Neurocutaneous melanosis is associated with the presence of either giant congenital melanocytic nevi or non-giant nevi of the skin. It is estimated that neurocutaneous melanosis is present in 2% to 45% of patients with giant congenital melanocytic nevi. Patients with non-giant congenital melanocytic nevi seem to have a much lower, but undefined risk. Of these patients, only a small number are symptomatic, usually displaying symptoms before the age of 2.

These symptoms are the result of melanocytic lesions being present in the leptomeninges of the central nervous system.

Symptoms can include:

- Papilledema

- Cranial palsies

- Headache

- Vomiting

- Seizures

Others symptoms may also exist that are related to an increase in intracranial pressure. These symptoms seem to be present regardless of the malignancy of the melanin deposits within the central nervous system.

Approximately 10% of patient with neurocutaneous melanosis also present the Dandy–Walker syndrome and associated Dandy-Walker malformation. This malformation involves an enlargement of the posterior fossae and fourth ventricle along with agenesis of the cerebellar vermis. The abnormalities of the leptomeninges during fetal development due to neurocutaneous melanosis may be the cause of this increased incidence of the Dandy-Walker malformation. The development of hydrocephalus is the most common symptom associated with a combination of neurocutaneous melanosis and a Dandy-Walker malformation, occurring in about two out of three patients.

Symptoms vary according to the abnormality, but often feature poor muscle tone and motor function, seizures, developmental delays, mental retardation, failure to grow and thrive, difficulties with feeding, swelling in the extremities, and a smaller than normal head. Most infants with an NMD appear normal, but some disorders have characteristic facial or skull features that can be recognized by a neurologist.

Microlissencephaly Type B or Barth microlissencephaly syndrome: is a microlissencephaly with thick cortex, severe cerebellar and brainstem hypoplasia. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes.

This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), severe congenital microcephaly, weak respiratory effort, and survival for only a few hours or days. Barth described two siblings with this type as having a very low brainweight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.

Microlissencephaly with mildly to moderately thick (6–8 mm) cortex, callosal agenesis

The DWS malformation is the most severe presentation of the syndrome. The posterior fossa is enlarged and the tentorium is in high position. There is complete agenesis of the cerebellar vermis. There is also cystic dilation of the fourth ventricle, which fills the posterior fossa. This often involves hydrocephalus and complications due to associated genetic conditions, such as Spina Bifida.

The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. An increase in the size of the fluid spaces surrounding the brain as well as an increase in pressure may also be present. The syndrome can appear dramatically or develop unnoticed.

Symptoms, which often occur in early infancy, include slower motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure such as irritability, vomiting, and convulsions and signs of cerebellar dysfunction such as unsteadiness and lack of muscle coordination or jerky movements of the eyes may occur. Other symptoms include increased head circumference, bulging at the back of the skull, problems with the nerves that control the eyes, face and neck, and abnormal breathing patterns.

Dandy–Walker syndrome is frequently associated with disorders of other areas of the central nervous system including absence of the corpus callosum, the bundle of axons connecting the two cerebral hemispheres, and malformations of the heart, face, limbs, fingers and toes.

The Dandy–Walker complex is a genetically sporadic disorder that occurs one in every 30,000 live births. Prenatal diagnosis and prognosis of outcomes associated with Dandy–Walker can be difficult. Prenatal diagnosis is possible with ultrasound. Because the syndrome is associated with an increased risk for fetal karyotype abnormalities, amniocentesis can be offered after prenatal diagnosis. There is a relative contraindication of taking Warfarin during pregnancy, as it is associated with an increased risk of Dandy–Walker syndrome if taken during the first trimester.

The prognosis for children with NMDs varies depending on the specific disorder and the degree of brain abnormality and subsequent neurological signs and symptoms.

Schizencephaly can be distinguished from porencephaly by the fact that in schizencephaly the fluid-filled component, if present, is entirely lined by heterotopic grey matter while a porencephalic cyst is lined mostly by white matter. Individuals with clefts in both hemispheres, or bilateral clefts, are often developmentally delayed and have delayed speech and language skills and corticospinal dysfunction. Individuals with smaller, unilateral clefts (clefts in one hemisphere) may be weak or paralyzed on one side of the body and may have average or near-average intelligence. Patients with schizencephaly may also have varying degrees of microcephaly, Intellectual disability, hemiparesis (weakness or paralysis affecting one side of the body), or quadriparesis (weakness or paralysis affecting all four extremities), and may have reduced muscle tone (hypotonia). Most patients have seizures, and some may have hydrocephalus.

