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MECP2 duplication syndrome(MRXSL)

MedGen UID:
337496
Concept ID:
C1846058
Disease or Syndrome
Synonyms: Lubs X-linked mental retardation syndrome; Mental retardation, X-linked, Lubs type; MENTAL RETARDATION, X-LINKED, SYNDROMIC, LUBS TYPE; MENTAL RETARDATION, X-LINKED, WITH RECURRENT RESPIRATORY INFECTIONS; MRXSL; XLMR syndrome, Lubs type
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
425042
Concept ID:
CN001297
Genetic Function
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: MECP2
Cytogenetic location: Xq28
OMIM®: 300260
Orphanet: ORPHA1762

Disease characteristics

Excerpted from the GeneReview: MECP2 Duplication Syndrome
The MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by infantile hypotonia, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals) and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and related clinical findings, often associated with concomitant X-chromosomal abnormalities that prevent inactivation of the duplicated region. Generalized tonic-clonic seizures are most often observed; atonic seizures and absence seizures have also been described. One third of affected males are never able to walk independently. Almost 50% of affected males die before age 25 years, presumably from complications of recurrent infection and/or neurologic deterioration. In addition to the core features, autistic behaviors and gastrointestinal dysfunction have been observed in several affected boys. Although interfamilial phenotypic variability is observed, severity is usually consistent within families.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Hilde Van Esch   view full author information

Additional descriptions

From OMIM
MECP2 duplication syndrome is an X-linked neurodevelopmental disorder characterized by severe to profound mental retardation, infantile hypotonia, mild dysmorphic features, poor speech development, autistic features, seizures, progressive spasticity, and recurrent infections. Only males are affected, although female carriers may have some mild neuropsychiatric features, such as anxiety. Submicroscopic Xq28 duplications encompassing MECP2 are considered nonrecurrent events, because the breakpoint locations and rearrangement sizes vary among affected individuals (summary by Ramocki et al., 2010).  http://www.omim.org/entry/300260
From GHR
MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, seizures that may not improve with treatment, or muscle stiffness (spasticity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately one third of people with this condition cannot walk without assistance. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with almost half succumbing by age 25.  http://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome

Clinical features

Cryptorchidism
MedGen UID:
504309
Concept ID:
CN000029
Finding
Absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Narrow mouth
MedGen UID:
504373
Concept ID:
CN000156
Finding
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Abnormality of the teeth
MedGen UID:
424982
Concept ID:
CN000160
Finding
Any abnormality of the teeth.
Brachycephaly
MedGen UID:
504407
Concept ID:
CN000240
Finding
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.
Drooling
MedGen UID:
505191
Concept ID:
CN002095
Finding
Habitual flow of saliva out of the mouth.
Depressed nasal bridge
MedGen UID:
446656
Concept ID:
CN004681
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Low-set ears
MedGen UID:
504425
Concept ID:
CN000345
Finding
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.
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Rigidity
MedGen UID:
505075
Concept ID:
CN001866
Finding
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Chorea
MedGen UID:
505081
Concept ID:
CN001874
Finding
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion.
Drooling
MedGen UID:
505191
Concept ID:
CN002095
Finding
Habitual flow of saliva out of the mouth.
Bruxism
MedGen UID:
505591
Concept ID:
CN003399
Finding
Bruxism is characterized by the grinding of the teeth including the clenching of the jaw and typically occur during sleep.
Severe global developmental delay
MedGen UID:
506566
Concept ID:
CN167072
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Brachycephaly
MedGen UID:
504407
Concept ID:
CN000240
Finding
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.
Gastroesophageal reflux
MedGen UID:
505057
Concept ID:
CN001828
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Growth delay
MedGen UID:
500905
Concept ID:
CN001379
Finding
A deficiency or slowing down of growth pre- and postnatally.
Infantile muscular hypotonia
MedGen UID:
426035
Concept ID:
CN007871
Finding
Muscular hypotonia (abnormally low muscle tone) manifesting in infancy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGMECP2 duplication syndrome

Recent clinical studies

Etiology

Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB
Autism Res 2013 Feb;6(1):42-50. Epub 2012 Nov 20 doi: 10.1002/aur.1262. [Epub ahead of print] PMID: 23169761Free PMC Article
Ben-Shachar S, Chahrour M, Thaller C, Shaw CA, Zoghbi HY
Hum Mol Genet 2009 Jul 1;18(13):2431-42. Epub 2009 Apr 15 doi: 10.1093/hmg/ddp181. [Epub ahead of print] PMID: 19369296Free PMC Article

