MedGen

Intellectual developmental disorder with language impairment and early-onset dopa-responsive dystonia-parkinsonism (IDLDP) is a neurodevelopmental disorder characterized by global developmental delay affecting motor, cognitive, and speech domains apparent in early childhood or infancy. Some patients may have normal early development in infancy before symptom onset. There is phenotypic heterogeneity and the severity is highly variable; less severely affected individuals have only mild deficits and are able to attend special schools. About half of patients develop various types of seizures that may be refractory or responsive to treatment. Most patients also show movement abnormalities, often hypotonia early in the disease course with later development of dopa-responsive dystonia or parkinsonism (Ramos et al., 2019, Wirth et al., 2020; Singh et al., 2020). [from OMIM]

Immunodeficiency-42 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to mycobacterial and candidal infections beginning in infancy. Patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections (summary by Okada et al., 2015). [from OMIM]

Susceptibility to idiopathic generalized epilepsy-15 (EIG15) is an autosomal dominant seizure disorder characterized by onset of variable types of seizures in the first decade. Absence seizures are the most common manifestation, but most patients also develop other types, including clonic or generalized tonic-clonic seizures. EEG tends to show 3-Hz spike-wave discharges, whereas brain imaging is normal. The majority of patients also have developmental delay associated with impaired intellectual development apparent from infancy or early childhood (summary by Rudolf et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see EIG (600669). [from OMIM]

Ovarian dysgenesis-8 (ODG8) is characterized by complete lack of estrogen action, resulting in absent breast development, primary amenorrhea, and osteoporosis (Lang-Muritano et al., 2018). For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300). [from OMIM]

Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency. [from GeneReviews]

Progressive familial intrahepatic cholestasis-5 (PFIC5) is an autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy (summary by Gomez-Ospina et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600). [from OMIM]

Obesity associated with an identifiable mutation in a single gene. [from NCI]

Any Fanconi syndrome in which the cause of the disease is a mutation in the HNF4A gene. [from MONDO]

The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating.

Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin. Insulin is a hormone that helps control levels of blood glucose, also called blood sugar. People with this condition have frequent episodes of low blood glucose (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma. [from MedlinePlus Genetics]

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disorder characterized by delayed development, moderately impaired intellectual development, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by Bosch et al., 2014). [from OMIM]

Syndromic microphthalmia-12 is a rare disease characterized by bilateral small eyeballs (microphthalmia), lungs that are too small (pulmonary hypoplasia), and a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity (diaphragmatic hernia). Other symptoms may include: Severe global developmental delay with progressive motor impairment due to spasticity and/or uncontrolled repetitive muscular contractions (dystonia), with or without abnormal quick movements that resemble dancing (chorea), Defects of the cerebellum (Chiari type I malformation) Accumulation of cerebrospinal fluid inside the brain (hydrocephaly), Severe feeding difficulties, Mild facial dysmorphism with broad nasal root and tip, and a very small chin (micrognathia), Severe language delay, Wheelchair-bound. Syndromic microphthalmia-12 is caused by mutations in the RARB gene. There is no specific treatment for this syndrome. [from MONDO]

Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994). [from OMIM]

A rare, autosomal recessive inherited disorder usually caused by mutations in the THRB gene. It is characterized by a defective physiological resistance to thyroid hormones, resulting in the elevation of thyroxin and triiodothyronine in the serum. [from MONDO]

Any hypothyroidism, congenital, nongoitrous in which the cause of the disease is a mutation in the THRA gene. [from MONDO]

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.

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.

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 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. [from MedlinePlus Genetics]

Any azoospermia in which the cause of the disease is a mutation in the NR5A1 gene. [from MONDO]

Generalized thyroid hormone resistance is characterized by elevated serum levels of free thyroid hormones with inappropriately elevated thyroid-stimulating hormone (TSH) as well as clinical and biochemical evidence of decreased thyroid hormone action. Affected individuals also show unresponsiveness to large doses of exogenous thyroid hormones (summary by Parrilla et al., 1991). [from OMIM]

Any primary ovarian failure in which the cause of the disease is a mutation in the NR5A1 gene. [from MONDO]