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Intellectual disability, X-linked syndromic, Turner type(MRXST)

MedGen UID:
394425
Concept ID:
C2678046
Disease or Syndrome
Synonyms: Brooks Wisniewski Brown syndrome; INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, TURNER TYPE; MENTAL RETARDATION AND MACROCEPHALY SYNDROME; MENTAL RETARDATION, X-LINKED, SYNDROMIC, BROOKS-WISNIEWSKI-BROWN TYPE; Mental retardation, X-linked, syndromic, Turner type; MENTAL RETARDATION, X-LINKED, WITH GROWTH RETARDATION, DEAFNESS, AND MICROGENITALISM; MRXST; X-linked intellectual disability, Turner type; X-linked mental retardation Brooks type
SNOMED CT: X-linked intellectual disability Brooks type (725912001); Brooks Wisniewski Brown syndrome (725912001)
 
Gene (location): HUWE1 (Xp11.22)
 
Monarch Initiative: MONDO:0010407
OMIM®: 309590
Orphanet: ORPHA85328

Definition

Turner-type X-linked syndromic intellectual developmental disorder (MRXST) is a neurodevelopmental disorder with a highly variable phenotype. Some affected families show X-linked recessive inheritance, with only males being affected and carrier females having no abnormal findings. In other affected families, males are severely affected, and female mutation carriers show milder cognitive abnormalities or dysmorphic features. In addition, there are female patients with de novo mutations who show the full phenotype, despite skewed X-chromosome inactivation. Affected individuals show global developmental delay from infancy, with variably impaired intellectual development and poor or absent speech, often with delayed walking. Dysmorphic features are common and can include macrocephaly, microcephaly, deep-set eyes, hypotelorism, small palpebral fissures, dysplastic, large, or low-set ears, long face, bitemporal narrowing, high-arched palate, thin upper lip, and scoliosis or mild distal skeletal anomalies, such as brachydactyly or tapered fingers. Males tend to have cryptorchidism. Other features, such as hypotonia, seizures, and delayed bone age, are more variable (summary by Moortgat et al., 2018). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
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.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
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.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Cupped ear
MedGen UID:
335186
Concept ID:
C1845447
Congenital Abnormality
Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Spastic diplegia
MedGen UID:
44181
Concept ID:
C0023882
Disease or Syndrome
Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.
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
Finding
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
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.
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.
Poor coordination
MedGen UID:
107874
Concept ID:
C0563243
Finding
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
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.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
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.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Short palpebral fissure
MedGen UID:
98067
Concept ID:
C0423112
Finding
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Epicanthus inversus
MedGen UID:
224913
Concept ID:
C1303003
Finding
A fold of skin starting at or just below the medial aspect of the lower lid and arching upward to cover, extend in front of and lateral to the medial canthus.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Low posterior hairline
MedGen UID:
383755
Concept ID:
C1855728
Finding
Hair on the neck extends more inferiorly than usual.
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.
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).
Oligodontia
MedGen UID:
904670
Concept ID:
C4082304
Congenital Abnormality
The absence of six or more teeth from the normal series by a failure to develop.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
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).
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
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.
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

Diagnosis

Semyachkina AN, Voskoboeva EY, Zakharova EY, Nikolaeva EA, Kanivets IV, Kolotii AD, Baydakova GV, Kharabadze MN, Kuramagomedova RG, Melnikova NV
BMC Med Genet 2019 May 2;20(1):66. doi: 10.1186/s12881-019-0807-x. PMID: 31046699Free PMC Article
Altarescu G, Reish O, Renbaum P, Kasterstein E, Komarovsky D, Komsky A, Bern O, Strassburger D, Levy-Lahad E, Ron-El R
J Assist Reprod Genet 2011 Mar;28(3):233-8. Epub 2010 Dec 1 doi: 10.1007/s10815-010-9508-2. PMID: 21120598Free PMC Article

Therapy

Semyachkina AN, Voskoboeva EY, Zakharova EY, Nikolaeva EA, Kanivets IV, Kolotii AD, Baydakova GV, Kharabadze MN, Kuramagomedova RG, Melnikova NV
BMC Med Genet 2019 May 2;20(1):66. doi: 10.1186/s12881-019-0807-x. PMID: 31046699Free PMC Article

Clinical prediction guides

Malmgren H, Sundvall M, Dahl N, Gustavson KH, Annerén G, Wadelius C, Steén-Bondeson ML, Pettersson U
Am J Hum Genet 1993 Jun;52(6):1046-52. PMID: 8503440Free PMC Article