The presence of leiomyoma of the skin.

An increased concentration of an amino acid in the urine.

The concentration of succinate in the urine, normalized for urine concentration, is above the upper limit of normal.

The concentration of fumaric acid in the urine, normalized for urine concentration, is above the upper limit of normal.

A ventricular septal defect that is confluent with and involves the membranous septum and is bordered by an atrioventricular valve, not including the type 3 VSDs.

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Accumulation of fluid in the peritoneal cavity.

Impairment of bile flow due to obstruction in the small bile ducts within the liver.

A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.

Inflammation of the intestine leading to bacterial invasion causing cellular damage and death which causes necrosis of the colon and intestine.

Abnormalities in the sound of a person's speech or vocalization are not necessarily associated with a known physical cause or due to stuttering or stammering.

Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.

The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

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.

Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).

A cyst occurring within the choroid plexus within a cerebral ventricle.

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Underdevelopment of the brainstem.

Underdevelopment of the operculum.

Profound mental retardation is defined as an intelligence quotient (IQ) below 20.

An increase in size of the ventricular system of the brain.

Polycythemia is diagnosed if the red blood cell count, the hemoglobin level, and the red blood cell volume all exceed the upper limits of normal.

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.

Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.

A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.

A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.

Generalized muscular hypotonia (abnormally low muscle tone).

Head circumference below 2 standard deviations below the mean for age and gender.

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

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.

An increased amount of bilirubin in the blood.

An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of fumarate hydratase activity.

Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).

Conjunctival icterus is a condition where there is yellowing of the whites of the eyes. This is most commonly seen in patients who have liver disease.

Posterior positioning of the nasal root in relation to the overall facial profile for age.

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Abnormally pale skin.

The presence of excess amniotic fluid in the uterus during pregnancy.

A bilateral form of fetal pyelectasis.

Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

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.

Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

The mitochondrial matrix refers to the substance occupying the space enclosed by the inner membrane of a mitochondrion, which contains enzymes, DNA, granules, and inclusions of protein crystals, glycogen, and lipid. Mitochondrial swelling refers to an increase in size of the mitochondrial matrix. This phenomenon is thought to be related to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix. Mitochondrial swelling may distend the outer membrane until it ruptures.