Diagnosis

Peters SU, Hundley RJ, Wilson AK, Carvalho CM, Lupski JR, Ramocki MB
J Autism Dev Disord 2013 Oct;43(10):2484-90. doi: 10.1007/s10803-013-1796-9. PMID: 23456562
Shimada S, Okamoto N, Ito M, Arai Y, Momosaki K, Togawa M, Maegaki Y, Sugawara M, Shimojima K, Osawa M, Yamamoto T
Brain Dev 2013 May;35(5):411-9. Epub 2012 Aug 9 doi: 10.1016/j.braindev.2012.07.010. [Epub ahead of print] PMID: 22877836
Vignoli A, Borgatti R, Peron A, Zucca C, Ballarati L, Bonaglia C, Bellini M, Giordano L, Romaniello R, Bedeschi MF, Epifanio R, Russo S, Caselli R, Giardino D, Darra F, La Briola F, Banderali G, Canevini MP
Epilepsia 2012 Jul;53(7):1146-55. Epub 2012 May 11 doi: 10.1111/j.1528-1167.2012.03501.x. [Epub ahead of print] PMID: 22578097
Ramocki MB, Tavyev YJ, Peters SU
Am J Med Genet A 2010 May;152A(5):1079-88. doi: 10.1002/ajmg.a.33184. PMID: 20425814Free PMC Article
Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP, Richman R, Fang P, Glaze DG, Lupski JR, Zoghbi HY
Ann Neurol 2009 Dec;66(6):771-82. doi: 10.1002/ana.21715. PMID: 20035514Free PMC Article

Therapy

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. [Epub ahead of print] PMID: 24914495
Shimada S, Okamoto N, Ito M, Arai Y, Momosaki K, Togawa M, Maegaki Y, Sugawara M, Shimojima K, Osawa M, Yamamoto T
Brain Dev 2013 May;35(5):411-9. Epub 2012 Aug 9 doi: 10.1016/j.braindev.2012.07.010. [Epub ahead of print] PMID: 22877836
Mayo S, Monfort S, Roselló M, Orellana C, Oltra S, Armstrong J, Català V, Martínez F
Cytogenet Genome Res 2011;135(2):93-101. Epub 2011 Sep 16 doi: 10.1159/000330917. [Epub ahead of print] PMID: 21934280

Prognosis

Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB
Autism Res 2013 Feb;6(1):42-50. Epub 2012 Nov 20 doi: 10.1002/aur.1262. [Epub ahead of print] PMID: 23169761Free PMC Article
Honda S, Hayashi S, Nakane T, Imoto I, Kurosawa K, Mizuno S, Okamoto N, Kato M, Yoshihashi H, Kubota T, Nakagawa E, Goto Y, Inazawa J
Am J Med Genet A 2012 Jun;158A(6):1292-303. Epub 2012 Apr 23 doi: 10.1002/ajmg.a.35321. [Epub ahead of print] PMID: 22528406
Tang SS, Fernandez D, Lazarou LP, Singh R, Fallon P
Eur J Paediatr Neurol 2012 Mar;16(2):209-12. Epub 2011 Aug 6 doi: 10.1016/j.ejpn.2011.07.011. [Epub ahead of print] PMID: 21821449
McWilliam C, Cooke A, Lobo D, Warner J, Taylor M, Tolmie JL
Eur J Paediatr Neurol 2010 May;14(3):267-9. Epub 2009 Jul 9 doi: 10.1016/j.ejpn.2009.06.007. [Epub ahead of print] PMID: 19592282

Clinical prediction guides

Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB
Autism Res 2013 Feb;6(1):42-50. Epub 2012 Nov 20 doi: 10.1002/aur.1262. [Epub ahead of print] PMID: 23169761Free PMC Article
Vignoli A, Borgatti R, Peron A, Zucca C, Ballarati L, Bonaglia C, Bellini M, Giordano L, Romaniello R, Bedeschi MF, Epifanio R, Russo S, Caselli R, Giardino D, Darra F, La Briola F, Banderali G, Canevini MP
Epilepsia 2012 Jul;53(7):1146-55. Epub 2012 May 11 doi: 10.1111/j.1528-1167.2012.03501.x. [Epub ahead of print] PMID: 22578097
Honda S, Hayashi S, Nakane T, Imoto I, Kurosawa K, Mizuno S, Okamoto N, Kato M, Yoshihashi H, Kubota T, Nakagawa E, Goto Y, Inazawa J
Am J Med Genet A 2012 Jun;158A(6):1292-303. Epub 2012 Apr 23 doi: 10.1002/ajmg.a.35321. [Epub ahead of print] PMID: 22528406
Honda S, Satomura S, Hayashi S, Imoto I, Nakagawa E, Goto Y, Inazawa J; Japanese Mental Retardation Consortium
J Hum Genet 2012 Jan;57(1):73-7. Epub 2011 Dec 1 doi: 10.1038/jhg.2011.131. [Epub ahead of print] PMID: 22129561
Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP, Richman R, Fang P, Glaze DG, Lupski JR, Zoghbi HY
Ann Neurol 2009 Dec;66(6):771-82. doi: 10.1002/ana.21715. PMID: 20035514Free PMC Article

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