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.

Microcephaly is a type of cephalic disorder. It has been classified in two types based on the onset:

Macrocephaly is customarily diagnosed if head circumference is greater than two standard deviations (SDs) above the mean. Relative macrocephaly occurs if the measure is less than two SDs above the mean, but is disproportionately above that when ethnicity and stature are considered. In research, cranial height or brain imaging is also used to determine intracranial volume more accurately.

Macrocephaly may be pathological, but many people with abnormally large heads or large skulls are healthy. Pathologic macrocephaly may be due to megalencephaly (enlarged brain), hydrocephalus (water on the brain), cranial hyperostosis (bone overgrowth), and other conditions. Pathologic macrocephaly is called "syndromic" when it is associated with any other noteworthy condition, and "nonsyndromic" otherwise. Pathologic macrocephaly can be caused by congenital anatomic abnormalities, genetic conditions, or by environmental events.

Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene, autism, "PTEN" mutations such as Cowden disease, neurofibromatosis type 1, and tuberous sclerosis; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome, Simpson-Golabi-Behmel syndrome (bulldog syndrome), and macrocephaly-capillary malformation (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome, Gorlin Syndrome, (also known as Basal Cell Nevus Syndrome) and cardiofaciocutaneous syndrome; Fragile X syndrome; leukodystrophies (brain white matter degeneration) such as Alexander disease, Canavan disease, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.

At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to schizophrenia and microcephaly.

Environmental events associated with macrocephaly include infection, neonatal intraventricular hemorrhage (bleeding within the infant brain), subdural hematoma (bleeding beneath the outer lining of the brain), subdural effusion (collection of fluid beneath the outer lining of the brain), and arachnoid cysts (cysts on the brain surface).

Megalencephaly-capillary (MCAP) is one of the two major syndromes of megalencephaly. Typically, MCAP and MPPH can be distinguished by somatic features. MCAP includes many characteristics that are observed at birth including: cutaneous vascular malformations, especially capillary malformations of the face and cutis marmorata, polydactyly, connective tissue dysplasia, and focal or segmental body overgrowth. Furthermore, MCAP can occasionally be linked with asymmetric brain overgrowth (hemimegalencephaly) as well as segmental overgrowth of the body (hemihypertrophy).

Hemimegalencephaly is an extremely rare form of macrocephaly and is characterized by uneven development of brain hemispheres (one-half of brain is larger than other). The syndrome can be presented by itself or in association with phakomatosis or hemigigantism. Additionally, hemimegalencephaly will frequently cause severe epilepsy, focal neuro-logical deficits, macrocrania, and mild to severe mental retardation.

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.

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.

Children with Weaver syndrome tend to look similar and have distinctive physical and craniofacial characteristics, which may include several, but not all of the following features:

- Macrocephaly

- Large bifrontal diameter

- Flattened occiput

- Long philtrum

- Retrognathia

- Round face in infancy

- Prominent chin crease

- Large ears

- Strabismus

- Hypertelorism

- Epicanthal folds

- Downslanting palpebral fissures

Other features may include loose skin, thin deep-set nails, thin hair, short ribs, limited elbow and knee extension, camptodactyly, and a coarse, low-pitched voice. Delayed development of motor skills such as sitting, standing, and walking are commonly exhibited in early childhood. Patients with Weaver syndrome typically have mild intellectual disability with poor coordination and balance. They also have some neurological abnormalities such as speech delay, epilepsy, intellectual disability, hypotonia or hypertonia, and behavioral problems.

Minor physical anomalies (MPAs) are relatively minor (typically painless and, in themselves, harmless) congenital physical abnormalities consisting of features such as low-set ears, single transverse palmar crease, telecanthus, micrognathism, macrocephaly, hypotonia and furrowed tongue. While MPAs may have a genetic basis, they might also be caused by factors in the fetal environment: anoxia, bleeding, or infection. MPAs have been linked to disorders of pregnancy and are thought by some to be a marker for insults to the fetal neural development towards the end of the first trimester. Thus, in the neurodevelopmental literature, they are seen as indirect indications of inferferences with brain development.

