- Absent septum pellucidum (HP:0001331): Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- Preaxial hand polydactyly (HP:0001177): Supernumerary digits located at the radial side of the hand. Polydactyly (supernumerary digits) involving the thumb occurs in many distinct forms of high variability and severity. Ranging from fleshy nubbins over varying degrees of partial duplication/splitting to completely duplicated or even triplicated thumbs or preaxial (on the radial side of the hand) supernumerary digits. Evidence: PCS. Frequency: 0/6. (PMID:33776626;PMID:25105228;PMID:26706854)
- Cavum septum pellucidum (HP:0002389): If the two laminae of the septum pellucidum are not fused then a fluid-filled space or cavum is present. The cavum septum pellucidum is present at birth but usually obliterates by the age of 3 to 6 months. It is up to 1cm in width and the walls are parallel. It is an enclosed space and is not part of the ventricular system or connected with the subarachnoid space. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- Submucous cleft soft palate (HP:0011819): A cleft of the muscular (soft) portion of the palate that is covered by mucous membrane. Soft-palate submucous clefts are characterized by a midline deficiency or lack of muscle tissue. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- 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. (OMIM:603671)
- Midline defect of the nose (HP:0004122): This term groups together three conditions that presumably represent different degrees of severity of a midline defect of the nose or nasal tip. Evidence: PCS. Frequency: 4/4. (PMID:25105228)
- Upper airway obstruction (HP:0002781): Increased resistance to the passage of air in the upper airway. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:603671)
- 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: 2/4. (PMID:26706854)
- Onychogryphosis (HP:0001805): Onychogryphosis is a disorder of nail plate growth that is clinically characterized by an opaque, yellow-brown thickening of the nail plate with associated gross hyperkeratosis, elongation, and increased curvature. Evidence: IEA. (OMIM:603671)
- 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: 9/9. (PMID:33776626;PMID:25105228;PMID:26706854)
- Preaxial foot polydactyly (HP:0001841): Duplication of all or part of the first ray. Evidence: PCS. Frequency: 5/6. (PMID:33776626;PMID:25105228;PMID:26706854)
- Retrocerebellar cyst (HP:0006951). Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- 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:603671)
- 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: 1/4. (PMID:25105228)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 3/4. (PMID:26706854)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- Bifid nose (HP:0011803): Visually assessable vertical indentation, cleft, or depression of the nasal bridge, ridge and tip. Evidence: PCS. Frequency: 8/9. (PMID:33776626;PMID:25105228;PMID:26706854)
- 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: 6/7. (PMID:25105228;PMID:26706854)
- Calcification of falx cerebri (HP:0005462): The presence of calcium deposition in the falx cerebri. Evidence: PCS. Frequency: 3/4. (PMID:25105228)
- Hypopituitarism (HP:0040075). Evidence: PCS. Frequency: 2/3. (PMID:25105228)
- Vertical clivus (HP:0010559): An abnormal vertical orientation of the clivus (which normally forms a kind of slope from the sella turcica down to the region of the foramen magnum). Evidence: PCS. Frequency: 4/4. (PMID:25105228)
- Choroid plexus cyst (HP:0002190): A cyst occurring within the choroid plexus within a cerebral ventricle. Evidence: PCS. Frequency: 2/4. (PMID:25105228)
- Optic nerve hypoplasia (HP:0000609): Underdevelopment of the optic nerve. Evidence: PCS. Frequency: 1/3. (PMID:25105228)
- Late first trimester onset (HP:0034199): This term refers to a phenotypic feature that was first observed prior to birth in the first trimester during the early fetal period, which is defined as 11 0/7 to 13 6/7 weeks of gestation (inclusive). Evidence: PCS. Frequency: 1/1. (PMID:33776626)
- Short tibia (HP:0005736): Underdevelopment (reduced size) of the tibia. Evidence: PCS. Frequency: 3/4. (PMID:25105228)
- 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:25105228)
- 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: IEA. (OMIM:603671)
- 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:603671)
- 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: PCS. Frequency: 1/9. (PMID:33776626;PMID:25105228;PMID:26706854)
- Midline central nervous system lipomas (HP:0006866). Evidence: PCS. Frequency: 6/8. (PMID:25105228;PMID:26706854)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 8/8. (PMID:25105228;PMID:26706854)
- Persistent falcine venous sinus (HP:6000295): A falcine sinus that does not involute but persists beyond birth is defined as a persistent falcine sinus. In the 20-mm embryo stage, the primitive falx cerebri contains the sagittal plexus, a meshwork of anastomotic venous channels from which the superior sagittal sinus and straight sinus are thought to develop. A persistent falcine sinus represents a persistent channel of the caudal anastomotic loops of the sagittal plexus. Evidence: TAS. (OMIM:603671)
- 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: 1/5. (PMID:33776626;PMID:25105228)
- Encephalocele (HP:0002084): A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. Evidence: PCS. Frequency: 11/19. (PMID:33776626;OMIM:603671;PMID:25105228;PMID:26706854)
