- 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: 52/77. (PMID:16278854)
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 2/2. (PMID:9345094)
- 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: PCS. Frequency: 40/73. (PMID:16278854)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 29/64. (PMID:16278854)
- Thoracic hypoplasia (HP:0005257). Evidence: IEA. (OMIM:261515)
- 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: 79/85. Onset: Neonatal onset (HP:0003623). (PMID:16278854)
- Decreased muscle mass (HP:0003199). Evidence: IEA. (OMIM:261515)
- 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:9345094)
- Split hand (HP:0001171): A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands. Evidence: IEA. (OMIM:261515)
- Increased circulating very long-chain fatty acid concentration (HP:0033643): Increased concentration of very long-chain fatty acids in the blood circulation. Very long-chain fatty acids are fatty acids (FAs) with a chain-length of 22 or more carbons. Evidence: PCS. Frequency: 1/1. (PMID:9345094)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 40/73. (PMID:16278854)
- Bile duct proliferation (HP:0001408): Proliferative changes of the bile ducts. Evidence: PCS. Frequency: 2/23. (PMID:16278854)
- Cortical dysplasia (HP:0002539): The presence of developmental dysplasia of the cerebral cortex. Evidence: IEA. (OMIM:261515)
- 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: 52/77. (PMID:16278854)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Onset: Neonatal onset (HP:0003623). (PMID:16278854)
- Cerebral hypoplasia (HP:0006872): Underdevelopment of the cerebrum. Evidence: PCS. Frequency: 5/11. (PMID:16278854)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 52/77. (PMID:16278854)
- Hammertoe (HP:0001765): Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint. Evidence: IEA. (OMIM:261515)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/2. (PMID:9345094)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: PCS. Frequency: 21/61. (PMID:16278854)
- 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:261515)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 6/11. (PMID:16278854)
- 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: 126/126. (PMID:16278854)
- Very long chain fatty acid accumulation (HP:0008167). Evidence: PCS. Frequency: 2/2. (PMID:9345094)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- 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:16278854)
- Decreased nerve conduction velocity (HP:0000762): A reduction in the speed at which electrical signals propagate along the axon of a neuron. Evidence: PCS. Frequency: 16/24. (PMID:16278854)
- 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: 52/77. (PMID:16278854)
- Primary adrenal insufficiency (HP:0008207): Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands as a result of a primary defect in the glands themselves. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: IEA. Frequency: 5/23. (PMID:16278854)
- Scaphocephaly (HP:0030799): Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis. Evidence: PCS. Frequency: 11/12. (OMIM:261515;PMID:9345094)
- Cholestasis (HP:0001396): Impairment of bile flow due to obstruction in bile ducts. Evidence: PCS. Frequency: 2/23. (PMID:16278854)
- 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: PCS. Frequency: 1/2. (PMID:9345094)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 52/77. (PMID:16278854)
- 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: 8/49. (PMID:16278854)
- Fetal ascites (HP:0001791): Accumulation of fluid in the peritoneal cavity during the fetal period. Evidence: IEA. (OMIM:261515)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 32/73. (PMID:16278854)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 27/61. (PMID:16278854)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: IEA. (OMIM:261515)
- Cerebral dysmyelination (HP:0007266): Defective structure and function of myelin sheaths of the white matter of the brain. Evidence: PCS. Frequency: 4/11. (PMID:16278854)
- 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: IEA. (OMIM:261515)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 16/53. (PMID:16278854)
- 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: PCS. Frequency: 1/2. (PMID:9345094)
- Calcific stippling (HP:0002832): An abnormal punctate (speckled, dot-like) pattern of calcifications in soft tissues within or surrounding bones (as observed on radiographs). Evidence: PCS. Frequency: 12/12. (PMID:16278854;PMID:9345094)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 2/2. (PMID:9345094)
- 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: PCS. Frequency: 52/77. (PMID:16278854)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 4/67. (PMID:16278854)
- Undetectable electroretinogram (HP:0000550): Lack of any response to stimulation upon electroretinography. Evidence: PCS. Frequency: 17/22. (PMID:16278854)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: IEA. (OMIM:261515)
- 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: 1/2. (PMID:9345094)
- Delayed cranial suture closure (HP:0000270): Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: IEA. (OMIM:261515)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- Corpus callosum atrophy (HP:0007371): The presence of atrophy (wasting) of the corpus callosum. Evidence: PCS. (PMID:16278854)
- Motor regression (HP:0033044): Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones. Evidence: PCS. Frequency: 7/61. (PMID:16278854)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: PCS. Frequency: 4/12. (PMID:16278854)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 52/77. (PMID:16278854)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: PCS. Frequency: 83/85. Onset: Neonatal onset (HP:0003623). (PMID:16278854)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: IEA. (OMIM:261515)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/2. (PMID:9345094)
- 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: 7/11. (PMID:16278854)
These phenotypes are associated with the disease d-bifunctional protein deficiency (OMIM:261515).