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Intellectual developmental disorder, X-linked 108(MRX108)

MedGen UID:
1680544
Concept ID:
C5193009
Disease or Syndrome
Synonym: MENTAL RETARDATION, X-LINKED 108
 
Gene (location): SLC9A7 (Xp11.3)
 
Monarch Initiative: MONDO:0026723
OMIM®: 301024

Definition

X-linked intellectual developmental disorder-108 (MRX108) is characterized by early hypotonia, global developmental delay, and moderately to severely impaired intellectual development. Brisk tendon reflexes, variable facial dysmorphism, and fifth finger clinodactyly may be present (Khayat et al., 2019). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Overweight
MedGen UID:
105424
Concept ID:
C0497406
Finding
Increased body weight with a body mass index of 25-29.9 kg per square meter.
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.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
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.
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 disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
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.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months 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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Myopathic facies
MedGen UID:
90695
Concept ID:
C0332615
Finding
A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
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.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip 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).
High anterior hairline
MedGen UID:
477667
Concept ID:
C3276036
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
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

Goldstein DS, Holmes CS, Kaler SG
Neurochem Res 2009 Aug;34(8):1464-8. Epub 2009 Feb 21 doi: 10.1007/s11064-009-9933-8. PMID: 19234788Free PMC Article

Recent clinical studies

Etiology

Kühl JS, Kupper J, Baqué H, Ebell W, Gärtner J, Korenke C, Spors B, Steffen IG, Strauss G, Voigt S, Weschke B, Weddige A, Köhler W, Steinfeld R
JAMA Netw Open 2018 Jul 6;1(3):e180769. doi: 10.1001/jamanetworkopen.2018.0769. PMID: 30646031Free PMC Article
Goldstein DS, Holmes CS, Kaler SG
Neurochem Res 2009 Aug;34(8):1464-8. Epub 2009 Feb 21 doi: 10.1007/s11064-009-9933-8. PMID: 19234788Free PMC Article
Vachalova I, Chandoga J, Petrovic R, Copikova-Cudrakova D, Sykora M, Traubner P
Bratisl Lek Listy 2007;108(10-11):462-6. PMID: 18306728
Stephenson JB, Hoffman MC, Russell AJ, Falconer J, Beach RC, Tolmie JL, McWilliam RC, Zuberi SM
Brain Dev 2005 Mar;27(2):108-13. doi: 10.1016/j.braindev.2003.11.010. PMID: 15668049
Kohn M, Kehrer-Sawatzki H, Hameister H
Cytogenet Genome Res 2005;108(4):342-7. doi: 10.1159/000081529. PMID: 15627755

Diagnosis

Schwartz CE, Louie RJ, Toutain A, Skinner C, Friez MJ, Stevenson RE
Am J Med Genet A 2023 Jan;191(1):144-159. Epub 2022 Oct 27 doi: 10.1002/ajmg.a.63008. PMID: 36300573
Hashem SI, Murphy AN, Divakaruni AS, Klos ML, Nelson BC, Gault EC, Rowland TJ, Perry CN, Gu Y, Dalton ND, Bradford WH, Devaney EJ, Peterson KL, Jones KL, Taylor MRG, Chen J, Chi NC, Adler ED
J Mol Cell Cardiol 2017 Jul;108:86-94. Epub 2017 May 16 doi: 10.1016/j.yjmcc.2017.05.007. PMID: 28526246
Fu F, Liu HL, Li R, Han J, Yang X, Min P, Zhen L, Zhang YL, Xie GE, Lei TY, Li Y, Li J, Li DZ, Liao C
Gene 2014 Aug 10;546(2):222-5. Epub 2014 Jun 7 doi: 10.1016/j.gene.2014.06.012. PMID: 24914495
Vachalova I, Chandoga J, Petrovic R, Copikova-Cudrakova D, Sykora M, Traubner P
Bratisl Lek Listy 2007;108(10-11):462-6. PMID: 18306728
Neville L, Cochrane J, Fitzgerald P, Kennedy M
N Z Med J 1995 Oct 13;108(1009):404-6. PMID: 7478333

Therapy

Tanaka H, Amano N, Tanaka K, Katsuki T, Adachi T, Shimozawa N, Kawai T
Endocr J 2020 Jun 29;67(6):655-658. Epub 2020 Feb 26 doi: 10.1507/endocrj.EJ19-0576. PMID: 32101828
Fu F, Liu HL, Li R, Han J, Yang X, Min P, Zhen L, Zhang YL, Xie GE, Lei TY, Li Y, Li J, Li DZ, Liao C
Gene 2014 Aug 10;546(2):222-5. Epub 2014 Jun 7 doi: 10.1016/j.gene.2014.06.012. PMID: 24914495
Kaplan PW, Tusa RJ, Shankroff J, Heller J, Moser HW
Ann Neurol 1993 Aug;34(2):169-74. doi: 10.1002/ana.410340212. PMID: 8338341

Prognosis

Tanaka H, Amano N, Tanaka K, Katsuki T, Adachi T, Shimozawa N, Kawai T
Endocr J 2020 Jun 29;67(6):655-658. Epub 2020 Feb 26 doi: 10.1507/endocrj.EJ19-0576. PMID: 32101828
Iida A, Takano K, Takeshita E, Abe-Hatano C, Hirabayashi S, Inaba Y, Kosugi S, Kamatani Y, Momozawa Y, Kubo M, Nakagawa E, Inoue K, Goto YI
Cold Spring Harb Mol Case Stud 2019 Dec;5(6) Epub 2019 Dec 13 doi: 10.1101/mcs.a003988. PMID: 31444167Free PMC Article

Clinical prediction guides

Iida A, Takano K, Takeshita E, Abe-Hatano C, Hirabayashi S, Inaba Y, Kosugi S, Kamatani Y, Momozawa Y, Kubo M, Nakagawa E, Inoue K, Goto YI
Cold Spring Harb Mol Case Stud 2019 Dec;5(6) Epub 2019 Dec 13 doi: 10.1101/mcs.a003988. PMID: 31444167Free PMC Article
Kühl JS, Kupper J, Baqué H, Ebell W, Gärtner J, Korenke C, Spors B, Steffen IG, Strauss G, Voigt S, Weschke B, Weddige A, Köhler W, Steinfeld R
JAMA Netw Open 2018 Jul 6;1(3):e180769. doi: 10.1001/jamanetworkopen.2018.0769. PMID: 30646031Free PMC Article
Harper CB, Mancini GMS, van Slegtenhorst M, Cousin MA
Neurobiol Dis 2017 Dec;108:298-306. Epub 2017 Sep 5 doi: 10.1016/j.nbd.2017.08.021. PMID: 28887151Free PMC Article
Ramos HE
Endocr Dev 2014;26:108-17. Epub 2014 Aug 29 doi: 10.1159/000363158. PMID: 25231447

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