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X-linked hydrocephalus syndrome(HYCX)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Aqueductal stenosis, X-linked; HYCX; HYDROCEPHALUS, CONGENITAL, X-LINKED; X-linked hydrocephalus; X-Linked Hydrocephalus with Stenosis of the Aqueduct of Sylvius
SNOMED CT: X-linked hydrocephalus syndrome (71779008); Bickers-Adams syndrome (71779008); X-linked hydrocephalus (71779008)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
Concept ID:
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:0010611
OMIM®: 307000
Orphanet: ORPHA2182

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]
Connie Stumpel  |  Yvonne J Vos   view full author information

Additional descriptions

The X-linked recessive form of congenital hydrocephalus (HYCX) is the most common of the inherited forms of hydrocephalus. The phenotype consists of enlarged cerebral ventricles and mental retardation, and often includes spastic paraparesis and adducted thumbs. The most severe cases die pre- or perinatally with gross hydrocephalus and enlarged head circumference. Stenosis of the aqueduct of Sylvius is frequently associated with the disorder (Rosenthal et al., 1992). See HYC1 (236600) for a discussion of nonsyndromic autosomal recessive forms of hydrocephalus.  http://www.omim.org/entry/307000
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.

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.

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

Clinical features

From HPO
Thumb contracture
MedGen UID:
Concept ID:
Acquired Abnormality
Chronic loss of joint motion in the thumb due to structural changes in non-bony tissue. The term camptodactyly is used if the distal and/or proximal interphalangeal joints are affected.
Adducted thumb
MedGen UID:
Concept ID:
Congenital Abnormality
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
MedGen UID:
Concept ID:
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.
MedGen UID:
Concept ID:
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Spastic paraplegia
MedGen UID:
Concept ID:
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Corpus callosum, agenesis of
MedGen UID:
Concept ID:
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Absent septum pellucidum
MedGen UID:
Concept ID:
Congenital Abnormality
Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm.
Corticospinal tract hypoplasia
MedGen UID:
Concept ID:
Intellectual disability
MedGen UID:
Concept ID:
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.
MedGen UID:
Concept ID:
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for X-linked hydrocephalus syndrome in Orphanet.

Professional guidelines


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

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