Phenotypic expression varies greatly between individuals with CFND. Some of the more prominent characteristics are:

- Craniosynostosis of the coronal suture(s) (fusion of the coronal sutures),

- Orbital hypertelorism (increased interocular distance),

- Bifid nasal tip,

- Dry frizzy curled hair,

- Longitudinal ridging and / or splitting of the nails,

- Facial Asymmetry.

Other characteristics that are less frequently seen are: broad nasal base, low anterior hair line, low set ears, crowding of the teeth, maxillary hypoplasia, rounded and sloping shoulders, pectus excavatum, scoliosis, high arched palate, orbital dystopia, low implant of the breasts with asymmetric nipples and volume, webbed neck, hand or foot abnormalities such as clinodactyly (most common is a curved 5th finger) and cutaneous syndactyly (webbed fingers / toes).

Females are more commonly and usually more severely affected than males. Males can however have (some of) the same symptoms as females, but this is not frequently seen. Most males have mild symptoms such as hypertelorism and a broad nasal base with bifid nose, but can also be a carrier of the mutation yet stay clinically unaffected.

BFPP is a cobblestone-like cortical malformation of the brain. Disruptions of cerebral cortical development due to abnormal neuronal migration and positioning usually lead to cortical disorders, which includes cobblestone lissencephaly. Cobblestone lissencephaly is typically seen in three different human congenital muscular dystrophy syndromes: Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease. In cobblestone lissencephaly, the brain surface actually has a bumpy contour caused by the presence of collections of misplaced neurons and glial cells that have migrated beyond the normal surface boundaries of the brain. Sometimes regions populated by these misplaced cells have caused a radiologic misdiagnosis of polymicrogyria. However, the presence of other abnormalities in these cobblestone lissencephaly syndromes, including ocular anomalies, congenital muscular dystrophy, ventriculomegaly, and cerebellar dysplasia, usually distinguishes these disorders from polymicrogyria. There are no anatomopathologic studies that have characterized the pattern of cortical laminar alterations in patients with GPR56 gene mutations, but it has been suggested that the imaging characteristics of BFPP, including myelination defects and cerebellar cortical dysplasia, are reminiscent of those of the so-called cobblestone malformations (muscle-eye-brain disease and Fukuyama congenital muscular dystrophy) that are also associated with N-glycosylation defects in the developing brain.

Lissencephaly ("smooth brain") is the extreme form of pachygyria. In lissencephaly, few or no sulci are seen on the cortical surface, resulting in a broad, smooth appearance to the entire brain. Lissencephaly can be radiologically confused with polymicrogyria, particularly with low-resolution imaging, but the smoothness and lack of irregularity in the gray-white junction, along with markedly increased cortical thickness, distinguishes lissencephaly.

GPR56 mutation also can cause a severe encelphalopathy which is associated with electro clinical features of the Lennox-Gastaut syndrome. Lennox-Gastaut syndrome can be cryptogenic or symptomatic, but the symptomatic forms have been associated with multiple etiologies and abnormal cortical development. BFPP caused by GPR56 mutations is a representation of a malformation of cortical development that causes Lennox-Gastaut Syndrome.

Polymicrogyria usually gets misdiagnose with pacygyria so therefore it needs to be distinguished from pachygyria. Pachygyria is a distinct brain malformation in which the surface folds are excessively broad and sparse. Pachygyria and polymicrogyria may look similar on low-resolution neuroimaging such as CT because the cortical thickness can appear to be increased and the gyri can appear to be broad and smooth in both conditions. This is why higher resolution neuroimaging are needed such as an MRI.

Neurocutaneous melanosis is a congenital disorder characterized by the presence of congenital melanocytic nevi on the skin and melanocytic tumors in the leptomeninges of the central nervous system. These lesions may occur in the amygdala, cerebellum, cerebrum, pons, and spinal cord of patients. Although typically asymptomatic, malignancy occurs in the form of leptomeningeal melanoma in over half of patients. Regardless of the presence of malignancy, patients with symptomatic neurocutaneous melanosis generally have a poor prognosis with few treatment options. The pathogenesis of neurocutaneous melanosis is believed to be related to the abnormal postzygotic development of melanoblasts and mutations of the NRAS gene.

Diagnosis is usually based on clinical observation. Various sets of criteria have been suggested to identify the disorder in an individual patient, all of which include macrocephaly and a number of the following: somatic overgrowth, cutis marmorata, midline facial birthmark, polydactyly/syndactyly, asymmetry (hemihyperplasia or hemihypertrophy), hypotonia at birth, developmental delay, connective tissue defect and frontal bossing. Currently no consensus exists about which diagnostic criteria are definitive and so evaluation by a medical geneticist or other clinician with familiarity with the syndrome is usually needed to provide diagnostic certainty. It is not clear if there are some features which are mandatory to make the diagnosis, but macrocephaly appears essentially universal though may not be congenital. The distinctive vascular abnormalities of the skin often fade over time, making the diagnosis challenging in older children with this condition.

