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Syndromic X-linked intellectual disability Snyder type(MRXSSR)

MedGen UID:
162918
Concept ID:
C0796160
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE; MRXSSR; Snyder Robinson syndrome; SNYDER-ROBINSON MENTAL RETARDATION SYNDROME; Spermine synthase deficiency; X-linked mental retardation Snyder - Robinson type
SNOMED CT: Snyder-Robinson syndrome (702416008); Snyder-Robinson x-linked mental retardation syndrome (702416008); Mental retardation, x-linked, Snyder-Robinson type (702416008); X-linked intellectual disability Snyder type (702416008)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): SMS (Xp22.11)
 
Monarch Initiative: MONDO:0010664
OMIM®: 309583
Orphanet: ORPHA3063

Disease characteristics

Excerpted from the GeneReview: Snyder-Robinson Syndrome
Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome characterized by asthenic build, facial dysmorphism with a prominent lower lip, kyphoscoliosis, osteoporosis, speech abnormalities, and seizures. Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound intellectual disability (which appears to remain stable over time) and variable motor disability. Asthenic habitus and low muscle mass usually develop during the first year, even in males who are ambulatory. During the first decade, males with SRS develop osteoporosis, resulting in fractures in the absence of trauma. [from GeneReviews]
Authors:
Charles E Schwartz  |  Angela Peron  |  Mary Jo Kutler   view full author information

Additional descriptions

From OMIM
Snyder-Robinson X-linked syndromic intellectual developmental disorder (MRXSSR) is an X-linked intellectual disability syndrome with characteristic features including facial asymmetry, marfanoid habitus, unsteady gait, thickened lower lip, nasal dysarthric speech, narrow or cleft palate, diminished muscle mass, osteoporosis, kyphoscoliosis, long great toes, short stature, pectus carinatum, and myopia (summary by Zhang et al., 2013).  http://www.omim.org/entry/309583
From MedlinePlus Genetics
Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.

Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.

Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.

Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.

Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys.  https://medlineplus.gov/genetics/condition/snyder-robinson-syndrome

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).
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Narrow palm
MedGen UID:
346628
Concept ID:
C1857632
Finding
For children from birth to 4 years of age, the palm width is more than 2 SD below the mean; for children from 4 to 16 years of age the palm width is below the 5th centile; or, the width of the palm appears disproportionately narrow for its length.
Long fingers
MedGen UID:
346836
Concept ID:
C1858091
Finding
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
Long hallux
MedGen UID:
400514
Concept ID:
C1864375
Finding
Increased length of the big toe.
Long palm
MedGen UID:
869005
Concept ID:
C4023422
Finding
For children from birth to 16 years of age the length of the palm is more than the 97th centile; or, the length of the palm appears relatively long compared to the finger length or the limb length.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
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).
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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.
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.
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.
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.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
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.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
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.
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Thin bony cortex
MedGen UID:
318844
Concept ID:
C1833325
Finding
Abnormal thinning of the cortical region of bones.
Decreased muscle mass
MedGen UID:
373256
Concept ID:
C1837108
Finding
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
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.
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Hypernasal speech
MedGen UID:
107884
Concept ID:
C0566620
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Webbed neck
MedGen UID:
113154
Concept ID:
C0221217
Congenital Abnormality
Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
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.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
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).
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).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
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.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Wide intermamillary distance
MedGen UID:
473489
Concept ID:
C1827524
Finding
A larger than usual distance between the left and right nipple.
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).
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).
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSyndromic X-linked intellectual disability Snyder type
Follow this link to review classifications for Syndromic X-linked intellectual disability Snyder type in Orphanet.

Recent clinical studies

Diagnosis

Zhang Z, Norris J, Schwartz C, Alexov E
PLoS One 2011;6(5):e20373. Epub 2011 May 27 doi: 10.1371/journal.pone.0020373. PMID: 21647366Free PMC Article

Prognosis

Larcher L, Norris JW, Lejeune E, Buratti J, Mignot C, Garel C, Keren B, Schwartz CE, Whalen S
Eur J Med Genet 2020 Apr;63(4):103777. Epub 2019 Sep 30 doi: 10.1016/j.ejmg.2019.103777. PMID: 31580924
Peng Y, Norris J, Schwartz C, Alexov E
Int J Mol Sci 2016 Jan 8;17(1) doi: 10.3390/ijms17010077. PMID: 26761001Free PMC Article
Zhang Z, Norris J, Schwartz C, Alexov E
PLoS One 2011;6(5):e20373. Epub 2011 May 27 doi: 10.1371/journal.pone.0020373. PMID: 21647366Free PMC Article
Zhang Z, Teng S, Wang L, Schwartz CE, Alexov E
Hum Mutat 2010 Sep;31(9):1043-9. doi: 10.1002/humu.21310. PMID: 20556796Free PMC Article

Clinical prediction guides

Peng Y, Norris J, Schwartz C, Alexov E
Int J Mol Sci 2016 Jan 8;17(1) doi: 10.3390/ijms17010077. PMID: 26761001Free PMC Article
Zhang Z, Norris J, Schwartz C, Alexov E
PLoS One 2011;6(5):e20373. Epub 2011 May 27 doi: 10.1371/journal.pone.0020373. PMID: 21647366Free PMC Article
Zhang Z, Teng S, Wang L, Schwartz CE, Alexov E
Hum Mutat 2010 Sep;31(9):1043-9. doi: 10.1002/humu.21310. PMID: 20556796Free PMC Article

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