Phenotypes associated with the disease Kleefstra syndrome 1 (OMIM:610253):
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 7/7. (PMID:39013458)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 38/119. (PMID:39013458;PMID:19264732)
- Strabismus (HP:0000486): 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: PCS. Frequency: 24/76. (PMID:39013458)
- 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: PCS. Frequency: 10/111. (PMID:39013458)
- Seizure (HP:0001250): 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: PCS. Frequency: 18/18. (PMID:39013458)
- Protruding tongue (HP:0010808): Tongue extending beyond the alveolar ridges or teeth at rest. Evidence: PCS. Frequency: Frequent (HP:0040282). (PMID:20945554)
- 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: 49/125. Onset: Childhood onset (HP:0011463). (PMID:39013458)
- 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: PCS. Frequency: 29/114. (PMID:39013458)
- U-Shaped upper lip vermilion (HP:0010806): Gentle upward curve of the upper lip vermilion such that the center is placed well superior to the commissures. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Juvenile onset (HP:0003621). (PMID:20945554)
- 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: PCS. Frequency: 9/104. (PMID:39013458)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 27/104. (PMID:39013458)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 55/104. (PMID:39013458)
- 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: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: TAS. (OMIM:610253)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: PCS. Frequency: 2/110. (PMID:39013458)
- Sporadic (HP:0003745): Cases of the disease in question occur without a previous family history, i.e., as isolated cases without being transmitted from a parent and without other siblings being affected. Evidence: PCS. (PMID:20945554)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 30/125. (PMID:39013458)
- 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: PCS. Frequency: 112/125. (PMID:39013458)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 33/124. (PMID:39013458;PMID:19264732)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: PCS. Frequency: Frequent (HP:0040282). (PMID:20945554)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: PCS. Frequency: 6/115. (PMID:39013458)
- Tall stature (HP:0000098): A height above that which is expected according to age and gender norms. Evidence: PCS. Frequency: 8/111. (PMID:39013458)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 10/53. (PMID:39013458)
- Natal tooth (HP:0000695): A tooth present at birth or erupting within the first month of life. Evidence: PCS. Frequency: Occasional (HP:0040283). Onset: Congenital onset (HP:0003577). (PMID:20945554)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 31/38. (PMID:39013458)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 3/3. (PMID:39013458)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: PCS. Frequency: 30/125. (PMID:39013458)
- Global developmental delay (HP:0001263): 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: PCS. Frequency: 114/124. (PMID:39013458)
- 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. (PMID:20945554)
- Tube feeding (HP:0033454): Feeding problem necessitating food and nutrient delivery via a tube. Evidence: PCS. Frequency: 9/104. (PMID:39013458)
- Coronary artery fistula (HP:0011641): A congenital malformation with abnormal connection between one of the coronary arteries and a heart chamber or another blood vessel. Evidence: PCS. Frequency: 1/117. (PMID:39013458)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 8/125. (PMID:39013458)
- Umbilical hernia (HP:0001537): Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect. Evidence: PCS. Frequency: 2/125. (PMID:39013458)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: PCS. Frequency: 9/104. (PMID:39013458)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 3/125. (PMID:39013458)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 3/3. (PMID:39013458)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: PCS. Frequency: 1/115. (PMID:39013458)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:39013458)
- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Tracheobronchomalacia (HP:0002786): Weakness of the cartilage in the trachea and the bronchi, resulting in a floppy (non-rigid) airway. Affected persons may have difficulties to maintain patency of the airways. Evidence: PCS. Frequency: Very rare (HP:0040284). (PMID:20945554)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 2/115. (PMID:39013458)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: PCS. Frequency: 5/109. (PMID:39013458)
- 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: Frequent (HP:0040282). (PMID:20945554)
- Anteverted nares (HP:0000463): 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: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. (PMID:20945554)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: PCS. Frequency: 41/41. (PMID:39013458)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 4/115. (PMID:39013458)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: PCS. Frequency: 4/117. (PMID:39013458)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: Frequent (HP:0040282). (PMID:20945554)