The brain can be affected in several ways in this syndrome. Some children are born with structural brain anomalies such as cortical dysplasia or polymicrogyria. While developmental delay is nearly universal in this syndrome it is variable in severity, with the majority having mild to moderate delays and a minority having severe cognitive impairment. Some patients are affected with a seizure disorder. White matter abnormalities on magnetic resonance imaging (MRI), suggesting a delay in white matter myelination, is commonly seen in early childhood. Some patients may have asymmetry of the brain, with one side being noticeably larger than the other.

One interesting phenomenon that seems very common in this syndrome is the tendency for disproportionate brain growth in the first few years of life, with crossing of percentiles on the head circumference growth charts. A consequence of this disproportionate brain growth appears to be a significantly increased risk of cerebellar tonsillar herniation (descent of the cerebellar tonsils through the foramen magnum of the skull, resembling a Chiari I malformation neuroradiologically) and ventriculomegaly/hydrocephalus. Such cerebellar tonsil herniation may occur in up to 70% of children with M-CM.

The medical literature suggests that there is a risk of cardiac arrhythmias in early childhood. The cause for this is unknown. In addition, a variety of different congenital cardiac malformations have been reported in a small number of patients with this disorder.

Like other syndromes associated with disproportionate growth, there appears to be a slightly increased risk of certain types of childhood malignancies in M-CM (such as Wilms' tumor). However, the precise incidence of these malignancies is unclear.

Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.

Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria). The types of seizures associated with lissencephaly include:

- persisting spasms

- focal seizures

- tonic seizures

- atypical seizures

- atonic seizures

Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes. Over 90% of children affected with lissencephaly have seizures.

Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.

Craniofrontonasal dysplasia (craniofrontonasal syndrome, craniofrontonasal dysostosis, CFND) is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1). Phenotypic expression varies greatly amongst affected individuals, where females are more commonly and generally more severely affected than males.

Common physical malformations are: craniosynostosis of the coronal suture(s), orbital hypertelorism, nasal tip, dry frizzy curled hair, longitudinal ridging and/or splitting of the nails, and facial asymmetry.

The diagnosis CFND is determined by the presence of a mutation in the EFNB1 gene. Physical characteristics may play a supportive role in establishing the diagnosis.

The treatment is always surgical and is based on each patients specific phenotypic presentation.

Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and cutaneous, vascular, neurologic, and limb abnormalities. Though not every patient has all features, commonly found signs include macrocephaly, congenital macrosomia, extensive cutaneous capillary malformation (naevus flammeus or port-wine stain type birthmark over much of the body; a capillary malformation of the upper lip or philtrum is seen in many patients with this condition), body asymmetry (also called hemihyperplasia or hemihypertrophy), polydactyly or syndactyly of the hands and feet, lax joints, doughy skin, variable developmental delay and other neurologic problems such as seizures and low muscle tone.

Classification systems for malformations of the cerebellum are varied and are constantly being revised as greater understanding of the underlying genetics and embryology of the disorders is uncovered. A classification proposed by Patel S in 2002 divides cerebellar malformations in two broad groups; those with cerebellar hypoplasia and; those with cerebellar dysplasia.

- I. Cerebellar hypoplasia

- A. Focal hypoplasia

- 1. Isolated vermis

- 2. One hemisphere hypoplasia

- B. Generalized hypoplasia

- 1. With enlarged fourth ventricle (“cyst,”), Dandy-Walker continuum

- 2. Normal fourth ventricle (no “cyst”)

- a. With normal pons

- b. With small pons i. Normal foliation

- a) Pontocerebellar hypoplasias of Barth, types I and II

- b) Cerebellar hypoplasias, not otherwise specified

There are different tests or methods used to determine GPR56 expression or visuals of the brain to analyze the specific sections that are affected. These tests for example, using animals such as mice, RNAi, Behavioral assay, Electron microscopy, CT scan, or MRI demonstrate different results that concludes an affected BFPP patient. MRI's reveal either irregularity to the cortical surface suggestive of multiple small folds or an irregular, scalloped appearance of the gray matter-white matter junction.

