Phenotypes associated with the disease Multiple congenital anomalies-hypotonia-seizures syndrome (ORPHA:280633):
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:280633)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:280633)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:280633)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:280633)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:280633)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Hoarse cry (HP:0001615). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Short foot (HP:0001773): A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- 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: Frequent (HP:0040282). (ORPHA:280633)
- Macrocephaly at birth (HP:0004488): The presence of an abnormally large skull with onset at birth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Prominent palatine ridges (HP:0010291): Increased size and/or number of soft tissue folds on the palatal side of the maxillary alveolar ridge. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Prominent superior crus of antihelix (HP:0011247): Increased protrusion of the superior crus relative to the prominence of a normal antihelix stem. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:280633)
- Hydrocele testis (HP:0000034): Accumulation of clear fluid in the between the layers of membrane (tunica vaginalis) surrounding the testis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hydroureter (HP:0000072): The distention of the ureter with urine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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:280633)
- Gingival overgrowth (HP:0000212): Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Prominent occiput (HP:0000269): Increased convexity of the occiput (posterior part of the skull). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Small forehead (HP:0000350): The presence of a forehead that is abnormally small. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Overfolded helix (HP:0000396): A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Blepharitis (HP:0000498): Inflammation of the eyelids. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Amblyopia (HP:0000646): Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Narrow chest (HP:0000774): Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Abnormal posterior cranial fossa morphology (HP:0000932): An abnormality of the fossa cranii posterior (the posterior fossa), which is made up primarily of the occipital bone and which surrounds to the foramen magnum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Right ventricular hypertrophy (HP:0001667): In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hypoplastic fingernail (HP:0001804): Underdevelopment of a fingernail. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Anal stenosis (HP:0002025): Abnormal narrowing of the anal opening. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Pulmonary arterial hypertension (HP:0002092): Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Recurrent aspiration pneumonia (HP:0002100): Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Large fleshy ears (HP:0002265). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Fair hair (HP:0002286): A lesser degree of hair pigmentation than would otherwise be expected. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Partial absence of cerebellar vermis (HP:0002951): Congenital absence of a part of the vermis of cerebellum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Short nose (HP:0003196): 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: Occasional (HP:0040283). (ORPHA:280633)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Deep longitudinal plantar crease (HP:0004681): Narrow, paramedian longitudinal depressions in the plantar skin of the forefoot. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Abnormal renal collecting system morphology (HP:0004742): An abnormality of the renal collecting system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Peripheral pulmonary artery stenosis (HP:0004969): Stenosis of a peripheral branch of the pulmonary artery. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Flexion contracture of toe (HP:0005830): One or more bent (flexed) toe joints that cannot be straightened actively or passively. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Proportionate shortening of all digits (HP:0006165). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Elevated circulating alpha-fetoprotein concentration (HP:0006254): The concentration of alpha-fetoprotein in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Hyperpigmented/hypopigmented macules (HP:0007441). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Microtia (HP:0008551): Underdevelopment of the external ear. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Urinary bladder wall hypertrophy (HP:0008635): Increase in thickness of the wall of the urinary bladder. This finding may be seen in conditions such as bladder outlet obstruction and may be accompanied by increased trabeculation of the bladder wall musculature. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Congenital megaureter (HP:0008676): A developmental disturbance with extreme ureteral dilatation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Unilateral renal dysplasia (HP:0008718): A unilateral form of developmental dysplasia of the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Proximal lower limb muscle weakness (HP:0008994): A lack of strength of the proximal muscles of the legs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Thin lower lip vermilion (HP:0010282): Height of the vermilion of the medial part of the lower lip more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the lower lip in the frontal view (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Vertical nystagmus (HP:0010544): Vertical nystagmus may present with either up-beating or down-beating eye movements or both. When present in the straight-ahead position of gaze it is referred to as upbeat nystagmus or downbeat nystagmus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Increased nuchal translucency (HP:0010880): Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Prominent tragus (HP:0011271): Increase posterolateral protrusion of the tragus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Asymmetric crying face (HP:0011333): Asymmetry observed in the face of a neonate or infant whose face appears symmetric at rest and asymmetric during crying as the mouth is pulled downward on one side while not moving on the other side. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)
- Rectovestibular fistula (HP:0025025): A congenital malformation characterized by an abnormal connection (fistula) between the rectum and the vulval vestibule, at the lower aspect of the vaginal opening. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:280633)