Phenotypes associated with the disease Meckel syndrome, type 1 (OMIM:249000):
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: IEA. (OMIM:249000)
- Camptodactyly of finger (HP:0100490): The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- 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: 2/2. (PMID:27377014;PMID:33193692)
- Bile duct proliferation (HP:0001408): Proliferative changes of the bile ducts. Evidence: IEA. (OMIM:249000)
- 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:27377014)
- 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: IEA. (OMIM:249000)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: IEA. (OMIM:249000)
- Molar tooth sign on MRI (HP:0002419): An abnormal appearance of the midbrain in axial magnetic resonance imaging in which the elongated superior cerebellar peduncles give the midbrain an appearance reminiscent of a molar or wisdom tooth. Evidence: PCS. Frequency: 2/2. (PMID:27377014;PMID:33193692)
- Radial deviation of finger (HP:0009466): Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly. Evidence: IEA. (OMIM:249000)
- Vascular dilatation (HP:0002617): An abnormal increase in the diameter of an artery or vein, either as a diffuse dilatation or as a localized, sac-like outpouching of the vessel wall (aneurysm). Evidence: IEA. (OMIM:249000)
- Adrenal hypoplasia (HP:0000835): Developmental hypoplasia of the adrenal glands. Evidence: IEA. (OMIM:249000)
- Cerebral hypoplasia (HP:0006872): Underdevelopment of the cerebrum. Evidence: IEA. (OMIM:249000)
- Elevated amniotic fluid alpha-fetoprotein concentration (HP:0004639): An elevation of alpha-feto protein measured in the amniotic fluid. Evidence: TAS. (OMIM:249000)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- 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: IEA. (OMIM:249000)
- Polycystic kidney dysplasia (HP:0000113): The presence of multiple cysts in both kidneys. Evidence: PCS. Frequency: 5/5. (PMID:17377820)
- Abnormality of the larynx (HP:0001600): An abnormality of the larynx. Evidence: IEA. (OMIM:249000)
- 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: PCS. Frequency: 0/3. (PMID:35360848)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: IEA. (OMIM:249000)
- Olfactory lobe agenesis (HP:0001341). Evidence: IEA. (OMIM:249000)
- Rotary nystagmus (HP:0001583): A form of nystagmus in which the eyeball makes rotary motions around the axis. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Natal tooth (HP:0000695): A tooth present at birth or erupting within the first month of life. Evidence: IEA. (OMIM:249000)
- Dilated fourth ventricle (HP:0002198): An abnormal dilatation of the fourth cerebral ventricle. Evidence: PCS. Frequency: 3/3. (PMID:35360848)
- Hypoplasia of the bladder (HP:0005343): Underdevelopment of the urinary bladder. Evidence: IEA. (OMIM:249000)
- Abnormality of the uterus (HP:0000130): An abnormality of the uterus. Evidence: IEA. (OMIM:249000)
- 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: 2/2. (PMID:27377014;PMID:33193692)
- External genital hypoplasia (HP:0003241): Underdevelopment of part or all of the external reproductive organs. Evidence: IEA. (OMIM:249000)
- Postaxial polydactyly (HP:0100259): A form of polydactyly in which the extra digit or digits are localized on the side of the fifth finger or fifth toe. Evidence: PCS. Frequency: 3/3. (PMID:35360848)
- Second trimester onset (HP:0034198): This term refers to a phenotypic feature that was first observed prior to birth during the second trimester, which comprises the range of gestational ages from 14 0/7 weeks to 27 6/7 (inclusive). Evidence: PCS. Frequency: 4/4. (PMID:27377014;PMID:35360848)
- Chiari malformation (HP:0002308): Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow. Evidence: IEA. (OMIM:249000)
- Cystic renal dysplasia (HP:0000800). Evidence: PCS. Frequency: 0/3. (PMID:35360848)
- 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:17377820)
- Hypotelorism (HP:0000601): Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes). Evidence: IEA. (OMIM:249000)
- Microphthalmia (HP:0000568): A developmental anomaly characterized by abnormal smallness of one or both eyes. Evidence: IEA. (OMIM:249000)
- Enlarged naris (HP:0009931): Increased aperture of the nostril. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Large placenta (HP:0006267): Increased size of the placenta. Evidence: IEA. (OMIM:249000)
- Omphalocele (HP:0001539): A midline anterior incomplete closure of the abdominal wall in which there is herniation of the abdominal viscera into the base of the abdominal cord. Evidence: IEA. (OMIM:249000)
- 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: PCS. Frequency: 0/3. (PMID:35360848)
- Low-set ears (HP:0000369): 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: IEA. (OMIM:249000)
- Abnormal cardiac septum morphology (HP:0001671): An anomaly of the intra-atrial or intraventricular septum. Evidence: IEA. (OMIM:249000)