Neuroimaging The diagnosis of polymicrogyria is typically made by magnetic resonance imaging (MRI) since computed tomography (CT) and other imaging methods generally do not have high enough resolution or adequate contrast to identify the small folds that define the condition. The cerebral cortex often appears abnormally thick as well because the multiple small gyri are fused, infolded, and superimposed in appearance.

Neuropathology Gross neuropathologic examination reveals a pattern of complex convolutions to the cerebral cortex, with miniature gyri fused and superimposed together, often resulting in an irregular brain surface. The cortical ribbon can appear excessively thick as a result of the infolding and fusion of multiple small gyri.

Microscopic examination demonstrates that the cerebral cortex is in fact abnormally thin and has abnormal lamination; typically the cortex is unlayered or has four layers, in contrast to the normal six layers. The most superficial layers between adjacent small gyri appear fused, with the pia (layer of the meninges) bridging across multiple gyri. Prenatal diagnosis for BFPP is also available for pregnancies at risk if the GPR56 mutations have been identified in an affected family member.

Non-progressive early onset ataxia and poor motor learning are the commonest presentation.

Affected children display severe psychomotor retardation, failure to thrive, seizures, and muscle spasticity or hypotonia. Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, fingers, or toes.

Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is an autosomal multisystem disorder including severe pre- and post-natal growth retardation, microcephaly with Seckel syndrome-like facial appearance, and distinctive skeletal alterations. Usually those affected have mild to moderate mental retardation. This female child is the first born of nonconsanguineous parents at 35 weeks gestation through a cesarean section due to intrauterine growth retardation. She had a retarded psychomotor development and was repeatedly hospitalized during her first six months of life due to recurring respiratory infections. Her electroencephalography, auditory brainstem response evaluation, and chromosomal analysis were relatively normal. A brain MRI revealed thickened cerebral cortices with few and large gyri prominently in the frontal and posterior temporal regions, incomplete development of the Sylvian fissures, and dilatation of the posterior horns of the lateral ventricles (colpocephaly). Usually only mild brain malformations are associated with MOPD type II. The imaging findings of this child’s brain most likely represent diffuse pachygyria, a mild form of lissencephaly. This child’s neurodevelopmental findings were mild when compared to previous reports of a well-defined chromosome 17-linked and X-linked lissencephaly in a bedridden patient with severe developmental delays.

Callosal disorders can be diagnosed through brain imaging studies or during autopsy. They may be diagnosed through an MRI, CT scan, Sonography, prenatal ultrasound, or prenatal MRI.

The blockage of cerebrospinal fluid (CSF) flow may also cause a syrinx to form, eventually leading to syringomyelia. Central cord symptoms such as hand weakness, dissociated sensory loss, and, in severe cases, paralysis may occur.

Some syndromes that frequently include ACC are Aicardi syndrome, Andermann syndrome, Shapiro syndrome, acrocallosal syndrome, septo-optic dysplasia (optic nerve hypoplasia), Mowat–Wilson syndrome, John Sayden syndrome, Menkes syndrome, and L1CAM Syndrome. Some conditions that are sometimes associated with ACC include maternal nutritional deficiencies or infections, metabolic disorders, fetal alcohol syndrome, craniofacial abnormalities, and other oral and maxillofacial pathologies.

Affected newborns generally have striking neurological defects and seizures. Severely impaired development is common, but disturbances in motor functions may not appear until later in life.

Infants with microcephaly are born with either a normal or reduced head size. Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled scalp. As the child grows older, the smallness of the skull becomes more obvious, although the entire body also is often underweight and dwarfed. Development of motor functions and speech may be delayed. Hyperactivity and intellectual disability are common occurrences, although the degree of each varies. Convulsions may also occur. Motor ability varies, ranging from in some to spastic quadriplegia in others.

Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic neural crest cell lineage. The term was coined by Robert P. Bolande in 1974.

Accepted examples are piebaldism, Waardenburg syndrome, Hirschsprung disease, Ondine's curse (congenital central hypoventilation syndrome), pheochromocytoma, paraganglioma, Merkel cell carcinoma, multiple endocrine neoplasia, neurofibromatosis type I, CHARGE syndrome, familial dysautonomia, DiGeorge syndrome, Axenfeld-Rieger syndrome, Goldenhar syndrome (a.k.a. hemifacial microsomia), craniofrontonasal syndrome, congenital melanocytic nevus, melanoma, and certain congenital heart defects of the outflow tract, in particular.

Multiple sclerosis has also been suggested as being neurocristopathic in origin.

The usefulness of the definition resides in its ability to refer to a potentially common etiological factor for certain neoplasms and/or congenital malformation associations that are otherwise difficult to group with other means of nosology.