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Corpus callosum, partial agenesis of, X-linked

MedGen UID:
374339
Concept ID:
C1839909
Disease or Syndrome
Synonyms: Corpus Callosum, Partial Agenesis of, X-Linked
Modes of inheritance:
X-linked inheritance
MedGen UID:
66838
Concept ID:
C0241764
Genetic Function
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on the X chromosome.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, 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.
X-linked recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): L1CAM (Xq28)
OMIM®: 304100
Orphanet: ORPHA1497

Definition

The phenotypic spectrum of L1 syndrome includes: • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS); • MASA syndrome (mental retardation, aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs); • SPG1 (X-linked complicated hereditary spastic paraplegia type 1); and • X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50). [from GTR]

Additional descriptions

From GeneReviews
The phenotypic spectrum of L1 syndrome includes: • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS); • MASA syndrome (mental retardation, aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs); • SPG1 (X-linked complicated hereditary spastic paraplegia type 1); and • X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50).  https://www.ncbi.nlm.nih.gov/books/NBK1484
From GHR
L1 syndrome describes a group of conditions that primarily affect the nervous system and occur almost exclusively in males. These conditions vary in severity and include, from most severe to least, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis.HSAS is an acronym for the characteristic features of the condition: a buildup of fluid in the brain (hydrocephalus) that is often present from before birth, muscle stiffness (spasticity), thumbs that are permanently bent toward the palms (adducted thumbs), and narrowing (stenosis) of a passageway in the brain called the aqueduct of Sylvius. In individuals with HSAS, stenosis of the aqueduct of Sylvius causes hydrocephalus by impeding the flow of cerebrospinal fluid (CSF) out of fluid-filled cavities called ventricles. Individuals with HSAS often have severe intellectual disability and may have seizures.MASA syndrome is also named for the characteristic features of the condition, which are intellectual disability (mental retardation) that can range from mild to moderate, delayed speech (aphasia), spasticity, and adducted thumbs. Individuals with MASA syndrome may have mild enlargement of the ventricles.Spastic paraplegia type 1 is characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the limbs (paraplegia). Affected individuals also have mild to moderate intellectual disability. People with spastic paraplegia type 1 do not usually have major abnormalities in structures of the brain.X-linked complicated corpus callosum agenesis is defined by underdevelopment (hypoplasia) or absence (agenesis) of the tissue that connects the left and right halves of the brain (the corpus callosum). People with this condition can have spastic paraplegia and mild to moderate intellectual disability.The life expectancy of individuals with L1 syndrome varies depending on the severity of the signs and symptoms. Severely affected individuals may survive only a short time after birth, while those with mild features live into adulthood.The conditions that make up L1 syndrome were once thought to be distinct disorders, but since they were found to share a genetic cause, they are now considered to be part of the same syndrome. Family members with L1 syndrome caused by the same mutation may have different forms of the condition.  https://ghr.nlm.nih.gov/condition/l1-syndrome

Clinical features

Aganglionic megacolon
MedGen UID:
6285
Concept ID:
C0025160
Pathologic Function
An abnormal dilation of the colon not due to obstruction.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
A brain disorder characterized by episodes of abnormally increased neuronal discharge resulting in transient episodes of sensory or motor neurological dysfunction, or psychic dysfunction. These episodes may or may not be associated with loss of consciousness or convulsions.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Aganglionic megacolon
MedGen UID:
6285
Concept ID:
C0025160
Pathologic Function
An abnormal dilation of the colon not due to obstruction.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Congenital cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Hypoplasia of the cerebellum that is associated with inherited metabolic disorders and neurodegenerative disorders. Signs and symptoms include mental and developmental delays, walking and balance difficulties, floppy muscle tone, and seizures.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Partial agenesis of corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
Inferior vermis hypoplasia
MedGen UID:
343328
Concept ID:
C1855350
Finding
Underdevelopment of the inferior portion of the vermis of cerebellum.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Abnormal facial shape
MedGen UID:
91281
Concept ID:
C0376634
Congenital Abnormality
An abnormal morphology (form) of the face or its components.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCorpus callosum, partial agenesis of, X-linked
Follow this link to review classifications for Corpus callosum, partial agenesis of, X-linked in Orphanet.

