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L1 syndrome

MedGen UID:
1830362
Concept ID:
C5779710
Disease or Syndrome
Synonyms: Corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome; corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome; CRASH syndrome; Hypoplasia of corpus callosum and mental retardation with adducted thumbs and spasticity and hydrocephalus syndrome; Hypoplasia of corpus callosum, intellectual disability, adducted thumbs, spasticity, hydrocephalus syndrome; L1CAM syndrome
SNOMED CT: Hypoplasia of corpus callosum and mental retardation with adducted thumbs and spasticity and hydrocephalus syndrome (716996008); L1 syndrome (716996008); CRASH syndrome (716996008); Hypoplasia of corpus callosum, intellectual disability, adducted thumbs, spasticity, hydrocephalus syndrome (716996008)
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.
 
Related gene: L1CAM
 
Monarch Initiative: MONDO:0017140
Orphanet: ORPHA275543

Disease characteristics

Excerpted from the GeneReview: L1 Syndrome
L1 syndrome involves a phenotypic spectrum ranging from severe to mild and includes three clinical phenotypes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS). MASA (mental retardation [intellectual disability], aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs) syndrome including X-linked complicated hereditary spastic paraplegia type 1. 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). It is important to note that all phenotypes can be observed in affected individuals within the same family. [from GeneReviews]
Authors:
Connie Stumpel  |  Yvonne J Vos   view full author information

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/l1-syndrome

Professional guidelines

PubMed

Adle-Biassette H, Saugier-Veber P, Fallet-Bianco C, Delezoide AL, Razavi F, Drouot N, Bazin A, Beaufrère AM, Bessières B, Blesson S, Bucourt M, Carles D, Devisme L, Dijoud F, Fabre B, Fernandez C, Gaillard D, Gonzales M, Jossic F, Joubert M, Laurent N, Leroy B, Loeuillet L, Loget P, Marcorelles P, Martinovic J, Perez MJ, Satge D, Sinico M, Tosi M, Benichou J, Gressens P, Frebourg T, Laquerrière A
Acta Neuropathol 2013 Sep;126(3):427-42. Epub 2013 Jul 3 doi: 10.1007/s00401-013-1146-1. PMID: 23820807
Yamasaki M, Nonaka M, Suzumori N, Nakamura H, Fujita H, Namba A, Kamei Y, Yamada T, Pooh RK, Tanemura M, Sudo N, Nagasaka M, Yoshioka E, Shofuda T, Kanemura Y
J Neurosurg Pediatr 2011 Oct;8(4):411-6. doi: 10.3171/2011.7.PEDS10531. PMID: 21961551
Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, Fortuna AM, Sunde LE, Stolte-Dijkstra I, Schrander-Stumpel CT, Hofstra RM
J Med Genet 2010 Mar;47(3):169-75. Epub 2009 Oct 20 doi: 10.1136/jmg.2009.071688. PMID: 19846429

Recent clinical studies

Etiology

Varagur K, Sanka SA, Strahle JM
Neurosurg Clin N Am 2022 Jan;33(1):67-79. doi: 10.1016/j.nec.2021.09.006. PMID: 34801143Free PMC Article
Accogli A, Goergen S, Izzo G, Mankad K, Krajden Haratz K, Parazzini C, Fahey M, Menzies L, Baptista J, Carpineta L, Tortora D, Fulcheri E, Gaetano Vellone V, Paladini D, Spaccini L, Toto V, Trayers C, Ben Sira L, Reches A, Malinger G, Salpietro V, De Marco P, Srour M, Zara F, Capra V, Rossi A, Severino M
Ann Clin Transl Neurol 2021 Oct;8(10):2004-2012. Epub 2021 Sep 12 doi: 10.1002/acn3.51448. PMID: 34510796Free PMC Article
Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT
J Clin Endocrinol Metab 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631. PMID: 31504653Free PMC Article
Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, Fortuna AM, Sunde LE, Stolte-Dijkstra I, Schrander-Stumpel CT, Hofstra RM
J Med Genet 2010 Mar;47(3):169-75. Epub 2009 Oct 20 doi: 10.1136/jmg.2009.071688. PMID: 19846429
Nagaraj K, Kristiansen LV, Skrzynski A, Castiella C, Garcia-Alonso L, Hortsch M
Hum Mol Genet 2009 Oct 15;18(20):3822-31. Epub 2009 Jul 19 doi: 10.1093/hmg/ddp325. PMID: 19617634Free PMC Article