MPAs have been studied in autism, Down syndrome, and in schizophrenia. A 2008 meta-analysis found that MPAs are significantly increased in the autistic population. A 1998 study found that 60% of its schizophrenic sample and 38% of their siblings had 6 or more MPAs (especially in the craniofacial area), while only 5% of the control group showed that many.

The most often cited MPA, high arched palate, is described in articles as a microform of a cleft palate. Cleft palates are partly attributable to hypoxia. The vaulted palate caused by nasal obstruction and consequent mouth breathing, without the lateralising effect of the tongue, can produce hypoxia at night.

Other MPAs are reported only sporadically. Capillary malformation is induced by RASA1 mutation and can be changed by hypoxia. A study in the American Journal of Psychiatry by Trixler et al.: found hemangiomas to be highly significant in schizophrenia. Exotropia is reported as having low correlation and high significance as well. It can be caused by perinatal hypoxia.

Perlman syndrome shares clinical overlaps with other overgrowth disorders, with similarities to Beckwith–Wiedemann syndrome and Simpson-Golabi-Behmel syndrome having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial dysmorphology of Perlman, including deep-set eyes, depressed nasal bridge, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlaps with other disorders associated with Wilms tumor, namely, Sotos syndrome and Weaver syndrome.

This syndrome is characterized by overgrowth and advanced bone age. Affected individuals are dysmorphic, with macrodolichocephaly, downslanting palpebral fissures and a pointed chin. The facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers, and have an unusually large skull and large head. Adult height is usually in the normal range, although Broc Brown has the condition and was named the world's tallest teenager. As of late 2016, he was 7'8" and still growing.

Individuals with Sotos syndrome often have intellectual impairment, and most also have behavioral problems. Frequent behavioral impairments include attention deficit hyperactivity disorder (ADHD), phobias, obsessive compulsive disorder, tantrums, and impulsive behaviors (impulse control disorder). Problems with speech and language are also common. Affected individuals may often have stuttering, difficulty with sound production, or a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.

Other signs include scoliosis, seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience jaundice and poor feeding. A small number of patients with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If persons with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population.

Perlman syndrome (PS) (also called renal hamartomas, nephroblastomatosis and fetal gigantism) is a rare overgrowth disorder present at birth. It is characterized by polyhydramnios and fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor at an early age. The prognosis for Perlman syndrome is poor and it is associated with a high neonatal mortality.

Sotos syndrome (cerebral gigantism or Sotos-Dodge syndrome) is a rare genetic disorder characterized by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The disorder may be accompanied by autism, mild intellectual disability, delayed motor, cognitive, and social development, hypotonia (low muscle tone), and speech impairments. Children with Sotos syndrome tend to be large at birth and are often taller, heavier, and have relatively large skulls (macrocephaly) than is normal for their age. Signs of the disorder, which vary among individuals, include a disproportionately large skull with a slightly protrusive forehead, large hands and feet, large mandible, hypertelorism (an abnormally increased distance between the eyes)(large inter-pupillary distance), and downslanting eyes. Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur. Although most cases of Sotos syndrome occur sporadically, familial cases have also been reported. It is similar to Weaver syndrome.

Weaver syndrome (also called Weaver-Smith syndrome) is an extremely rare congenital disorder associated with rapid growth beginning in the prenatal period and continuing through the toddler and youth years. It is characterized by advanced osseous maturation, and distinctive craniofacial, skeletal, and neurological abnormalities. It was first described by Dr. David Weaver in 1974. It is similar to Sotos syndrome.

Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux).

The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, mental retardation, and developmental delay.

Overgrowth syndromes in children constitute a group of rare disorders that are typical of tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the genetic bases of these syndromes are unfolding. Any of the three embryonic tissue layers may be involved.The syndromes may manifest in localized or generalized tissue overgrowth. Latitudinal and longitudinal growth may be affected. Nevertheless, the musculoskeletal features are central to the diagnosis of some syndromes such as Proteus syndrome. The time of presentation of children with overgrowth syndromes is an important contributor to the differential diagnosis. Children with some overgrowth syndromes such as Klippel-Trenaunay-Weber syndrome can be readily detectable at birth. In contrast other overgrowth syndromes such as Proteus syndrome usually present in the postnatal period characteristically between the 2nd and 3rd year of life. In general, children with overgrowth syndromes are at increased risk of embryonic tumor development.

