- 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: 4/25. (PMID:17546652;PMID:10942434)
- 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: 1/1. (PMID:17546652)
- Lens subluxation (HP:0001132): Partial dislocation of the lens of the eye. Evidence: PCS. Frequency: 11/33. (PMID:19160445;PMID:10942434;PMID:27259167;PMID:17975799)
- Gaze-evoked nystagmus (HP:0000640): Nystagmus made apparent by looking to the right or to the left. Evidence: PCS. Frequency: 1/1. (PMID:19160445)
- Pyloric stenosis (HP:0002021): Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss. Evidence: PCS. Frequency: 1/24. (PMID:10942434)
- 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: 1/12. (PMID:27259167)
- Slow pupillary light response (HP:0030211): Reduced velocity and acceleration in the pupillary light response. Evidence: PCS. (PMID:17975799)
- 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: 1/1. (PMID:19160445)
- Myoclonic seizure (HP:0032794): A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 1/1. (PMID:19160445)
- Duplicated collecting system (HP:0000081): A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice. Evidence: PCS. Frequency: 1/24. Onset: Congenital onset (HP:0003577). (PMID:10942434)
- Peripapillary atrophy (HP:0500087): Thinning in the layers of the retina and retinal pigment epithelium around the optic nerve. Evidence: PCS. Frequency: 2/2. (PMID:20799329)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 2/2. Onset: Infantile onset (HP:0003593). (PMID:20799329)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 3/5. (PMID:17975799)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:19160445)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- Developmental cataract (HP:0000519): A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens. Evidence: PCS. Frequency: 8/15. (PMID:10942434)
- 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: 1/24. Onset: Congenital onset (HP:0003577). (PMID:10942434)
- Attenuation of retinal blood vessels (HP:0007843): Narrowing of the retinal blood vessels, both arterioles and venules. Evidence: PCS. Frequency: 4/5. (PMID:17975799)
- 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: 1/1. (PMID:19160445)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- 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: 5/36. (PMID:10942434;PMID:27259167)
- 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: 1/12. (PMID:27259167)
- 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: 3/14. (PMID:10942434)
- High myopia (HP:0011003): A severe form of myopia with greater than -6.00 diopters. Evidence: PCS. Frequency: 30/31. (PMID:17546652;PMID:30007336;PMID:10942434;PMID:27259167;PMID:20799329)
- Cortical cataract (HP:0100019): A cataract which affects the layer of the lens surrounding the nucleus, i.e., the lens cortex. It is identified by its unique wedge or spoke appearance. Evidence: PCS. Frequency: 6/12. (PMID:27259167)
- 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:10942434)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/12. (PMID:27259167)
- 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:17546652)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 6/6. (PMID:17546652;PMID:17975799)
- Band keratopathy (HP:0000585): An abnormality of the cornea characterized by the deposition of calcium in a band across the central cornea, leading to decreased vision, foreign body sensation, and ocular irritation. Evidence: PCS. Frequency: 2/5. (PMID:17975799)
- Retinal detachment (HP:0000541): Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Evidence: PCS. Frequency: 18/28. (PMID:17546652;PMID:10942434;PMID:27259167)
- Persistent pupillary membrane (HP:0009917): The presence of remnants of a fetal membrane that persist as strands of tissue crossing the pupil. Evidence: PCS. Frequency: 3/12. (PMID:27259167)
- Bifid ureter (HP:0030037): Incomplete duplication of the ureter. Evidence: PCS. Frequency: 1/24. Onset: Congenital onset (HP:0003577). (PMID:10942434)
- Bifid ureter (HP:0030037): Incomplete duplication of the ureter. Evidence: PCS. Frequency: 1/12. (PMID:27259167)
- 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: PCS. Frequency: 1/1. (PMID:19160445)
- Spina bifida occulta (HP:0003298): The closed form of spina bifida with incomplete closure of a vertebral body with intact overlying skin. Evidence: PCS. Frequency: 2/24. Onset: Congenital onset (HP:0003577). (PMID:10942434)
- Iris transillumination defect (HP:0012805): Transmission of light through the iris as visualized upon slit lamp examination or infrared iris transillumination videography. The light passes through defects in the pigmentation of the iris. Evidence: PCS. Frequency: 5/12. (PMID:27259167)
- 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: 21/24. Onset: Congenital onset (HP:0003577). (PMID:10942434)
- 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: 1/2. (PMID:20799329)
- 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: 3/12. (PMID:27259167)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/2. (PMID:20799329)
- Occipital meningocele (HP:0002436): A herniation of meninges through a congenital bone defect in the skull in the occipital region. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- Macular hypoplasia (HP:0001104): Underdevelopment of the macula lutea. Evidence: PCS. Frequency: 2/2. (PMID:30007336)
- Chorioretinal atrophy (HP:0000533): Atrophy (wasting) of the choroid and retinal layers of the fundus. Evidence: PCS. Frequency: 21/21. (PMID:30007336;PMID:27259167;PMID:17975799;PMID:20799329)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:19160445)
- Renal duplication (HP:0000075): A congenital anomaly of the urinary tract, in which the kidney is duplicated and is drained via two separate renal pelves and ureters. Evidence: PCS. Frequency: 1/12. (PMID:27259167)
- Alopecia of scalp (HP:0002293). Evidence: PCS. Frequency: 1/12. (PMID:27259167)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/24. (PMID:10942434)
- Horizontal eyebrow (HP:0011228): An eyebrow that extends straight across the brow, without curve. Evidence: PCS. Frequency: 1/1. (PMID:17546652)
- 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: 1/24. (PMID:10942434)
- Phthisis bulbi (HP:0000667): Atrophy of the eyeball with blindness and decreased intraocular pressure due to end-stage intraocular disease. Evidence: PCS. (PMID:17975799)
- Vitreoretinopathy (HP:0007773): Ocular abnormality characterized by premature degeneration of the vitreous and the retina that may be associated with increased risk of retinal detachment. Evidence: PCS. Frequency: 18/20. (PMID:10942434;PMID:17975799)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 8/8. (PMID:17546652;PMID:17975799;PMID:20799329)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 2/4. (PMID:17975799)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 1/2. (PMID:17546652)
- 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: 1/1. (PMID:19160445)
- Polymicrogyria (HP:0002126): Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds). Evidence: PCS. Frequency: 4/13. (PMID:19160445;PMID:27259167)
These phenotypes are associated with the disease Knobloch syndrome 1 (OMIM:267750).