Microcephaly is a disorder in which the circumference of the head is smaller than average for the person's age and gender. Most children with microcephaly also have a smaller than typical brain and intellectual disability. Some of the most common signs and symptoms associated with microcephaly are seizures, poor feeding, high pitched cry, intellectual disability, developmental delay, and increased movement of arms and legs.

Vision abnormalities in children with 1p36 have been wide-ranging, including:

Recognised symptoms up till now are:

- Autism or autistic behaviors

- ADHD

- Learning disability

- Large head

- Dysmorphic facial appearance - mild

- Prominent forehead

- Wide-set eyes (hypertelorism)

- Schizophrenia

- Loose joints

- GERD

- Sleep disturbances

- Sleep Apnea

- Underdeveloped parts of brain - corpus callosum and cerebellar vermis

- Neuroblastoma

- Speech & developmental delays

- Chiari malformation of the brain

- Congenital heart defects

- Hypotonia

It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The symptomology may be different among individuals, even in the same family.

The brain is abnormally smooth, with fewer folds and grooves. The face, especially in children, has distinct characteristics including a short nose with upturned nares, thickened upper lip with a thin vermilion upper border, frontal bossing, small jaw, low-set posteriorily rotated ears, sunken appearance in the middle of the face, widely spaced eyes, and hypertelorism. The forehead is prominent with bitemporal hollowing.

Characteristics that are not visual include mental retardation, pre- and postnatal growth retardation, epilepsy, and reduced lifespan.

Failure to thrive, feeding difficulties, seizures and decreased spontaneous activity are often seen. Death usually occurs in infancy and childhood.

Multiple abnormalities of the brain, kidneys, and gastrointestinal tract (the stomach and intestines) may occur.

Physical Symptoms

- Heart Defects

- Characteristics of Autism

- Genital defects (in males)

- Childhood hypotonia

- Respiratory infections

- Motor Delay

- Renal defects

Behavioural Symptoms

- Passiveness

- Sociability

- Aggression

- Biting, and/or hitting

- Moodiness

- Disliking routine changes

Affected individuals present with a broad array of medical and behavioral manifestations (tables 1 and 2). Patients are consistently characterized by global developmental delay, intellectual disability, speech abnormalities, ASD-like behaviors, hypotonia and mild dysmorphic features. Table 1 summarizes the dysmorphic and medical conditions that have been reported in individuals with PMS. Table 2 summarize the psychiatric and neurological associated with PMS. Most of the studies include small samples or relied on parental report or medical record review to collect information, which can account in part for the variability in the presentation of some of the presenting features. Larger prospective studies are needed to further characterize the phenotype.

Table 1: Dysmorphic features and medical comorbid conditions that have been reported in individuals with Phelan McDermid Syndrome.

Table 2: Psychiatric and Neurologic Manifestations associated with Phelan McDermid Syndrome

The three most common symptoms of Opitz G/BBB syndrome (both type I & II) are hypertelorism (exceptionally wide-spaced eyes), laryngo-tracheo-esophalgeal defects (including clefts and holes in the palate, larynx, trachea and esophagus) and hypospadias (urinary openings in males not at the tip of the penis) (Meroni, Opitz G/BBB syndrome, 2012). Abnormalities in the larynx, trachea and esophagus can cause significant difficulty breathing and/or swallowing and can result in reoccurring pneumonia and life-threatening situations. Commonly, there may be a gap between the trachea and esophagus, referred to as a laryngeal cleft; which can allow food or fluid to enter the airway and make breathing and eating a difficult task.

Genital abnormalities like a urinary opening under the penis (hypospadias), undescended testes (cryptorchidism), underdeveloped scrotum and a scrotum divided into two lobes (bifid scrotum) can all be commonplace for males with the disease.

Developmental delays of the brain and nervous system are also common in both types I and II of the disease. 50% of people with Opitz G/BBB Syndrome will experience developmental delay and mild intellectual disability. This can impact motor skills, speech and learning capabilities. Some of these instances are likened to autistic spectrum disorders. Close to half of the people with Opitz G/BBB Syndrome also have a cleft lip (hole in the lip opening) and possibly a cleft palate (hole in the roof of the mouth), as well. Less than half of the people diagnosed have heart defects, imperforate anus (obstructed anal opening), and brain defects. Of all the impairments, female carriers of X-linked Type I Opitz G/BBB Syndrome usually only have ocular hypertelorism.

Cognitive ability in individuals with 18p- varies widely, with most falling in the mild to moderate range of impairment, though there have been some reports of people with impairment in the severe to profound range. These individuals may have had holoprosencephaly, which is frequently associated with severe impairment.

