- Carious teeth (HP:0000670): 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). (ORPHA:79408)
- Fragile skin (HP:0001030): Skin that splits easily with minimal injury. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Milia (HP:0001056): Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Atrophic scars (HP:0001075): Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- 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: Very frequent (HP:0040281). (ORPHA:79408)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Mitten deformity (HP:0004057): Fusion of the hands and feet by a thin membrane of skin (scarring) seen in forms of dystrophic epidermolysis bullosa and leading to a "mitten" hand deformity. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Gastrointestinal inflammation (HP:0004386): Inflammation of the alimentary part of the gastrointestinal system. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Abnormal blistering of the skin (HP:0008066): The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Chronic pain (HP:0012532): Persistent pain, usually defined as pain that has lasted longer than 3 to 6 months. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Oral mucosal blisters (HP:0200097): Blisters arising in the mouth. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79408)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Anonychia (HP:0001798): Aplasia of the nail. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Iron deficiency anemia (HP:0001891). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Abnormal scalp morphology (HP:0001965): Any anomaly of the scalp, the skin an subcutaneous tissue of the head on which head hair grows. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Squamous cell carcinoma (HP:0002860): The presence of squamous cell carcinoma of the skin. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Nail dystrophy (HP:0008404): Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Generalized abnormality of skin (HP:0011354): An abnormality of the skin that is not localized to any one particular region. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Erosion of oral mucosa (HP:0031446): Loss of the superficial layer of the oral mucosa usually resulting in a shallow or crusted lesion. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Chronic cutaneous wound (HP:0032676): A cutaneous wound that has failed to proceed through the orderly and timely process to produce an atomic and functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79408)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Glomerulonephritis (HP:0000099): Inflammation of the renal glomeruli. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- IgA deposition in the glomerulus (HP:0000794): The presence of immunoglobulin A deposits in the glomerulus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Delayed puberty (HP:0000823): Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- 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:79408)
- 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:79408)
- Aplasia cutis congenita (HP:0001057): A developmental defect resulting in the congenital absence of skin in multiple or solitary non-inflammatory, well-demarcated, oval or circular ulcers with a diameter of about 1 to 2 cm. Aplasia cutis congenita most commonly occurs on the scalp, but may present in the face, trunk, or limbs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Recurrent skin infections (HP:0001581): Infections of the skin that happen multiple times. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Renal amyloidosis (HP:0001917): A form of amyloidosis that affects the kidney. On hematoxylin and eosin stain, amyloid is identified as extracellular amorphous material that is lightly eosinophilic. These deposits often stain weakly for periodic acid Schiff (PAS), demonstrate a blue-to-gray hue on the trichrome stain and are typically negative on the Jones methenamine silver (JMS) stain. These tinctorial properties contrast with the histologic appearance of collagen, a major component of basement membranes, mesangial matrix and areas of sclerosis, which demonstrates strong positivity for PAS and JMS (See Figure 1 of PMID:25852856). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Urinary bladder sphincter dysfunction (HP:0002839): Abnormal function of a sphincter of the urinary bladder. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Malnutrition (HP:0004395): A deficiency in the intake of energy and nutrients. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Esophageal ulceration (HP:0004791): Defect in the epithelium of the esophagus, essentially an open sore in the lining of the esophagus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Foot joint contracture (HP:0008366): Contractures of one or more joints of the feet meaning chronic loss of joint motion due to structural changes in non-bony tissue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Ankyloglossia (HP:0010296): Short or anteriorly attached lingual frenulum, associated with limited mobility of the tongue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Decreased plasma total carnitine (HP:0011936): A decreased concentration of total carnitine in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Cutaneous melanoma (HP:0012056): The presence of a melanoma of the skin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Urethral stricture (HP:0012227): Narrowing of the urethra associated with inflammation or scar tissue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Anal fissure (HP:0012390): A small tear in the thin, moist tissue (mucosa) that lines the anus. It appears as a crack or slit in the mucous membrane of the anus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Chronic kidney disease (HP:0012622): Functional anomaly of the kidney persisting for at least three months. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Decreased serum zinc (HP:0031831): A reduced concentration of zinc in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Abnormal circulating selenium concentration (HP:0031903): Any deviation from the normal circulating concentration of selenium. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Abnormality of vitamin metabolism (HP:0100508): An anomaly in the metabolism of a vitamin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Decreased circulating vitamin D concentration (HP:0100512): The concentration of vitamin D in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Corneal erosion (HP:0200020): An erosion or abrasion of the cornea's outermost layer of epithelial cells. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79408)
- Abnormality of the urinary system (HP:0000079): An abnormality of the urinary system. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79408)
- Genital blistering (HP:0031464): The presence of one or more bullae on the skin of the genital region, defined as fluid-filled blisters more than 5 mm in diameter with thin walls. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79408)
These phenotypes are associated with the disease Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form (ORPHA:79408).
The following phenotypes are NOT associated with this disease:
- Palmoplantar keratoderma (HP:0000982): Abnormal thickening of the skin of the palms of the hands and the soles of the feet. Evidence: TAS. (ORPHA:79408)
- Basal cell carcinoma (HP:0002671): The presence of a basal cell carcinoma of the skin. Evidence: TAS. (ORPHA:79408)
- Enamel hypoplasia (HP:0006297): Developmental hypoplasia of the dental enamel. Evidence: TAS. (ORPHA:79408)
- Abnormal respiratory system morphology (HP:0012252): A structural anomaly of the respiratory system. Evidence: TAS. (ORPHA:79408)