Phenotypes associated with the disease Amish lethal microcephaly (ORPHA:99742):
- Cleft soft palate (HP:0000185): Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Sloping forehead (HP:0000340): Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Lissencephaly (HP:0001339): A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Limitation of joint mobility (HP:0001376): A reduction in the freedom of movement of one or more joints. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Organic aciduria (HP:0001992): Excretion of non-amino organic acids in urine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Spina bifida (HP:0002414): Incomplete closure of the embryonic neural tube, whereby some vertebral arches remain unfused and open. The mildest form is spina bifida occulta, followed by meningocele and meningomyelocele. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Limb hypertonia (HP:0002509). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Decreased skull ossification (HP:0004331): A reduction in the magnitude or amount of ossification of the skull. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:99742)
- Temperature instability (HP:0005968): Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:99742)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:99742)