Speech deficits are quite common within this population. Frequently, expressive speech lags behind other developmental parameters.

Facial features of children with Smith–Magenis syndrome include a broad face, deep-set eyes, large cheeks, and a prominent jaw, as well as a flat nose bridge. The mouth curves downwards and the upper lip curves outwards. These facial features become more noticeable as the individual ages.

Disrupted sleep patterns are characteristic of Smith–Magenis syndrome, typically beginning early in life. Affected people may be very sleepy during the day, but have trouble falling asleep and awaken several times each night, due to an inverted circadian rhythm of melatonin.

People with Smith–Magenis syndrome have engaging personalities, but all also have a lot of behavioral problems. These behavioral problems include frequent temper tantrums, meltdowns and outbursts, aggression, anger, fidgeting, compulsive behavior, anxiety, impulsiveness, and difficulty paying attention. Self-harm, including biting, hitting, head banging, and skin picking, is very common. Repetitive self-hugging is a behavioral trait that may be unique to Smith–Magenis syndrome. People with this condition may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.

Other symptoms can include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia), strabismus, and other problems with vision. Heart and kidney defects also have been reported in people with Smith–Magenis syndrome, though they are less common.

Almost all children with Jacobsen syndrome have Intellectual disabilities, which ranges from mild to moderate depending upon the number of the deletion of genes from the chromosome. Children with intellectual disability take more time than normal to learn new things and acquire new skills. They have problems with assembling new information or adapting to novel situations and associating two events or things together.

Most kids with the syndrome have delayed development including delayed speech, motor disabilities, lack of coordination, which makes even simple activities like sitting, standing and walking difficult for these children. Most kids eventually start speaking but in cases with severe intellectual disability language use is highly restricted.

They have distinctive facial features like:

- Small head (microcephaly)

- Pointed forehead, (trigonocephaly)

- Small ears which are low-set

- Widely-spaced eyes (hypertelorism)

- Droopy eyelids (ptosis)

- Broad nasal bridge

- Abnormally thin upper lips

- Downturned corners of the mouth

- Excess skin covering in the inner corner of eyes (epicanthal folds)

Some children also suffer from behavioural problems like distractibility, hyperactivity, impaired communication and social skills which qualifies them for a diagnosis of ASD and ADHD.

Heart defects are very common in children with Jacobsen Syndrome. 88.5% of people with the disorder have Paris-Trousseau syndrome which is a bleeding disorder and causes a lifelong risk of abnormal bleeding and bruising due to dysfunction in the platelets.

Other symptoms may include eye problems, ear and sinus infections, hearing problems, bone deformities, growth hormone deficiency, gastrointestinal problems, kidney malfunctions etc.

The symptoms associated with this syndrome are variable, but common features include: low birthweight, low muscle tone at birth, poor feeding in infancy (often requiring feeding by tube for a period) and oromotor dyspraxia together with moderate developmental delays and learning disabilities but amiable behaviour. Other clinically important features include epilepsy, heart defects (atrial septal defect, ventricular septal defect) and kidney/urological anomalies. Silvery depigmentation of strands of hair have been noted in several patients. With age there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups, with each group reporting several patients, and is now recognised to be one of the more common recurrent microdeletion syndromes. Recently a patient with a small duplication in same segment of DNA has been described. An overview of the clinical features of the syndrome, by reviewing 22 individuals with a 17q21.31 microdeletion, estimated the disorder is present in one in every 16,000 people.

Almost all patients with this syndrome have some degree of mental retardation and facial dysmorphism (round face, deep-set eyes, thin upper lip). Behavioural problems are common. Brachymetaphalangism (metacarpal or metatarsal shortening) is reported in ~50% of cases overall, but is typically not evident below the age of 2 years. There is striking phenotypic variability, and the size and extent of the deleted region cannot be used as accurate predictors of prognosis. Some patients have additional problems such as congenital heart disease and seizures.

The features associated with this condition include: mild to moderate learning difficulties, short stature, unique facial features, small head and skeletal abnormalities including bony growths projecting from the surfaces of bones. Typically individuals with Langer–Giedion syndrome have fine scalp hair, ears that may be large or prominent, broad eyebrows, deep-set eyes, a bulbous nose, long narrow upper lip, and missing teeth.