Diagnosis

Yao Y, Qiu L, Wei X, Chen J, Choy KW, Zheng G, Yang T, Li S, Yang F
Cell Biochem Funct 2024 Jun;42(4):e4034. doi: 10.1002/cbf.4034. PMID: 38715189
He T, Yao Q, Xu B, Yang M, Jiang J, Xiang Q, Xiao L, Liu S, Wang H, Zhang X
Mol Genet Genomic Med 2023 Nov;11(11):e2253. Epub 2023 Jul 24 doi: 10.1002/mgg3.2253. PMID: 37489051Free PMC Article
Wang P, Liao H, Wang Q, Xie H, Wang H, Yang M, Liu S
Reprod Sci 2022 Mar;29(3):768-780. Epub 2021 Dec 16 doi: 10.1007/s43032-021-00828-4. PMID: 34914080Free PMC Article
Christaller WA, Vos Y, Gebre-Medhin S, Hofstra RM, Schäfer MK
Clin Genet 2017 Jan;91(1):115-120. Epub 2016 Mar 15 doi: 10.1111/cge.12763. PMID: 26891472
Engle EC
Cold Spring Harb Perspect Biol 2010 Mar;2(3):a001784. doi: 10.1101/cshperspect.a001784. PMID: 20300212Free PMC Article

Therapy

Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H, Yamasaki M
J Neurosurg 2006 Nov;105(5 Suppl):403-12. doi: 10.3171/ped.2006.105.5.403. PMID: 17328266

Prognosis

Christaller WA, Vos Y, Gebre-Medhin S, Hofstra RM, Schäfer MK
Clin Genet 2017 Jan;91(1):115-120. Epub 2016 Mar 15 doi: 10.1111/cge.12763. PMID: 26891472
Adle-Biassette H, Saugier-Veber P, Fallet-Bianco C, Delezoide AL, Razavi F, Drouot N, Bazin A, Beaufrère AM, Bessières B, Blesson S, Bucourt M, Carles D, Devisme L, Dijoud F, Fabre B, Fernandez C, Gaillard D, Gonzales M, Jossic F, Joubert M, Laurent N, Leroy B, Loeuillet L, Loget P, Marcorelles P, Martinovic J, Perez MJ, Satge D, Sinico M, Tosi M, Benichou J, Gressens P, Frebourg T, Laquerrière A
Acta Neuropathol 2013 Sep;126(3):427-42. Epub 2013 Jul 3 doi: 10.1007/s00401-013-1146-1. PMID: 23820807
Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, Fortuna AM, Sunde LE, Stolte-Dijkstra I, Schrander-Stumpel CT, Hofstra RM
J Med Genet 2010 Mar;47(3):169-75. Epub 2009 Oct 20 doi: 10.1136/jmg.2009.071688. PMID: 19846429
Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H, Yamasaki M
J Neurosurg 2006 Nov;105(5 Suppl):403-12. doi: 10.3171/ped.2006.105.5.403. PMID: 17328266

Clinical prediction guides

Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT
J Clin Endocrinol Metab 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631. PMID: 31504653Free PMC Article
Isik E, Onay H, Atik T, Akgun B, Cogulu O, Ozkinay F
Clin Neurol Neurosurg 2018 Sep;172:20-23. Epub 2018 Jun 18 doi: 10.1016/j.clineuro.2018.06.007. PMID: 29960101
Christaller WA, Vos Y, Gebre-Medhin S, Hofstra RM, Schäfer MK
Clin Genet 2017 Jan;91(1):115-120. Epub 2016 Mar 15 doi: 10.1111/cge.12763. PMID: 26891472
Tagliavacca L, Colombo F, Racchetti G, Meldolesi J
J Neurochem 2013 Feb;124(3):397-409. Epub 2012 Dec 10 doi: 10.1111/jnc.12015. PMID: 22973895Free PMC Article
Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, Fortuna AM, Sunde LE, Stolte-Dijkstra I, Schrander-Stumpel CT, Hofstra RM
J Med Genet 2010 Mar;47(3):169-75. Epub 2009 Oct 20 doi: 10.1136/jmg.2009.071688. PMID: 19846429

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