- Flat face (HP:0012368): Absence of concavity or convexity of the face when viewed in profile. Evidence: PCS. (PMID:20945554)
- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: TAS. (OMIM:610253)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 52/56. (PMID:39013458)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 10/109. (PMID:39013458)
- 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: PCS. Frequency: 26/104. (PMID:39013458)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: PCS. Frequency: 59/119. (PMID:39013458)
- Atrioventricular canal defect (HP:0006695): A defect of the atrioventricular septum of the heart. Evidence: PCS. Frequency: 1/109. (PMID:39013458)
- Hallux valgus (HP:0001822): Lateral deviation of the great toe (i.e., in the direction of the little toe). Evidence: PCS. Frequency: 4/125. (PMID:39013458)
- Motor stereotypy (HP:0000733): Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose. Evidence: PCS. Frequency: 18/114. (PMID:20945554;PMID:39013458)
- Bipolar affective disorder (HP:0007302): Bipolar disorder is an illness of mood characterized by alternating episodes of elevated and depressed moods, which are interspersed with euthymic periods. Evidence: PCS. Frequency: 3/104. (PMID:39013458)
- Persistence of primary teeth (HP:0006335): Persistence of the primary teeth beyond the age by which they normally are shed and replaced by the permanent teeth. Evidence: PCS. Frequency: Occasional (HP:0040283). Onset: Juvenile onset (HP:0003621). (PMID:20945554)
- 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: Frequent (HP:0040282). (PMID:20945554)
- Large for gestational age (HP:0001520): The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age. Evidence: PCS. Frequency: 19/91. (PMID:39013458)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 0/84. (PMID:39013458)
- Talipes equinovarus (HP:0001762): Talipes equinovarus (also called clubfoot) typically has four main components: inversion and adduction of the forefoot; inversion of the heel and hindfoot; equinus (limitation of extension) of the ankle and subtalar joint; and internal rotation of the leg. Evidence: PCS. Frequency: 5/125. (PMID:39013458)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 35/125. (PMID:39013458)
- 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: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Febrile seizure (within the age range of 3 months to 6 years) (HP:0002373): A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years. Evidence: PCS. Frequency: 6/118. (PMID:39013458)
- Atonic seizure (HP:0010819): Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature. Evidence: PCS. Frequency: 2/117. (PMID:39013458)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Ureteropelvic junction obstruction (HP:0000074): Blockage of urine flow from the renal pelvis to the proximal ureter. Evidence: PCS. Frequency: 2/115. (PMID:39013458)
- Psychosis (HP:0000709): A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis. Evidence: PCS. Frequency: 14/104. (PMID:39013458)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 5/125. (PMID:39013458)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 12/92. (PMID:39013458)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: PCS. Frequency: 2/115. (PMID:39013458)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: PCS. Frequency: 1/117. (PMID:39013458)
- Overweight (HP:0025502): Increased body weight with a body mass index of 25-29.9 kg per square meter. Evidence: PCS. Frequency: 39/109. (PMID:39013458)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: PCS. Frequency: Very rare (HP:0040284). Onset: Juvenile onset (HP:0003621). (PMID:20945554)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: Frequent (HP:0040282). (PMID:20945554)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:20945554)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: PCS. Frequency: 16/23. (PMID:39013458)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: PCS. Frequency: 7/104. (PMID:39013458)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 2/115. (PMID:39013458)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: Frequent (HP:0040282). (PMID:20945554)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: Frequent (HP:0040282). Onset: Childhood onset (HP:0011463). (PMID:19264732)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: 13/109. (PMID:39013458)
- Conotruncal defect (HP:0001710): A congenital malformation of the outflow tract of the heart. Conotruncal defects are thought to result from a disturbance of the outflow tract of the embryonic heart, and comprise truncus arteriosus, tetralogy of Fallot, interrupted aortic arch, transposition of the great arteries, and double outlet right ventricle. Evidence: PCS. (PMID:20945554)
- Self-mutilation (HP:0000742): Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die. Evidence: PCS. Frequency: 10/104. (PMID:39013458)