The syndrome gets its name from the characteristic cry of affected infants, which is similar to that of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of children lose the cry by age of 2 years. Other symptoms of cri du chat syndrome may include:

- feeding problems because of difficulty in swallowing and sucking;

- low birth weight and poor growth;

- severe cognitive, speech, and motor delays;

- behavioral problems such as hyperactivity, aggression, outbursts, and repetitive movements;

- unusual facial features which may change over time;

- excessive drooling;

- small head and jaw;

- wide eyes;

- skin tags in front of eyes.

Other common findings include hypotonia, microcephaly, growth retardation, a round face with full cheeks, hypertelorism, epicanthal folds, down-slanting palpebral fissures, strabismus, flat nasal bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar creases, and cardiac defects (e.g., ventricular septal defect [VSD], atrial septal defect [ASD], patent ductus arteriosus [PDA], tetralogy of Fallot). Infertility is not associated with Cri du chat.

It has also been observed that people with the condition have difficulties communicating. While levels of proficiency can range from a few words to short sentences, it is often recommended by medical professionals for the child to undergo some sort of speech therapy/aid with the help of a professional.

Less frequently encountered findings include cleft lip and palate, preauricular tags and fistulas, thymic dysplasia, intestinal malrotation, megacolon, inguinal hernia, dislocated hips, cryptorchidism, hypospadias, rare renal malformations (e.g., horseshoe kidneys, renal ectopia or agenesis, hydronephrosis), clinodactyly of the fifth fingers, talipes equinovarus, pes planus, syndactyly of the second and third fingers and toes, oligosyndactyly, and hyperextensible joints. The syndrome may also include various dermatoglyphics, including transverse flexion creases, distal axial triradius, increased whorls and arches on digits, and a single palmar crease.

Late childhood and adolescence findings include significant intellectual disability, microcephaly, coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal bridge, severe malocclusion, and scoliosis.

Affected females reach puberty, develop secondary sex characteristics, and menstruate at the usual time. The genital tract is usually normal in females except for a report of a bicornuate uterus. In males, testes are often small, but spermatogenesis is thought to be normal.

The earliest signs and symptoms occur in newborns and consist of hypotonia, but show up in youth as developmental delays, low muscle tone, learning disabilities, being overweight, autism-like symptoms, seizures, eczema, asthma, chest and ear infections, and abnormalities in face, hands, and feet. Autism-like symptoms consist of odd obsessions, repetitive behavior, poor use of eye contact, impaired speech, poor understanding of others’ emotions, idiosyncratic use of words or phrases. People with this disorder also tend to have a characteristic appearance, including prominent forehead, thin, highly arched eyebrows, depressed nasal bridge, full cheeks, deficient nasal alae and prominent columella, thin upper lip, and various minor anomalies of the pinnae. Heart, brain, gastrointestinal, and kidney problems such as Wilms tumor, hernias, spinal curvatures, Osteopenia, hearing and sight difficulties can also occur.

It has been associated with Wilms' tumor and brachydactyly.

Proximal 18q- causes developmental disabilities. Receptive language skills tend to be more advanced and can be near normal; however, expressive language skills are usually significantly delayed.

In some children without “classic” holoprosencephaly, microforms of holoprosencephaly may be noted on MRI, including missing olfactory tracts and bulbs and absent or hypoplastic corpus callosum.

Children with proximal 18q- are often small for their age. Unlike distal 18q-, however, growth hormone deficiency has not been reported in anyone with proximal 18q-.

Jacobsen Syndrome is a rare chromosomal disorder resulting from deletion of genes from chromosome 11 that includes band 11q24.1. It is a congenital disorder. Since the deletion takes place on the q arm of chromosome 11, it is also called 11q terminal deletion disorder. The deletion may range from 5 million to 16 million deleted DNA base pairs. The severity of symptoms depends on the number of deletions. The more deletions there are more severe the symptoms are likely to be. People with Jacobsen syndrome have serious intellectual disabilities, dysmorphic features, delayed development and a variety of physical problems including heart defects. Research shows that almost 88.5% of people with Jacobsen Syndrome have a bleeding disorder called Paris-Trousseau syndrome. [ Jacobsen Syndrome is catastrophic in 1 out of every 5 cases, since children usually die within the first 2 years of life due to heart complications.

Hypotonia is a common finding. Around 10% of people with distal 18q- have seizures.

Heart abnormalities are present in 25–35% of people with distal 18q-. The majority of these defects are septal. Congenital orthopedic anomalies are also relatively common, particularly rocker-bottom feet or clubfoot. Cleft lip and palate are relatively common in people with distal 18q-. Kidney abnormalities have also been reported and include horseshoe kidney, hydronephrosis, polycystic kidney, and absent kidney. Boys with distal 18q- may have genital anomalies, the most frequent being cryptorchidism and hypospadias.