Recent clinical studies

Etiology

Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, Caligiuri G, Hobson L, Boyle J, Mansour A, Friend KL, Crawford J, Jackson G, Vandeleur L, Hackett A, Tarpey P, Stratton MR, Turner G, Gécz J, Field M
J Med Genet 2015 Apr;52(4):269-74. Epub 2015 Jan 22 doi: 10.1136/jmedgenet-2014-102418. PMID: 25612912

Diagnosis

Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, Caligiuri G, Hobson L, Boyle J, Mansour A, Friend KL, Crawford J, Jackson G, Vandeleur L, Hackett A, Tarpey P, Stratton MR, Turner G, Gécz J, Field M
J Med Genet 2015 Apr;52(4):269-74. Epub 2015 Jan 22 doi: 10.1136/jmedgenet-2014-102418. PMID: 25612912
Mayr JA, Koch J, Fauth C, Zimmermann FA, Rauscher C, Zschocke J, Sperl W
Neuropediatrics 2012 Jun;43(3):130-4. Epub 2012 Apr 2 doi: 10.1055/s-0032-1309308. PMID: 22473288
Gripp KW, Hopkins E, Johnston JJ, Krause C, Dobyns WB, Biesecker LG
Am J Med Genet A 2011 Oct;155A(10):2516-20. Epub 2011 Sep 9 doi: 10.1002/ajmg.a.34190. PMID: 21910224Free PMC Article
Lerma-Carrillo I, Molina JD, Cuevas-Duran T, Julve-Correcher C, Espejo-Saavedra JM, Andrade-Rosa C, Lopez-Muñoz F
Am J Med Genet A 2006 Dec 15;140(24):2807-11. doi: 10.1002/ajmg.a.31503. PMID: 17036352
Timor-Tritsch IE, Monteagudo A, Haratz-Rubinstein N, Levine RU
Prenat Diagn 1996 Jun;16(6):543-8. doi: 10.1002/(SICI)1097-0223(199606)16:6<543::AID-PD878>3.0.CO;2-I. PMID: 8809896

Prognosis

Gripp KW, Hopkins E, Johnston JJ, Krause C, Dobyns WB, Biesecker LG
Am J Med Genet A 2011 Oct;155A(10):2516-20. Epub 2011 Sep 9 doi: 10.1002/ajmg.a.34190. PMID: 21910224Free PMC Article
Donnenfeld AE, Packer RJ, Zackai EH, Chee CM, Sellinger B, Emanuel BS
Am J Med Genet 1989 Apr;32(4):461-7. doi: 10.1002/ajmg.1320320405. PMID: 2773986

Clinical prediction guides

Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, Caligiuri G, Hobson L, Boyle J, Mansour A, Friend KL, Crawford J, Jackson G, Vandeleur L, Hackett A, Tarpey P, Stratton MR, Turner G, Gécz J, Field M
J Med Genet 2015 Apr;52(4):269-74. Epub 2015 Jan 22 doi: 10.1136/jmedgenet-2014-102418. PMID: 25612912
Giampietro PF, Babu D, Koehn MA, Jacobson DM, Mueller-Schrader KA, Moretti C, Patten SF, Shaffer LG, Gorlin RJ, Dobyns WB
Am J Med Genet A 2004 Jan 15;124A(2):202-8. doi: 10.1002/ajmg.a.20377. PMID: 14699622
Boyd E, Schwartz CE, Schroer RJ, May MM, Shapiro SD, Arena JF, Lubs HA, Stevenson RE
Clin Dysmorphol 1993 Oct;2(4):332-41. PMID: 8305964
Donnenfeld AE, Graham JM Jr, Packer RJ, Aquino R, Berg SZ, Emanuel BS
Am J Med Genet 1990 Oct;37(2):182-6. doi: 10.1002/ajmg.1320370205. PMID: 2248284

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