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X-linked complicated corpus callosum dysgenesis

MedGen UID:
374339
Concept ID:
C1839909
Disease or Syndrome
Synonym: Corpus callosum, partial agenesis of, X-linked
SNOMED CT: X-linked complicated corpus callosum dysgenesis (1010630006)
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): L1CAM (Xq28)
 
Monarch Initiative: MONDO:0010569
OMIM®: 304100
Orphanet: ORPHA1497

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

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Dislocated radial head
MedGen UID:
488814
Concept ID:
C0265563
Congenital Abnormality
A dislocation of the head of the radius from its socket in the elbow joint.
Aganglionic megacolon
MedGen UID:
5559
Concept ID:
C0019569
Disease or Syndrome
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. Genetic Heterogeneity of Hirschsprung Disease Several additional loci for isolated Hirschsprung disease have been mapped. HSCR2 (600155) is associated with variation in the EDNRB gene (131244) on 13q22; HSCR3 (613711) is associated with variation in the GDNF gene (600837) on 5p13; HSCR4 (613712) is associated with variation in the EDN3 gene (131242) on 20q13; HSCR5 (600156) maps to 9q31; HSCR6 (606874) maps to 3p21; HSCR7 (606875) maps to 19q12; HSCR8 (608462) maps to 16q23; and HSCR9 (611644) maps to 4q31-q32. HSCR also occurs as a feature of several syndromes including the Waardenburg-Shah syndrome (277580), Mowat-Wilson syndrome (235730), Goldberg-Shprintzen syndrome (609460), and congenital central hypoventilation syndrome (CCHS; 209880). Whereas mendelian modes of inheritance have been described for syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance. The development of surgical procedures decreased mortality and morbidity, which allowed the emergence of familial cases. HSCR occurs as an isolated trait in 70% of patients, is associated with chromosomal anomaly in 12% of cases, and occurs with additional congenital anomalies in 18% of cases (summary by Amiel et al., 2008).
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Partial agenesis of the corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
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.
Interhemispheric cyst
MedGen UID:
339924
Concept ID:
C1853188
Disease or Syndrome
Cystic collection (sac-like, fluid containing pocket of membranous tissue) located in the interhemispheric fissure, with or without communication with the ventricular system.
Inferior cerebellar vermis hypoplasia
MedGen UID:
343328
Concept ID:
C1855350
Congenital Abnormality
Underdevelopment of the inferior portion of the vermis of cerebellum.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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).
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked complicated corpus callosum dysgenesis
Follow this link to review classifications for X-linked complicated corpus callosum dysgenesis in Orphanet.

Professional guidelines

PubMed

Fransen E, Van Camp G, D'Hooge R, Vits L, Willems PJ
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Recent clinical studies

Etiology

Horlenko O, Lenchenko A, Kossey G, Tomey A, Debretseni O
Georgian Med News 2018 Dec;(285):47-51. PMID: 30702069
Guadagni MG, Faggella A, Piana G, D'Alessandro G
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Rosser TL, Acosta MT, Packer RJ
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Am J Med Genet 1995 May 22;57(1):107-16. doi: 10.1002/ajmg.1320570122. PMID: 7645588

Diagnosis

Schrauwen I, Szelinger S, Siniard AL, Corneveaux JJ, Kurdoglu A, Richholt R, De Both M, Malenica I, Swaminathan S, Rangasamy S, Kulkarni N, Bernes S, Buchhalter J, Ramsey K, Craig DW, Narayanan V, Huentelman MJ
Invest Ophthalmol Vis Sci 2015 Jun;56(6):3896-904. doi: 10.1167/iovs.14-16261. PMID: 26091538
Bahi-Buisson N, Guerrini R
Handb Clin Neurol 2013;111:653-65. doi: 10.1016/B978-0-444-52891-9.00068-3. PMID: 23622213
Guadagni MG, Faggella A, Piana G, D'Alessandro G
Eur J Paediatr Dent 2010 Sep;11(3):146-8. PMID: 21080756
Rosser TL, Acosta MT, Packer RJ
Pediatr Neurol 2002 Nov;27(5):343-6. doi: 10.1016/s0887-8994(02)00450-2. PMID: 12504201
Fransen E, Lemmon V, Van Camp G, Vits L, Coucke P, Willems PJ
Eur J Hum Genet 1995;3(5):273-84. doi: 10.1159/000472311. PMID: 8556302

Therapy

Horlenko O, Lenchenko A, Kossey G, Tomey A, Debretseni O
Georgian Med News 2018 Dec;(285):47-51. PMID: 30702069
Guadagni MG, Faggella A, Piana G, D'Alessandro G
Eur J Paediatr Dent 2010 Sep;11(3):146-8. PMID: 21080756
Rosser TL, Acosta MT, Packer RJ
Pediatr Neurol 2002 Nov;27(5):343-6. doi: 10.1016/s0887-8994(02)00450-2. PMID: 12504201

Prognosis

Gupta B, Ramteke P, Paul VK, Kumar T, DAS P
Turk Patoloji Derg 2019;35(2):162-165. doi: 10.5146/tjpath.2017.01391. PMID: 28272686
Bayram E, Topcu Y, Akinci G, Hiz S, Cakmakci H
Ann Saudi Med 2013 Jan-Feb;33(1):73-5. doi: 10.5144/0256-4947.2012.01.7.1545. PMID: 22750766Free PMC Article
Kato M, Dobyns WB
J Child Neurol 2005 Apr;20(4):392-7. doi: 10.1177/08830738050200042001. PMID: 15921244
Rosser TL, Acosta MT, Packer RJ
Pediatr Neurol 2002 Nov;27(5):343-6. doi: 10.1016/s0887-8994(02)00450-2. PMID: 12504201
Aftimos S, McGaughran J
Am J Med Genet 2001 Jan 22;98(3):273-6. doi: 10.1002/1096-8628(20010122)98:3<273::aid-ajmg1081>3.0.co;2-4. PMID: 11169567

Clinical prediction guides

Dunn P, Prigatano GP, Szelinger S, Roth J, Siniard AL, Claasen AM, Richholt RF, De Both M, Corneveaux JJ, Moskowitz AM, Balak C, Piras IS, Russell M, Courtright AL, Belnap N, Rangasamy S, Ramsey K, Opitz JM, Craig DW, Narayanan V, Huentelman MJ, Schrauwen I
Am J Med Genet A 2017 Mar;173(3):611-617. Epub 2017 Jan 31 doi: 10.1002/ajmg.a.38069. PMID: 28139025
Bayram E, Topcu Y, Akinci G, Hiz S, Cakmakci H
Ann Saudi Med 2013 Jan-Feb;33(1):73-5. doi: 10.5144/0256-4947.2012.01.7.1545. PMID: 22750766Free PMC Article
Vilain C, Mortier G, Van Vliet G, Dubourg C, Heinrichs C, de Silva D, Verloes A, Baumann C
Am J Med Genet A 2009 Jul;149A(7):1476-81. doi: 10.1002/ajmg.a.32678. PMID: 19504604
Rosser TL, Acosta MT, Packer RJ
Pediatr Neurol 2002 Nov;27(5):343-6. doi: 10.1016/s0887-8994(02)00450-2. PMID: 12504201
Proud VK, Levine C, Carpenter NJ
Am J Med Genet 1992 Apr 15-May 1;43(1-2):458-66. doi: 10.1002/ajmg.1320430169. PMID: 1605226

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