Examples of overgrowth syndromes include; Beckwith-Wiedemann syndrome, Proteus syndrome, Sotos syndrome, neurofibromatosis, Simpson-Golabi-Behmel syndrome, Weaver syndrome, Sturge–Weber syndrome, Macrocephaly-capillary malformation, CLOVES syndrome, fragile X syndrome and Klippel-Trenaunay-Weber syndrome.

Zori–Stalker–Williams syndrome, also known as pectus excavatum, macrocephaly, short stature and dysplastic nails, is a rare autosomal dominant congenital disorder associated with a range of features such as pectus excavatum, macrocephaly and dysplastic nails, familial short stature, developmental delay and distinctive facies. Further signs are known to be associated with this syndrome.

The name originates from the researchers who first defined and noticed the syndrome and its clinical signs.

It is believed that the syndrome is inherited in an autosomal dominant pattern, though there has been no new research undertaken for this rare disease.

Individuals affected by ischiopatellar dysplasia commonly have abnormalities of the patella and pelvic girdle, such as absent or delayed patellar and ischial ossification as well as infra-acetabular axe-cut notches. Patellae are typically absent or small in these individuals, when patellae are present they are small and laterally displaced or dislocated. In addition, abnormalities in other parts of their skeleton and dysmorphic features are common in those affected. Other features that have been identified in patients with ischiopatellar dysplasia include foot anomalies, specifically flat feet (pes planus), syndactylism of the toes, short fourth and fifth toes, and a large gap between the first and second toes, femur anomalies, cleft palate, and craniofacial dysmorphisms.

Along with the four aspects of the disorder that give it its name, there are also other common symptoms:

- A downward slant of the forehead

- Delayed bone maturation

- Mental retardation

The ocular abnormalities are generally retinal coloboma and nystagmus.

Nearly all individuals show multiple café au lait spots.Features common in neurofibromatosis - Lisch nodules, bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors - are absent in this condition Symptoms however, may include:

- Freckles

- Lipomas

- Macrocephaly

- Learning disabilities

- ADHD

- Developmental delay

Cardiofaciocutaneous Syndrome (CFC syndrome) is an extremely rare and serious genetic disorder.

It is characterized by the following:

- Distinctive facial appearance

- Unusually sparse, brittle, curly scalp hair

- A range of skin abnormalities from dermatitis to thick, scaly skin over the entire body (generalized ichthyosis)

- Heart malformations (congenital or appearing later) especially an obstruction of the normal flow of blood from the lower right ventricle of the heart to the lungs (valvar pulmonary stenosis)

- Delayed growth

- Foot abnormalities (extra toe or fusion of two or more toes)

Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign mesodermal hamartomas (multiple hemangiomas, and intestinal polyps). Dysmorphy as well as delayed neuropsychomotor development can also be present. The head enlargement does not cause widening of the ventricles or raised intracranial pressure; these individuals have a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue.

Some individuals have thyroid issues consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer,

most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression

Diagnosis is visual with measurement of spot size. The number of spots can have clinical significance for diagnosis of associated disorders such as Neurofibromatosis type I. Greater than or equal to 6 spots of at least 5mm in diameter in pre-pubertal children and at least 15mm in post-pubertal individuals is one of the major diagnostic criteria for NF1.

FG syndrome's major clinical features include intellectual disability, usually severe; hyperactive behavior, often with an outgoing personality; severe constipation, with or without structural anomalies in the anus such as imperforate anus; macrocephaly; severe hypotonia; a characteristic facial appearance due to hypotonia, giving a droopy, "open-mouthed" expression, a thin upper lip, a full or pouting lower lip, and partial or complete loss of the corpus callosum. About a third of reported cases of individuals with FG syndrome die in infancy, usually due to respiratory infection; premature death is rare after infancy.