MedGen

Individuals with 22q11.2 deletion syndrome (22q11.2DS) can present with a wide range of features that are highly variable, even within families. The major clinical manifestations of 22q11.2DS include congenital heart disease, particularly conotruncal malformations (ventricular septal defect, tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus), palatal abnormalities (velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate), immune deficiency, characteristic facial features, and learning difficulties. Hearing loss can be sensorineural and/or conductive. Laryngotracheoesophageal, gastrointestinal, ophthalmologic, central nervous system, skeletal, and genitourinary anomalies also occur. Psychiatric illness and autoimmune disorders are more common in individuals with 22q11.2DS. [from GeneReviews]

Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. Attacks typically start in the abdomen with low-grade pain that slowly increases over a period of days (not hours) with nausea progressing to vomiting. In some individuals, the pain is predominantly in the back or extremities. When an acute attack is untreated, a motor neuropathy may develop over a period of days or a few weeks. The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Some individuals experience respiratory insufficiency due to loss of innervation of the diaphragm and muscles of respiration. Acute attacks are associated commonly with use of certain medications, caloric deprivation, and changes in female reproductive hormones. About 20% of those with an acute attack also experience photosensitivity associated with bullae and skin fragility. [from GeneReviews]

Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course. [from GeneReviews]

Parkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.

Often the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.

Parkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.

Generally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease. [from MedlinePlus Genetics]

Lipoid proteinosis (LP) is characterized by deposition of hyaline-like material in various tissues resulting in a hoarse voice from early infancy, vesicles and hemorrhagic crusts in the mouth and on the face and extremities, verrucous and keratotic cutaneous lesions on extensor surfaces (especially the elbows), and moniliform blepharosis (multiple beaded papules along the eyelid margins and inner canthus). Extracutaneous manifestations may include epilepsy, neuropsychiatric disorders, spontaneous CNS hemorrhage, and asymptomatic multiple yellowish nodules throughout the gastrointestinal tract. Generally, the disease course is chronic and fluctuating. Males and females are affected equally. Affected individuals have a normal life span unless they experience laryngeal obstruction. [from GeneReviews]

Progressive myoclonic epilepsy-10 (EPM10) is an autosomal recessive neurodegenerative disorder characterized by onset of progressive myoclonus, ataxia, spasticity, dysarthria, and cognitive decline in the first decade of life. The severity is variable, but some patients may become mute and bedridden with psychosis (summary by Turnbull et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). [from OMIM]

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the IMPA1 gene. [from MONDO]

An inappropriate feeling of being persecuted or being the subject of hostility from others. [from HPO]