- Gray matter heterotopia (HP:0002282): Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter. Evidence: IEA. (OMIM:603671)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/4. (PMID:25105228)
- Midline facial cleft (HP:0100629): A congenital malformation with a cleft (gap or opening) in the midline of the face. Evidence: PCS. Frequency: 5/5. (PMID:25105228;PMID:26706854)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: IEA. (OMIM:603671)
- Bifid nasal tip (HP:0000456): A splitting of the nasal tip. Visually assessable vertical indentation, cleft, or depression of the nasal tip. Evidence: IEA. (OMIM:603671)
- Parietal foramina (HP:0002697): The presence of symmetrical and circular openings (foramina) in the parietal bone ranging in size from a few millimeters to several centimeters wide. Evidence: PCS. Frequency: 4/8. (PMID:25105228;PMID:26706854)
- Remnants of the hyaloid vascular system (HP:0007968): Persistence of the hyaloid artery, which is the embryonic artery that runs from the optic disc to the posterior lens capsule may persist; the site of attachment may form an opacity. The hyaloid artery is a branch of the ophthalmic artery, and usually regresses completely before birth. This features results from a failure of regression of the hyaloid vessel, which supplies the primary vitreous during embryogenesis and normally regresses in the third trimester of pregnancy, leading to a particular form of posterior cataract. Evidence: PCS. Frequency: 1/3. (PMID:25105228)
- 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: 12/14. (OMIM:603671;PMID:26706854)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 4/4. (PMID:26706854)
- Large sella turcica (HP:0002690): An abnormal enlargement of the sella turcica. Evidence: PCS. Frequency: 3/4. (PMID:25105228)
- Patellar hypoplasia (HP:0003065): Underdevelopment of the patella. Evidence: PCS. Frequency: 3/3. (PMID:25105228)
- Periventricular nodular heterotopia (HP:0032388): Nodules of heterotopia along the ventricular walls. There can be a single nodule or a large number of nodules, they can exist on either or both sides of the brain at any point along the higher ventricle margins, they can be small or large, single or multiple. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- Aplasia of the olfactory bulb (HP:0032466): Lack of formation (congenital absence) of the olfactory bulb. Evidence: PCS. Frequency: 2/2. (PMID:25105228)
- Basilar artery fenestration (HP:6000787): A fenestration affecting the basilar artery. Basilar fenestration typically occurs at the lower end of the basilar artery just as the vertebral arteries join Fenestrations of intracranial arteries are segmental duplications of the lumen into two distinct endothelium-lined channels, which may or may not share their adventitial layer. They can range from a small focus of divided tissue to long-segment duplication. Fenestrations are the result of partial failure of fusion of paired primitive embryologic vessels or incomplete obliteration of different anastomosis in a primitive vascular network. The association of fenestrations with aneurysms has been suggested in many small case series, though the exact relationship is not well defined. Evidence: TAS. (OMIM:603671)
- Dilation of Virchow-Robin spaces (HP:0012520): Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery. Evidence: PCS. Frequency: 1/4. (PMID:25105228)
- Telecanthus (HP:0000506): Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi. Evidence: PCS. Frequency: 4/4. (PMID:25105228)
- Tubulonodular pericallosal lipoma (HP:0034014): A type of pericallosal lipoma with a rounded or lobular appearance and a diameter that is usually above 2 cm. They are anteriorly situated and are associated with extensive callosal and often fronto-facial anomalies. A tubulonodular pericallosal lipoma can extend into the choroid plexus or lateral ventricles. Evidence: PCS. Frequency: 4/4. (PMID:25105228)
- 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: 5/8. (PMID:25105228;PMID:26706854)
- Absent fetal nasal bone (HP:0025706): The nasal bone is considered absent when it is not visualized on a midsagittal view of the profile. In the second trimester, a true midsagittal view of the fetal profile is obtained and magnified to fill the majority of the image space. The nasal bone appears as an echogenic linear structure below the skin edge. The optimal angle of insonation is 45 degrees to the longitudinal axis of the fetal nasal bone. If the angle of insonation is 0 or 180 degrees, the nasal bone may appear artificially absent. The presence or absence of the nasal bone may be determined at the time of the 11- to 14-week ultrasound examination and used as part of the risk assessment for aneuploidy. Evidence: PCS. Frequency: 1/1. (PMID:33776626)
- 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:603671)
- 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: 2/4. (PMID:25105228;PMID:26706854)
- Glaucoma (HP:0000501): Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure. Evidence: PCS. Frequency: 1/3. (PMID:25105228)
- Mesomelic leg shortening (HP:0004987): Shortening of the middle parts of the leg in relation to the upper and terminal segments. Evidence: PCS. Frequency: 1/1. (PMID:33776626)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: PCS. Frequency: 2/3. (PMID:25105228)
These phenotypes are associated with the disease acromelic frontonasal dysostosis (OMIM:603671).