Phenotypes associated with the disease neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language (OMIM:621150):
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: PCS. Frequency: 2/2. (PMID:30787422)
- 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: 1/1. (PMID:36576126)
- Recurrent aspiration pneumonia (HP:0002100): Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia. Evidence: PCS. Frequency: 1/5. (PMID:38083972;PMID:36576126)
- 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: 0/1. (PMID:38083972)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 3/4. (PMID:38083972;PMID:36576126)
- 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: 0/4. (PMID:38083972;PMID:36576126)
- 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: 1/4. (PMID:36576126)
- 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: 3/3. (PMID:30787422)
- 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: 2/4. (PMID:36576126)
- Appendicular hypotonia (HP:0012389): Muscular hypotonia of one or more limbs. Evidence: PCS. Frequency: 1/1. (PMID:38083972)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 3/3. (PMID:30787422;PMID:38083972)
- 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: PCS. Frequency: 4/4. (PMID:36576126)
- Developmental stagnation (HP:0007281): A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills. Evidence: PCS. Frequency: 1/1. (PMID:36576126)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 4/5. (PMID:38083972;PMID:36576126)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:38083972)
- Arachnoid cyst (HP:0100702): An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid. Evidence: PCS. Frequency: 2/4. (PMID:36576126)
- 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: 3/4. (PMID:30787422;PMID:38083972)
- 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:38083972)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 2/2. (PMID:30787422)
- 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:30787422)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/4. (PMID:30787422;PMID:38083972)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 2/4. (PMID:36576126)
- 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: 1/1. (PMID:38083972)
- Interictal EEG abnormality (HP:0025373): Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge. Evidence: PCS. Frequency: 5/6. (PMID:30787422;PMID:36576126)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 7/7. (PMID:30787422;PMID:36576126)
- 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:38083972)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 3/3. (PMID:30787422)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 3/3. (PMID:30787422)
- Limb joint contracture (HP:0003121): A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 3/4. (PMID:36576126)
- 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: 1/1. (PMID:38083972)
- Tetraparesis (HP:0002273): Weakness of all four limbs. Evidence: PCS. Frequency: 4/4. (PMID:36576126)
- Severely reduced visual acuity (HP:0001141): Severe reduction of the ability to see. On the 6m visual acuity scale, severe reduction is defined as less than 6/60 but at least 3/60. On the 20ft visual acuity scale, severe reduction is defined as less than 20/200 but at least 20/400. On the decimal visual acuity scale, severe reduction is defined as less than 0.1 but at least 0.05. Evidence: PCS. Frequency: 1/1. (PMID:36576126)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 3/4. (PMID:36576126)
- Tube feeding (HP:0033454): Feeding problem necessitating food and nutrient delivery via a tube. Evidence: PCS. Frequency: 2/5. (PMID:38083972;PMID:36576126)
- Appendicular spasticity (HP:0034353): A type of spasticity that affects one or more limbs (arms or legs). Evidence: PCS. Frequency: 4/5. (PMID:38083972;PMID:36576126)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 1/4. (PMID:36576126)
- 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:28097321)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 2/3. (PMID:38083972;PMID:36576126)
- 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: 2/2. (PMID:36576126)
- 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: PCS. Frequency: 1/1. (PMID:38083972)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 3/4. (PMID:30787422;PMID:38083972)
- 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: 4/4. (PMID:36576126)