- Brachyturricephaly (HP:0000244): Abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region. Evidence: IEA. (OMIM:214100)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 4/4. (PMID:34513757;PMID:28446956)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: IEA. (OMIM:214100)
- Focal clonic seizure (HP:0002266): A focal clonic seizure is a type of focal motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Focal impaired awareness seizure (HP:0002384): Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Decreased muscle mass (HP:0003199). Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/2. (PMID:34513757)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:214100)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: IEA. (OMIM:214100)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/2. (PMID:28446956)
- Albuminuria (HP:0012592): Increased concentration of albumin in the urine. Evidence: TAS. (OMIM:214100)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- Subependymal cysts (HP:0002416): Cerebral cysts, usually located in the wall of the caudate nucleus or in the caudothalamic groove. They are found in up to 5.2% of all neonates, using transfontanellar ultrasound in the first days of life. Evidence: IEA. (OMIM:214100)
- Metatarsus adductus (HP:0001840): The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body. Evidence: IEA. (OMIM:214100)
- Abnormal electroretinogram (HP:0000512): Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography. Evidence: IEA. (OMIM:214100)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: IEA. (OMIM:214100)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: IEA. (OMIM:214100)
- 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:9398848)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: TAS. (OMIM:214100)
- Partial agenesis of the corpus callosum (HP:0001338): A partial failure of the development of the corpus callosum. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- 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: 2/2. (PMID:21844578;PMID:33708531)
- Weak cry (HP:0001612). Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: IEA. (OMIM:214100)
- Elevated circulating long chain fatty acid concentration (HP:0003455): Increased concentration of long-chain fatty acids in the blood circulation. Evidence: PCS. Frequency: 3/3. (PMID:34513757;PMID:21844578)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- 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: IEA. (OMIM:214100)
- Pulmonary hypoplasia (HP:0002089). Evidence: IEA. (OMIM:214100)
- 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: IEA. (OMIM:214100)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/1. Onset: Infantile onset (HP:0003593). (PMID:28446956)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: IEA. (OMIM:214100)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- Tongue fasciculations (HP:0001308): Fasciculations or fibrillation affecting the tongue muscle. Evidence: PCS. Frequency: 0/1. (PMID:21844578)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Fetal distress (HP:0025116): An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- 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: IEA. (OMIM:214100)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 1/2. (PMID:34513757)
- Redundant neck skin (HP:0005989): Excess skin around the neck, often lying in horizontal folds. Evidence: IEA. (OMIM:214100)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: IEA. (OMIM:214100)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/2. (PMID:34513757)
- 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: 2/2. (PMID:34513757)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:214100)
- 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: PCS. Frequency: 1/1. (PMID:33708531)
- Epiphyseal stippling (HP:0010655): The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses. Evidence: IEA. (OMIM:214100)
- Aplasia/Hypoplasia of the corpus callosum (HP:0007370): Absence or underdevelopment of the corpus callosum. Evidence: IEA. (OMIM:214100)
- Rocker bottom foot (HP:0001838): The presence of both a prominent heel and a convex contour of the sole. Evidence: IEA. (OMIM:214100)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: IEA. (OMIM:214100)
- Glaucoma (HP:0000501): Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure. Evidence: IEA. (OMIM:214100)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Neonatal respiratory distress (HP:0002643): Respiratory difficulty as newborn. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- 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: 1/1. (PMID:21844578)
- 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: IEA. (OMIM:214100)
- Opacification of the corneal stroma (HP:0007759): Reduced transparency of the stroma of cornea. Evidence: IEA. (OMIM:214100)
- 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: 2/4. (PMID:34513757;PMID:28446956)
- Protruding tongue (HP:0010808): Tongue extending beyond the alveolar ridges or teeth at rest. Evidence: TAS. (OMIM:214100)
- 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:21844578;PMID:33708531)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- 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: 1/1. (PMID:33708531)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Adrenal hypoplasia (HP:0000835): Developmental hypoplasia of the adrenal glands. Evidence: IEA. (OMIM:214100)
- Intrahepatic biliary dysgenesis (HP:0001401). Evidence: IEA. (OMIM:214100)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: IEA. (OMIM:214100)
- 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: 1/1. (PMID:33708531)
- Round face (HP:0000311): The facial appearance is more circular than usual as viewed from the front. Evidence: IEA. (OMIM:214100)
- 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:214100)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Flat occiput (HP:0005469): Reduced convexity of the occiput (posterior part of skull). Evidence: IEA. (OMIM:214100)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. (OMIM:214100)
- 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: 1/1. (PMID:21844578)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: IEA. (OMIM:214100)
- 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: 1/1. (PMID:33708531)
- 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: 4/4. (PMID:34513757;PMID:28446956)
- Widely patent fontanelles and sutures (HP:0004492): An abnormally increased width of the cranial fontanelles and sutures. Evidence: IEA. (OMIM:214100)
- Ankle clonus (HP:0011448): Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Hyperbilirubinemia (HP:0002904): An increased amount of bilirubin in the blood. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- Bilateral single transverse palmar creases (HP:0007598): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease on both hands. Evidence: PCS. Frequency: 1/1. (PMID:33708531)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/2. (PMID:28446956)
- 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: IEA. (OMIM:214100)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Triangular face (HP:0000325): Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Bell-shaped thorax (HP:0001591): The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter. Evidence: IEA. (OMIM:214100)
- Wide anterior fontanel (HP:0000260): Enlargement of the anterior fontanelle with respect to age-dependent norms. Evidence: PCS. Frequency: 2/2. (PMID:21844578;PMID:33708531)
- Abnormal helix morphology (HP:0011039): An abnormality of the helix. The helix is the outer rim of the ear that extends from the insertion of the ear on the scalp (root) to the termination of the cartilage at the earlobe. Evidence: IEA. (OMIM:214100)
- 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: TAS. (OMIM:214100)
- Ulnar deviation of the hand or of fingers of the hand (HP:0001193). Evidence: IEA. (OMIM:214100)
- Flat face (HP:0012368): Absence of concavity or convexity of the face when viewed in profile. Evidence: TAS. (OMIM:214100)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- 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:214100)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:214100)
- 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: IEA. (OMIM:214100)
- Ulnar deviation of the hand (HP:0009487): Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger). Evidence: TAS. (OMIM:214100)
- Hypoplastic olfactory lobes (HP:0006894). Evidence: IEA. (OMIM:214100)
- Unsteady gait (HP:0002317). Evidence: PCS. Frequency: 1/2. (PMID:34513757)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: IEA. (OMIM:214100)
- 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:214100)
- Renal cortical microcysts (HP:0004734): Cysts of microscopic size confined to the cortex of the kidney. Evidence: IEA. (OMIM:214100)
- Brushfield spots (HP:0001088): The presence of whitish spots in a ring-like arrangement at the periphery of the iris. Evidence: IEA. (OMIM:214100)
- 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: 1/1. (PMID:21844578)
- 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: IEA. (OMIM:214100)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 1/2. (PMID:34513757)
- Clitoral hypertrophy (HP:0008665): Hypertrophy of the clitoris. Evidence: IEA. (OMIM:214100)
- Cubitus valgus (HP:0002967): Abnormal positioning in which the elbows are turned out. Evidence: IEA. (OMIM:214100)
- 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: IEA. (OMIM:214100)
- 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: 1/1. (PMID:33708531)
- 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:214100)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 1/1. (PMID:21844578)
These phenotypes are associated with the disease peroxisome biogenesis disorder 1A (Zellweger) (OMIM:214100).