- Pachygyria (HP:0001302): Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- 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:2671)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- Ichthyosis (HP:0008064): An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- Thick vermilion border (HP:0012471): Increased width of the skin of vermilion border region of upper lip. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- Abnormal nervous system morphology (HP:0012639): A structural anomaly of the nervous system. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- Lack of skin elasticity (HP:0100679). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:2671)
- Ambiguous genitalia (HP:0000062): A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale: Prader 0: Normal female external genitalia. Prader 1: Female external genitalia with clitoromegaly. Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus. Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening. Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus. Prader 5: Normal male external genitalia. The diagnosis of ambiguous genitalia is made for Prader 1-4. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Hypogonadism (HP:0000135): A decreased functionality of the gonad. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormality of the mouth (HP:0000153): An abnormality of the mouth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Trismus (HP:0000211): Limitation in the ability to open the mouth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Everted lower lip vermilion (HP:0000232): An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormality of the philtrum (HP:0000288): An abnormality of the philtrum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Depressed nasal ridge (HP:0000457): Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormality of the skin (HP:0000951): An abnormality of the skin. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Large hands (HP:0001176). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Pachygyria (HP:0001302): Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Dandy-Walker malformation (HP:0001305): A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Absent septum pellucidum (HP:0001331): Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- 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:2671)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Aplasia/Hypoplasia involving the skeletal musculature (HP:0001460): Absence or underdevelopment of the musculature. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Broad foot (HP:0001769): A foot for which the measured width is above the 95th centile for age; or, a foot that appears disproportionately wide for its length. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Polymicrogyria (HP:0002126): Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormality of neuronal migration (HP:0002269): An abnormality resulting from an anomaly of neuronal migration, i.e., of the process by which neurons travel from their origin to their final position in the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormal cerebellar vermis morphology (HP:0002334): An anomaly of the vermis of cerebellum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Abnormal cortical gyration (HP:0002536): An abnormality of the gyri (i.e., the ridges) of the cerebral cortex of the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- External genital hypoplasia (HP:0003241): Underdevelopment of part or all of the external reproductive organs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Muscle spasm (HP:0003394): Sudden and involuntary contractions of one or more muscles. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Muscular dystrophy (HP:0003560): The term dystrophy means abnormal growth. However, muscular dystrophy is used to describe primary myopathies with a genetic basis and a progressive course characterized by progressive skeletal muscle weakness and wasting, defects in muscle proteins, and histological features of muscle fiber degeneration (necrosis) and regeneration. If possible, it is preferred to use other HPO terms to describe the precise phenotypic abnormalities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:2671)
- Cleft palate (HP:0000175): Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Submucous cleft hard palate (HP:0000176): Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Prominent occiput (HP:0000269): Increased convexity of the occiput (posterior part of the skull). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Abnormal eyelid morphology (HP:0000492): An abnormality of the eyelids. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Abnormal eyelash morphology (HP:0000499): An abnormality of the eyelashes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Abnormal nasolacrimal system morphology (HP:0000614): An abnormality of the nasolacrimal drainage system, which serves as a conduit for tear flow from the external eye to the nasal cavity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- 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: Occasional (HP:0040283). (ORPHA:2671)
- Pterygium (HP:0001059): Pterygia are 'winglike' triangular membranes occurring in the neck, eyes, knees, elbows, ankles or digits. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Abnormal hair morphology (HP:0001595): An abnormality of the hair. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Pulmonary hypoplasia (HP:0002089). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- 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: Occasional (HP:0040283). (ORPHA:2671)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Rickets (HP:0002748): Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Osteomalacia (HP:0002749): Osteomalacia is a general term for bone weakness owing to a defect in mineralization of the protein framework known as osteoid. This defective mineralization is mainly caused by lack in vitamin D. Osteomalacia in children is known as rickets. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Micromelia (HP:0002983): The presence of abnormally small extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
- Abnormal cardiovascular system morphology (HP:0030680): Any structural anomaly of the heart and blood vessels. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:2671)
These phenotypes are associated with the disease Neu-Laxova syndrome (ORPHA:2671).