MedGen

PRRT2-associated paroxysmal movement disorders (PRRT2-PxMD) include paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC), and hemiplegic migraine (HM). In addition, PRRT2 pathogenic variants have been identified in other childhood-onset movement disorders and different types of seizures, suggesting that the understanding of the spectrum of PRRT2-PxMD is still evolving. The paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and less commonly ballismus. The seizures of BFIE are usually focal with or without generalization. Thirty percent of PRRT2-associated PKD is associated with BFIE and is referred to as PKD/IC. [from GeneReviews]

PRRT2-associated paroxysmal movement disorders (PRRT2-PxMD) include paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC), and hemiplegic migraine (HM). In addition, PRRT2 pathogenic variants have been identified in other childhood-onset movement disorders and different types of seizures, suggesting that the understanding of the spectrum of PRRT2-PxMD is still evolving. The paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and less commonly ballismus. The seizures of BFIE are usually focal with or without generalization. Thirty percent of PRRT2-associated PKD is associated with BFIE and is referred to as PKD/IC. [from GeneReviews]

Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). [from OMIM]

The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212). [from OMIM]

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by clusters of nocturnal motor seizures, which are often stereotyped and brief (5 seconds to 5 minutes). They vary from simple arousals from sleep to dramatic, often bizarre hyperkinetic events with tonic or dystonic features. Affected individuals may experience aura. Retained awareness during seizures is common. A minority of individuals experience daytime seizures. Onset ranges from infancy to adulthood. About 80% of individuals develop ADNFLE in the first two decades of life; mean age of onset is ten years. Clinical neurologic examination is normal and intellect is usually preserved, but reduced intellect, psychiatric comorbidity, or cognitive deficits may occur. Within a family, the manifestations of the disorder may vary considerably. ADNFLE is lifelong but not progressive. As an individual reaches middle age, attacks may become milder and less frequent. [from GeneReviews]

Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles). Signs and symptoms of mitochondrial complex III deficiency usually begin in infancy but can appear later.

The severity of mitochondrial complex III deficiency varies widely among affected individuals. People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). More severely affected individuals have problems with multiple body systems, such as liver disease that can lead to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty with communication. Some affected individuals have a form of heart disease called cardiomyopathy, which can lead to heart failure. 

Most people with mitochondrial complex III deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis). Some affected individuals also have buildup of molecules called ketones (ketoacidosis) or high blood glucose levels (hyperglycemia). Abnormally high levels of these chemicals in the body can be life-threatening.

Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood. [from MedlinePlus Genetics]

IMD38 predisposes individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines (Bogunovic et al., 2012). Patients do not experience severe disease in response to viral infection. Affected individuals have intracranial calcification (Zhang et al., 2015). [from OMIM]

Benign familial infantile seizures (BFIS) is a seizure disorder of early childhood with age at onset from 3 months up to 24 months. It is characterized by brief seizures beginning with slow deviation of the head and eyes to 1 side and progressing to generalized motor arrest and hypotonia, apnea and cyanosis, and limb jerks. Seizures usually occur in clusters over a day or several days. The ictal EEG shows focal parietal-temporal activity, whereas the interictal EEG is normal. Concurrent and subsequent psychomotor and neurologic development are normal (Franzoni et al., 2005). See also benign familial neonatal seizures (BFNS1; 121200). Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm. Genetic Heterogeneity of Benign Familial Infantile Seizures The BFIS1 locus has been mapped to chromosome 19q. BFIS2 (605751) is caused by mutation in the PRRT2 gene on chromosome 16p11. BFIS3 (607745), which is caused by the mutations in the SCN2A gene (182390) on chromosome 2q24, has a slightly earlier age at onset and is sometimes termed benign familial 'neonatal-infantile' seizures. BFIS4 (612627) has been mapped to chromosome 1p. BFIS5 (617080) is caused by mutation in the SCN8A gene (600702) on chromosome 12q13. BFIS6 (see 610353) is caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21. [from OMIM]

A deviation from normal of the neurological development of a child, which may include any or all of the aspects of the development of personal, social, gross or fine motor, and cognitive abilities. [from HPO]