a cartilage abnormality involving the 4th-6th order subsegmental bronchi. It typically presents in infancy or childhood with symptoms of coughing, wheezing, and dyspnea. Imaging reveals normal central airways with severe bilateral cystic bronchiectasis in the subsegmental bronchi, often associated with bronchial wall thickening, mucous plugging, and bronchomalacia. During dynamic imaging, the abnormal bronchi will demonstrate ballooning on inspiratory imaging and collapse/air-trapping on expiratory imaging (summary by Marini et al., 2017).
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Long palpebral fissure
MedGen UID:
340300
Concept ID:
C1849340
Finding
Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Low hanging columella
MedGen UID:
344656
Concept ID:
C1856119
Finding
Columella extending inferior to the level of the nasal base, when viewed from the side.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Echogenic intracardiac focus
MedGen UID:
869212
Concept ID:
C4023634
Finding
A finding of a focus of increased echogenicity upon prenatal ultrasound examination of the fetus. The foci may be present in one or both ventricles. Echogenic intracardiac focus (EICF) is defined as a focus of echogenicity comparable to bone, in the region of the papillary muscle in either or both ventricles of the fetal heart.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIntellectual disability, autosomal dominant 48

Recent clinical studies

Etiology

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
Zhao J, Lyu G, Ding C, Wang X, Li J, Zhang W, Yang X, Zhang VW
Mol Genet Genomic Med 2022 Mar;10(3):e1825. Epub 2022 Feb 14 doi: 10.1002/mgg3.1825. PMID: 35156329Free PMC Article
Fagan AM, Henson RL, Li Y, Boerwinkle AH, Xiong C, Bateman RJ, Goate A, Ances BM, Doran E, Christian BT, Lai F, Rosas HD, Schupf N, Krinsky-McHale S, Silverman W, Lee JH, Klunk WE, Handen BL, Allegri RF, Chhatwal JP, Day GS, Graff-Radford NR, Jucker M, Levin J, Martins RN, Masters CL, Mori H, Mummery CJ, Niimi Y, Ringman JM, Salloway S, Schofield PR, Shoji M, Lott IT; Alzheimer's Biomarker Consortium–Down Syndrome; Dominantly Inherited Alzheimer Network
Lancet Neurol 2021 Aug;20(8):615-626. doi: 10.1016/S1474-4422(21)00139-3. PMID: 34302786Free PMC Article
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
Pekeles H, Accogli A, Boudrahem-Addour N, Russell L, Parente F, Srour M
Pediatr Neurol 2019 Mar;92:32-36. Epub 2018 Nov 22 doi: 10.1016/j.pediatrneurol.2018.11.005. PMID: 30581057

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
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
Fagan AM, Henson RL, Li Y, Boerwinkle AH, Xiong C, Bateman RJ, Goate A, Ances BM, Doran E, Christian BT, Lai F, Rosas HD, Schupf N, Krinsky-McHale S, Silverman W, Lee JH, Klunk WE, Handen BL, Allegri RF, Chhatwal JP, Day GS, Graff-Radford NR, Jucker M, Levin J, Martins RN, Masters CL, Mori H, Mummery CJ, Niimi Y, Ringman JM, Salloway S, Schofield PR, Shoji M, Lott IT; Alzheimer's Biomarker Consortium–Down Syndrome; Dominantly Inherited Alzheimer Network
Lancet Neurol 2021 Aug;20(8):615-626. doi: 10.1016/S1474-4422(21)00139-3. PMID: 34302786Free PMC Article
Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A
Lancet 2020 Jun 27;395(10242):1988-1997. doi: 10.1016/S0140-6736(20)30689-9. PMID: 32593336Free PMC Article
Pekeles H, Accogli A, Boudrahem-Addour N, Russell L, Parente F, Srour M
Pediatr Neurol 2019 Mar;92:32-36. Epub 2018 Nov 22 doi: 10.1016/j.pediatrneurol.2018.11.005. PMID: 30581057

Therapy

Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A
Lancet 2020 Jun 27;395(10242):1988-1997. doi: 10.1016/S0140-6736(20)30689-9. PMID: 32593336Free PMC Article

Prognosis

Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A
Lancet 2020 Jun 27;395(10242):1988-1997. doi: 10.1016/S0140-6736(20)30689-9. PMID: 32593336Free PMC Article
Franceschini P, Guala A, Vardeu MP, Signorile F, Franceschini D, Mastroiacovo P, Gianotti A, Livini E, Lalatta F, Selicorni A, Andria G, Scarano G, Della Monica M, Rizzo R, Zelante L, Stabile M, Gabrielli O, Neri G
Minerva Pediatr 1996 Oct;48(10):421-8. PMID: 9017917

Clinical prediction guides

Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A
Lancet 2020 Jun 27;395(10242):1988-1997. doi: 10.1016/S0140-6736(20)30689-9. PMID: 32593336Free PMC Article
Pottier C, Wallon D, Lecrux AR, Maltete D, Bombois S, Jurici S, Frebourg T, Hannequin D, Campion D
J Alzheimers Dis 2012;28(3):561-6. doi: 10.3233/JAD-2011-111148. PMID: 22045488
Querfurth HW, Wijsman EM, St George-Hyslop PH, Selkoe DJ
Brain Res Mol Brain Res 1995 Feb;28(2):319-37. doi: 10.1016/0169-328x(94)00224-3. PMID: 7723630

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...