Phenotypes associated with the disease Nijmegen breakage syndrome (OMIM:251260):
- Anal stenosis (HP:0002025): Abnormal narrowing of the anal opening. Evidence: IEA. (OMIM:251260)
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 2/11. (PMID:7545870)
- Premature ovarian insufficiency (HP:0008209): Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian insuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea. Evidence: IEA. (OMIM:251260)
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: IEA. (OMIM:251260)
- Short stature (HP:0004322): 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. (OMIM:251260)
- Autoimmune hemolytic anemia (HP:0001890): An autoimmune form of hemolytic anemia. Evidence: TAS. (OMIM:251260)
- 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: PCS. Frequency: 1/1. (PMID:19635536)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 0/1. (PMID:19635536)
- Neurodegeneration (HP:0002180): Progressive loss of neural cells and tissue. Evidence: IEA. (OMIM:251260)
- Cafe-au-lait spot (HP:0000957): Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children. Evidence: PCS. (PMID:22373003)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Chromosome breakage (HP:0040012): Elevated rate of chromosomal breakage or interchanges occurring either spontaneously or following exposure to various DNA-damaging agents. This feature may be assayed by treatment of cultured lymphocytes with agents such as chemical mutagens, irradiation, and alkylating agents. Evidence: PCS. Frequency: 3/3. (PMID:32843899;PMID:38761025;PMID:19635536)
- 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: PCS. Frequency: 1/1. (PMID:19635536)
- T-cell lymphoma (HP:0012190): A type of lymphoma that originates in T-cells. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Decreased total lymphocyte count (HP:0001888): A reduced number of lymphocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Rhabdomyosarcoma (HP:0002859). Evidence: IEA. (OMIM:251260)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: IEA. (OMIM:251260)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 2/2. (PMID:38761025;PMID:19635536)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: IEA. (OMIM:251260)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Progressive vitiligo (HP:0005602). Evidence: IEA. (OMIM:251260)
- 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: IEA. (OMIM:251260)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 11/11. Onset: Congenital onset (HP:0003577). (PMID:7545870)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: PCS. Frequency: 3/11. (PMID:7545870)
- Choanal atresia (HP:0000453): Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral. Evidence: PCS. (PMID:22373003)
- Bronchiectasis (HP:0002110): Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways. Evidence: PCS. Frequency: 2/11. (PMID:7545870)
- 2-3 toe syndactyly (HP:0004691): Syndactyly with fusion of toes two and three. Evidence: PCS. Frequency: 5/11. (PMID:7545870)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Telangiectasia of the skin (HP:0100585): Presence of small, permanently dilated blood vessels near the surface of the skin, visible as small focal red lesions. Evidence: PCS. Frequency: 0/1. (PMID:19635536)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 2/2. (PMID:38761025;PMID:19635536)
- Prominent nose (HP:0000448): Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:22373003)
- Conjunctival telangiectasia (HP:0000524): The presence of small (ca. 0.5-1.0 mm) dilated blood vessels near the surface of the mucous membranes of the conjunctiva. Evidence: PCS. Frequency: 5/11. (PMID:7545870)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 2/11. (PMID:7545870)
- Glioma (HP:0009733): The presence of a glioma, which is a neoplasm of the central nervous system originating from a glial cell (astrocytes or oligodendrocytes). Evidence: IEA. (OMIM:251260)
- 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: PCS. Frequency: 13/13. (PMID:32843899;PMID:7545870;PMID:19635536)
- Sandal gap (HP:0001852): A widely spaced gap between the first toe (the great toe) and the second toe. Evidence: PCS. Frequency: 7/11. (PMID:7545870)
- Sinusitis (HP:0000246): Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction. Evidence: IEA. (OMIM:251260)
- Cleft upper lip (HP:0000204): A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development. Evidence: IEA. (OMIM:251260)
- Lymphoma (HP:0002665): A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells. Evidence: IEA. (OMIM:251260)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: IEA. (OMIM:251260)
- Increased total leukocyte count (HP:0001974): An abnormal increase in the number of leukocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 11/11. (PMID:22373003;PMID:19635536)
- Decreased circulating IgE concentration (HP:0005479): An abnormally decreased level of immunoglobulin E (IgE) in blood. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Retinal pigment epithelial mottling (HP:0007814): Mottling (spots or blotches of different shades) of the retinal pigment epithelium, i.e., localized or generalized fundus pigment granularity associated with processes at the level of the retinal pigment epithelium. Evidence: PCS. Frequency: 2/11. (PMID:7545870)
- 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: PCS. Frequency: 23/23. (PMID:32843899;PMID:22373003;PMID:38761025;PMID:7545870)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 12/12. (PMID:38761025;PMID:7545870)
- Long philtrum (HP:0000343): 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: PCS. Frequency: 2/2. (PMID:38761025;PMID:19635536)
- Deep philtrum (HP:0002002): Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border. Evidence: PCS. Frequency: 2/11. (PMID:7545870)
- Mastoiditis (HP:0000265): Infection of the mastoid air cells, arising as a complication of otitis media or occurring in the context of unusual susceptibility to infection. Evidence: IEA. (OMIM:251260)
- Malar prominence (HP:0010620): Prominence of the malar process of the maxilla and infraorbital area appreciated in profile and from in front of the face. Evidence: IEA. (OMIM:251260)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 0/2. (PMID:38761025;PMID:19635536)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Recurrent bronchitis (HP:0002837): An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis. Evidence: PCS. Frequency: 6/11. (PMID:7545870)
- High palate (HP:0000218): 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: PCS. Frequency: 1/1. (PMID:38761025)
- Recurrent pneumonia (HP:0006532): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 6/11. (PMID:7545870)
- Decreased circulating IgM concentration (HP:0002850): An abnormally decreased level of immunoglobulin M (IgM) in blood. Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Decreased total T cell count (HP:0005403): Abnormal decrease in the absolute number of T cells, commonly characterized as CD3+ lymphocytes, per microliter of blood, compared to a reference range for a given sex and age-group. These may include both TCR alpha/beta and gamma/delta T cells. Evidence: TAS. (OMIM:251260)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: TAS. (OMIM:251260)
- Recurrent infection of the gastrointestinal tract (HP:0004798): Recurrent infection of the gastrointestinal tract. Evidence: TAS. (OMIM:251260)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 10/11. (PMID:22373003;PMID:19635536)
- Long nose (HP:0003189): Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base. Evidence: PCS. (PMID:22373003)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Abnormal circulating IgG concentration (HP:0410242): An abnormal deviation from normal levels of IgG immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:19635536)
- Abnormal circulating IgM concentration (HP:0410243): An abnormal deviation from normal levels of IgM immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:19635536)
- Thickened helices (HP:0000391): Increased thickness of the helix of the ear. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Pneumonia (HP:0002090): Inflammation of any part of the lung parenchyma. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Decreased total B cell count (HP:0010976): The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group. Evidence: TAS. (OMIM:251260)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/1. (PMID:38761025)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 1/1. (PMID:19635536)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 1/1. (PMID:32843899)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:251260)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: PCS. Frequency: 2/2. (PMID:38761025;PMID:19635536)
- Medulloblastoma (HP:0002885): A rapidly growing embryonic tumor arising in the posterior part of the cerebellar vermis and neuroepithelial roof of the fourth ventricle in children. More rarely, medulloblastoma arises in the cerebellum in adults. Evidence: IEA. (OMIM:251260)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 11/11. (PMID:7545870)