- Anencephaly (HP:0002323): Anencephaly is a developmental anomaly characterized by a fetus that has no calvarium, with a lack of most or all of the fetus' brain tissue. Anencephaly belongs to a collective group known as neural tube defects (NTD) and is a result of the neural tube failing to close in its rostral end during fetal development. Evidence: IEA. (OMIM:249000)
- 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: IEA. (OMIM:249000)
- Pulmonary hypoplasia (HP:0002089). Evidence: IEA. (OMIM:249000)
- Single umbilical artery (HP:0001195): Single umbilical artery (SUA) is the absence of one of the two umbilical arteries surrounding the fetal bladder and in the fetal umbilical cord. Evidence: IEA. (OMIM:249000)
- Ambiguous genitalia, female (HP:0000061): Ambiguous genitalia in an individual with XX genetic gender. Evidence: IEA. (OMIM:249000)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: PCS. Frequency: 4/4. (PMID:27377014;PMID:35360848)
- Occipital encephalocele (HP:0002085): A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp. Evidence: PCS. Frequency: 9/9. (PMID:35360848;PMID:17377820)
- Lobulated tongue (HP:0000180): Multiple indentations and/or elevations on the edge and/or surface of the tongue producing an irregular surface contour. Evidence: IEA. (OMIM:249000)
- Foot polydactyly (HP:0001829): A kind of polydactyly characterized by the presence of a supernumerary toe or toes. Evidence: IEA. (OMIM:249000)
- Asplenia (HP:0001746): Absence (aplasia) of the spleen. Evidence: IEA. (OMIM:249000)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Dandy-Walker malformation (HP:0001305): 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: IEA. (OMIM:249000)
- Iris coloboma (HP:0000612): A coloboma of the iris. Evidence: IEA. (OMIM:249000)
- 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: PCS. Frequency: 1/1. (PMID:27377014)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Accessory spleen (HP:0001747): An accessory spleen is a round, iso-echogenic, homogenic and smooth structure and is seen as a normal variant mostly on the medial contour of the spleen, near the hilus or around the lower pole. This has no pathogenic relevance. Evidence: IEA. (OMIM:249000)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: TAS. (OMIM:249000)
- Epicanthus inversus (HP:0000537): A fold of skin starting at or just below the medial aspect of the lower lid and arching upward to cover, extend in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Breech presentation (HP:0001623): A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first. Evidence: IEA. (OMIM:249000)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:249000)
- Ambiguous genitalia, male (HP:0000033): Ambiguous genitalia in an individual with XY genetic gender. Evidence: IEA. (OMIM:249000)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: IEA. (OMIM:249000)
- 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: IEA. (OMIM:249000)
- Talipes (HP:0001883): A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus. Evidence: IEA. (OMIM:249000)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: IEA. (OMIM:249000)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Postaxial hand polydactyly (HP:0001162): Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger). Evidence: PCS. Frequency: 4/6. (PMID:17377820;PMID:33193692)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: IEA. (OMIM:249000)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: IEA. (OMIM:249000)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. Frequency: 1/1. (PMID:27377014)
- Malformation of the hepatic ductal plate (HP:0006563). Evidence: PCS. Frequency: 1/1. (PMID:17377820)
- Bowing of the long bones (HP:0006487): A bending or abnormal curvature of a long bone. Evidence: IEA. (OMIM:249000)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: IEA. (OMIM:249000)
- Postaxial foot polydactyly (HP:0001830): Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit. Evidence: PCS. Frequency: 5/5. (PMID:17377820)
- Syndactyly (HP:0001159): Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism". Evidence: IEA. (OMIM:249000)
- Abnormality of the ureter (HP:0000069): An abnormality of the ureter. The ureter is the duct by which urine passes from the kidney to the bladder. Evidence: IEA. (OMIM:249000)
- Webbed neck (HP:0000465): Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline. Evidence: IEA. (OMIM:249000)
- 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: IEA. (OMIM:249000)
- Intestinal malrotation (HP:0002566): An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis. Evidence: IEA. (OMIM:249000)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: IEA. (OMIM:249000)
- Renal agenesis (HP:0000104): Agenesis, that is, failure of the kidney to develop during embryogenesis and development. Evidence: IEA. (OMIM:249000)