ATR-16 syndrome affects the blood, development, and brain; symptoms vary based on the specific genes deleted on chromosome 16. Because it is so rare, it is difficult to determine the "core" symptoms of the disease. People with ATR-16 have alpha-thalassemia, a blood disorder where there is less normal hemoglobin in the blood than there should be, and the red blood cells are smaller than they should be (microcytic anemia). Affected children have various characteristic physical features, including clubfoot, "locked" little fingers, microcephaly (small head), hypertelorism (widely spaced eyes), broad, prominent nose bridge, downward-slanted palpebral fissures, small ears, retrognathia, and short neck. Children with ATR-16 syndrome also have mild to moderate intellectual disabilities, developmental delays/growth delays, and speech delays. Some children with ATR-16 have seizures, cryptorchidism (undescended testes), or hypospadias.

Current research demonstrates a unique profile of speech and language impairments is associated with 22q11.2DS. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. Common problems include hypernasality, language delays, and speech sound errors.

Hypernasality occurs when air escapes through the nose during the production of oral speech sounds, resulting in reduced intelligibility. This is a common characteristic in the speech and language profile because 69% of children have palatal abnormalities. If the structure of the soft palate velum is such that it does not stop the flow of air from going up to the nasal cavity, it will cause hypernasal speech. This phenomenon is referred as velopharyngeal inadequacy (VPI). Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery.

Difficulties acquiring vocabulary and formulating spoken language (expressive language deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion. Vocabulary acquisition is often severely delayed for preschool-age children. In some recent studies, children had a severely limited vocabulary or were still not verbal at 2–3 years of age. School-age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences. Receptive language, which is the ability to comprehend, retain, or process spoken language, can also be impaired, although not usually with the same severity as expressive language impairments.

Articulation errors are commonly present in children with 22q11.2 deletion syndrome. These errors include a limited phonemic (speech sound) inventory and the use of compensatory articulation strategies resulting in reduced intelligibility. The phonemic inventory typically produced consists of sounds made in the front or back of the oral cavity such as: /p/, /w/, /m/, /n/, and glottal stops. Sound made in the middle of the mouth are completely absent. Compensatory articulation errors made by this population of children include: glottal stops, nasal substitutions, pharyngeal fricatives, linguapalatal sibilants, reduced pressure on consonant sounds, or a combination of these symptoms. Of these errors, glottal stops have the highest frequency of occurrence. It is reasoned that a limited phonemic inventory and the use of compensatory articulation strategies is present due to the structural abnormalities of the palate. The speech impairments exhibited by this population are more severe during the younger ages and show a trend of gradual improvement as the child matures.

22q13 deletion syndrome (spoken as "twenty-two q one three", see Locus (genetics)) is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. 22q13 deletion syndrome is often called Phelan-McDermid syndrome (abbreviated PMS). There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by "SHANK3" mutations, a definition that appears to exclude terminal deletions. The requirement to include "SHANK3" in the definition is supported by many, but not by those who first described 22q13 deletion syndrome.

A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small. The availability of DNA microarray technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice. The falling cost for whole exome sequencing and, eventually, whole genome sequencing, may replace DNA microarray technology for candidate evaluation. However, fluorescence in situ hybridization (FISH) tests remain valuable for diagnosing cases of mosaicism (mosaic genetics) and chromosomal rearrangements (e.g., ring chromosome, unbalanced chromosomal translocation). Although early researchers sought a monogenic (single gene genetic disorder) explanation, recent studies have not supported that hypothesis (see Etiology, below).

The clinical phenotype of 3q29 microdeletion syndrome is variable. Clinical features can include mild/moderate mental retardation with mildly dysmorphic facial features (long and narrow face, short philtrum and a high nasal bridge). Of the 6 reported patients, additional features including autism, ataxia, chest-wall deformity and long, tapering fingers were found in at least two patients. A review of 14 children with insterstitial deletions of 3q29, found 11 who had the common recurrent 1.6Mb deletion and displayed mental retardation and microcephaly.

The variability of phenotype is underscored by the report on a 6 and 9/12 year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably the patient, per formal IQ testing, was not found to have frank mental retardation as has been previously reported among patients with chromosome 3q29 terminal deletion, but rather the patient has demonstrated an average full-scale IQ result. This report further expands the phenotypic spectrum to include the possibility of normal intelligence as corroborated by formal, longitudinal psycho-educational testing.

The presence of two homologous low copy repeats either side of the deletion break-point suggests that non-allelic homologous recombination is the likely mechanism underlying this syndrome.