- Delayed closure of the anterior fontanelle (HP:0001476, a Human Phenotype Ontology term): A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life. Evidence: TAS. Frequency: Obligate (HP:0040280, a Human Phenotype Ontology term). (ORPHA:357074)
- High palate (HP:0000218, a Human Phenotype Ontology term): 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). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Progressive microcephaly (HP:0000253, a Human Phenotype Ontology term): Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Malar flattening (HP:0000272, a Human Phenotype Ontology term): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Hypertelorism (HP:0000316, a Human Phenotype Ontology term): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Smooth philtrum (HP:0000319, a Human Phenotype Ontology term): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Long philtrum (HP:0000343, a Human Phenotype Ontology term): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Low-set ears (HP:0000369, a Human Phenotype Ontology term): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Broad nasal tip (HP:0000455, a Human Phenotype Ontology term): Increase in width of the nasal tip. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Anteverted nares (HP:0000463, a Human Phenotype Ontology term): 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). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Downslanted palpebral fissures (HP:0000494, a Human Phenotype Ontology term): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Carious teeth (HP:0000670, a Human Phenotype Ontology term): Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Dementia (HP:0000726, a Human Phenotype Ontology term): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Delayed speech and language development (HP:0000750, a Human Phenotype Ontology term): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Cutis laxa (HP:0000973, a Human Phenotype Ontology term): Wrinkled, redundant, inelastic and sagging skin. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Global developmental delay (HP:0001263, a Human Phenotype Ontology term): 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. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Motor delay (HP:0001270, a Human Phenotype Ontology term): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Failure to thrive (HP:0001508, a Human Phenotype Ontology term): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Intrauterine growth retardation (HP:0001511, a Human Phenotype Ontology term): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Redundant skin (HP:0001582, a Human Phenotype Ontology term): Loose and sagging skin often associated with loss of skin elasticity. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Profound intellectual disability (HP:0002187, a Human Phenotype Ontology term): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Coarse hair (HP:0002208, a Human Phenotype Ontology term): Hair shafts are rough in texture. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Psychomotor deterioration (HP:0002361, a Human Phenotype Ontology term): Loss of previously present mental and motor abilities. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Poor speech (HP:0002465, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Generalized joint hypermobility (HP:0002761, a Human Phenotype Ontology term): Joint hypermobility (ability of a joint to move beyond its normal range of motion) affecting many or all joints of the body. In individuals with Joint hypermobility at multiple sites (usually five or more), the term generalized joint hypermobility is preferred. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Abnormal isoelectric focusing of serum transferrin (HP:0003160, a Human Phenotype Ontology term): Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Short nose (HP:0003196, a Human Phenotype Ontology term): Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Decreased muscle mass (HP:0003199, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Short stature (HP:0004322, a Human Phenotype Ontology term): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Prominent nasolabial fold (HP:0005272, a Human Phenotype Ontology term): Exaggerated bulkiness of the crease or fold of skin running from the lateral margin of the nose, where nasal base meets the skin of the face, to a point just lateral to the corner of the mouth (cheilion, or commissure). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Redundant neck skin (HP:0005989, a Human Phenotype Ontology term): Excess skin around the neck, often lying in horizontal folds. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Thick cerebral cortex (HP:0006891, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Excessive wrinkled skin (HP:0007392, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Prominent veins on trunk (HP:0007457, a Human Phenotype Ontology term): Prominent thoracic and abdominal veins. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Abnormal subcutaneous fat tissue distribution (HP:0007552, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Sparse hair (HP:0008070, a Human Phenotype Ontology term): Reduced density of hairs. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Postnatal growth retardation (HP:0008897, a Human Phenotype Ontology term): Slow or limited growth after birth. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Floppy infant (HP:0008947, a Human Phenotype Ontology term): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Lipodystrophy (HP:0009125, a Human Phenotype Ontology term): Degenerative changes of the fat tissue. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- High myopia (HP:0011003, a Human Phenotype Ontology term): A severe form of myopia with greater than -6.00 diopters. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Feeding difficulties (HP:0011968, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Fragmented elastic fibers in the dermis (HP:0025167, a Human Phenotype Ontology term): Elastic fibers in the dermis exhibit an increased number of breaks associated with disorganization of the structure of the elastic fibers. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Thick hair (HP:0100874, a Human Phenotype Ontology term): Increased density of hairs, i.e., and elevated number of hairs per unit area. Evidence: TAS. Frequency: Very frequent (HP:0040281, a Human Phenotype Ontology term). (ORPHA:357074)
- Inguinal hernia (HP:0000023, a Human Phenotype Ontology term): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Strabismus (HP:0000486, a Human Phenotype Ontology term): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Seizure (HP:0001250, a Human Phenotype Ontology term): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Spasticity (HP:0001257, a Human Phenotype Ontology term): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Pachygyria (HP:0001302, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Dandy-Walker malformation (HP:0001305, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Cerebellar hypoplasia (HP:0001321, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Lissencephaly (HP:0001339, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Congenital hip dislocation (HP:0001374, a Human Phenotype Ontology term). Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Polymicrogyria (HP:0002126, a Human Phenotype Ontology term): 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, a Human Phenotype Ontology term). (ORPHA:357074)
- Abnormal circulating apolipoprotein concentration (HP:0025201, a Human Phenotype Ontology term): Any deviation from the normal concentration of apolipoprotein in the blood circulation. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Sub-retinal pigment epithelium haemorrhage (HP:0025244, a Human Phenotype Ontology term): An accumulation of blood located between the retinal pigment epithelium (RPE) and Bruch membrane. Evidence: TAS. Frequency: Frequent (HP:0040282, a Human Phenotype Ontology term). (ORPHA:357074)
- Abnormality of the intrinsic pathway (HP:0010989, a Human Phenotype Ontology term): An abnormality of the intrinsic pathway (also known as the contact activation pathway) of the coagulation cascade. Evidence: TAS. Frequency: Occasional (HP:0040283, a Human Phenotype Ontology term). (ORPHA:357074)
These phenotypes are associated with the disease Autosomal recessive cutis laxa type 2, classic type (ORPHA:357074, an Orphanet rare-disease identifier).
The following phenotypes are NOT associated with this disease:
- Emphysema (HP:0002097, a Human Phenotype Ontology term). Evidence: TAS. (ORPHA:357074)