<unk>  presents as a spectrum ranging from mild to severe features. There is a genotype -phenotype correlation across the<unk>  spectrum, meaning that the specific genetic variant causing an<unk> -spectrum disorder in a patient determines the severity of the<unk>  in that patient. Patients with truncating (loss-of-function) variants in<unk> CAM, which prevent the full synthesis of<unk>  (protein) experience more severe features than patients with missense variants in<unk> CAM, which may result in an abnormal protein but do not prevent its synthesis. Illustrating this difference in<unk>  severity, up to 50% of infants born with<unk>  caused by a truncating mutation will die before the age of 3 years despite provision of best available medical treatment. In comparison, roughly 10% of infants born with<unk>  caused by a missense mutation will die before the age of 3 years. Despite its presentation on a continuous spectrum,<unk>  is loosely divided into four discrete phenotypes. Societal Implications Based on Symptoms People diagnosed with<unk>  often experience issues with respect to societal roles and interactions due to the severe physical and mental disabilities associated with the disorder. These issues can vary depending on the symptoms that manifest in a specific individual and the severity of those symptoms, which is ultimately determined based on where the individual is situated on the<unk>  spectrum. Spasticity is one of the most common signs of<unk>  and is seen in all four major clinical phenotypes. It is characterized as the continuous contraction of certain muscles, leading to muscle stiffness which can interfere with normal movement and speech. In three of the major phenotypes (except HSAS), this spasticity is presented as spastic paraplegia, where the muscles of the lower limbs are stiff and continuously contracted. This spastic paraplegia often manifests itself as a gait (walking motion) disorder, specifically shuffling gait in MASA syndrome patients, which acts as a source of handicap and stress due to postural instability, and leads to poor quality of life and increased mortality. Aphasia is also a common disorder, especially in people with MASA syndrome (a disorder on the<unk>  spectrum) and describes a range of language impairments with respect to syntax (structure), semantics (meaning), phonology (sound), morphology (structure), and/or pragmatics in language comprehension or expression. People with aphasia, as well as their family members, often experience a poor quality of life due to the social isolation and depression caused by this language impairment and therefore may seek therapy to enable functional and socially relevant communication. Therapy services to address aphasia in MASA syndrome patients include one-on-one sessions with a clinician, group therapy, or even computer-based therapy, which is becoming more popular given its accessibility. Intellectual disabilities also contribute to the social difficulties faced by people with<unk> , and can range from mild to severe depending on the person's location on the<unk>  spectrum. People with mild intellectual disability usually have an IQ around 50-70 (100 is the average) and are slower in all developmental areas, but they have no unusual physical characteristics and are able to blend in socially. Moderate intellectual disability characteristics include being able to maintain self-care with some support from other, travel to familiar places in the community, communicate in simple ways, and having an IQ around 35–50. Severe intellectual disability is often seen in people with X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) (on the<unk>  spectrum) and has several key characteristics including: the ability to understand speech but otherwise having very limited communication skills; the ability to learn daily routines and simple self-care, but need direct supervision in social settings and need family support to live in a supervised home setting. Depending on the severity of the intellectual disability, people with<unk>  will have varying levels of difficulty in adapting to their social environments and may need considerable support from others to complete day-to-day tasks. X-linked hydrocephalus with stenosis of the aqueduct of Sylvius aqueduct of Sylvius (cerebral aqueduct) highlighted in red within the skull. In X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), this aqueduct is abnormally narrow, leading to accumulation of excess cerebrospinal fluid (CSF) within the brain's ventricular system. X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) is the most severe phenotype on the<unk>  spectrum and is predominantly known for its major feature: profound hydrocephalus, typically beginning before birth. Due to its prenatal onset (i.e. before the bones of the skull have fused together), hydrocephalus associated with HSAS results in progressive macrocephaly (abnormal enlargement of the skull) due to markedly increased intracranial pressure. The signs and symptoms of hydrocephalus can vary depending on severity and age of onset, however irritability (due to pain) and vomiting are common amongst infants with the condition. Without treatment, congenital hydrocephalus can be fatal in infancy. In less severe cases of untreated hydrocephalus, a child may progress beyond infancy but often experiences nausea and vomiting, missed developmental milestones (both physical and cognitive/social), diplopia (double vision), and papilledema (swelling of the optic disc) which can progress to permanent visual impairment due to increased intracranial pressure if definitive treatment is withheld. Neurological damage, caused by both hydrocephalus and poor neuronal development because of defects in the<unk>  cell adhesion molecule, results in nearly all people with HSAS experiencing severe intellectual disability. People living with HSAS will also frequently experience spasticity, a condition causing some muscles to be continuously contracted, thereby causing stiffness of the body and challenges with walking and speaking. Spasticity is also known to cause difficulty in performing activities of daily living such as bathing and showering, dressing, and self-feeding. Despite HSAS frequently being considered an isolated disorder of the central nervous system, its genetic basis also causes musculoskeletal defects that result in more than half of males with HSAS displaying thumbs that are adducted (clasped, or brought inwards towards the palm). Specifically, this abnormal presentation of the hand is due to congenital malformations in the extensor pollicis brevis and/or extensor pollicis longus muscle of forearm. MASA syndrome MASA syndrome is named after its four principle features: mental retardation, adducted thumbs (clasped, or brought inwards towards the palm), shuffling gait, and aphasia (a language disability affecting the comprehension and production of speech as well as reading and writing abilities.
L1 syndrome
TAR syndrome
ATR-16 syndrome
Kufor–Rakeb syndrome
Irlen syndrome
Andersen–Tawil syndrome
MEDNIK syndrome
CAMFAK syndrome