Two key features of AOS are aplasia cutis congenita with or without underlying bony defects and terminal transverse limb defects. Cutis aplasia congenita is defined as missing skin over any area of the body at birth; in AOS skin aplasia occurs at the vertex of the skull. The size of the lesion is variable and may range from solitary round hairless patches to complete exposure of the cranial contents. There are also varying degrees of terminal limb defects (for example, shortened digits) of the upper extremities, lower extremities, or both. Individuals with AOS may have mild growth deficiency, with height in the low-normal percentiles. The skin is frequently observed to have a mottled appearance (cutis marmorata telangiectatica congenita). Other congenital anomalies, including cardiovascular malformations, cleft lip and/or palate, abnormal renal system, and neurologic disorders manifesting as seizure disorders and developmental delay are sometimes observed. Variable defects in blood vessels have been described, including hypoplastic aortic arch, middle cerebral artery, pulmonary arteries. Other vascular abnormalities described in AOS include absent portal vein, portal sclerosis, arteriovenous malformations, abnormal umbilical veins, and dilated renal veins.

Gerodermia osteodysplastica is characterized by symptoms and features which affect the connective tissues, skin and skeletal system.

These are: wrinkly, loose skin over the face, abdomen, and extremites (hands, feet) on the dorsal sides usually worsened by chronic joint laxity and hyperextensibility; fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers; osteopenia and osteoporosis, with associated fractures; malar hypoplasia (underdeveloped cheek bone), maxillary hypoplasia (underdeveloped upper jaw), mandibular prognathism (protrusion of the lower jaw and chin), bowed long bones, platyspondyly (flattened spine) related to vertebral collapse; kyphoscoliosis (scoliosis with kyphosis, or "hunch back"), metaphyseal peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal region of the bone, near the knee); and the overall physical effects and facial appearance of dwarfism with premature aging.

Other features and findings include: intrauterine growth retardation, congenital hip dislocations, winged scapulae (shoulder blades), pes planus (fallen arches), pseudoepiphyses of the second metacarpals (upper bone of the fingers), hypotelorism (close-set eyes), malformed ears,

developmental delay,

failure to thrive and abnormal electroencephalograph (EEG) readings.

Dental and orthodontal abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including malocclusion of the dental arches (the maxilla and mandible), radiological findings in some cases have indicated significant overgrowth of the mandibular premolar and molar roots;

hypercementosis (overproduction of cementum) of the molars and maxillary incisors; enlarged, funnel-shaped mandibular lingula (spiny structures on the ramus of the mandible); and a radiolucent effect on portions of many teeth, increasing their transparency to x-rays.

Signs and symptoms of this disorder include weak muscle tone (hypotonia), sagging facial features, seizures, intellectual disability, and developmental delay. The patients have brittle hair and metaphyseal widening. In rare cases, symptoms begin later in childhood and are less severe. Affected infants may be born prematurely. Symptoms appear during infancy and are largely a result of abnormal intestinal copper absorption with a secondary deficiency in copper-dependent mitochondrial enzymes. Normal or slightly slowed development may proceed for 2 to 3 months, and then there will be severe developmental delay and a loss of early developmental skills. Menkes Disease is also characterized by seizures, failure to thrive, subnormal body temperature, and strikingly peculiar hair, which is kinky, colorless or steel-colored, and easily broken. There can be extensive neurodegeneration in the gray matter of the brain. Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures.

Occipital horn syndrome (sometimes called X-linked cutis laxa or Ehlers-Danlos type 9) is a mild form of Menkes syndrome that begins in early to middle childhood. It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, loose skin, and joints.

This condition is characterised by symmetrical lesions on the temples resembling forceps marks. It is characterized a puckered skin due to a virtual absence of subcutaneous fat. It is apparent at birth. Other lesions that may be present include puffy, wrinkled skin around the eyes and/or abnormalities of the eyelashes, eyebrows, and eyelids. The eyebrows may be up slanting or outward slanting. Occasionally the bridge of the nose may appear flat, while the tip may appear unusually rounded. The chin may be furrowed. The upper lip may be prominent with a down turned mouth. Other features that have been reported include dysplastic and low set ears, linear radiatory impressions on the forehead and congenital horizontal nystagmus.

Those with the Setleis syndrome may be missing eyelashes on both the upper and lower lids or may have multiple rows of lashes on the upper lids but none on the lower lids.A possible association with intra abdominal cancer has been reported but to date this has not been confirmed in other studies.

The skin lesions evolve through characteristic stages:

1. blistering (from birth to about four months of age),

2. a wart-like rash (for several months),

3. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by

4. linear hypopigmentation.

Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.

Discolored skin is caused by excessive deposits of melanin (normal skin pigment).

Most newborns with IP will develop discolored skin within the first two weeks.

The pigmentation involves the trunk and extremities, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines.

The discoloration sometimes fades with age.

Neurological problems can include: cerebral atrophy, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex.

About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, mental retardation, and seizures.

They are also likely to have visual problems, which can include: crossed eyes, cataracts, and severe visual loss.

Dental problems are common, and include missing or peg-shaped teeth - patients with IP often keep milk teeth into adult life.

Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia and supernumerary nipples.

Skeletal and structural anomalies can occur in approximately 14% of patients, including:

- Somatic asymmetry,

- Hemivertebrae,

- Scoliosis,

- Spina bifida,

- Syndactyly,

- Acheiria (congenital absence of the hands - note: other limbs may be affected),

- Ear anomalies,

- Extra ribs,

- Skull deformities,

- Primary pulmonary hypertension,

- Cardiopulmonary failure

Theoretically, a mutation in any of the may cause disease, but below are some notable ones, with short description of symptoms:

- Adrenoleukodystrophy; leads to progressive brain damage, failure of the adrenal glands and eventually death.

- Alport syndrome; glomerulonephritis, endstage kidney disease, and hearing loss.

- Androgen insensitivity syndrome; variable degrees of undervirilization and/or infertility in XY persons of either gender

- Barth syndrome; metabolism distortion, delayed motor skills, stamina deficiency, hypotonia, chronic fatigue, delayed growth, cardiomyopathy, and compromised immune system.

- Blue cone monochromacy; low vision acuity, color blindness, photophobia, infantile nystagmus.

- Centronuclear myopathy; where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.

- Charcot–Marie–Tooth disease (CMTX2-3); disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease.

- Coffin–Lowry syndrome; severe mental retardation sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis as well as auditory and visual abnormalities.

- Fabry disease; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement.

- Hunter's Syndrome; potentially causing hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen.

- Hypohidrotic ectodermal dysplasia, presenting with hypohidrosis, hypotrichosis, hypodontia

- Kabuki syndrome; multiple congenital anomalies and mental retardation.

- Spinal and bulbar muscular atrophy; muscle cramps and progressive weakness

- Lesch-Nyhan syndrome; neurologic dysfunction, cognitive and behavioral disturbances including self-mutilation, and uric acid overproduction (hyperuricemia)

- Lowe Syndrome; hydrophthalmia, cataracts, intellectual disabilities, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets

- Menkes disease; sparse and coarse hair, growth failure, and deterioration of the nervous system

- Nasodigitoacoustic syndrome; mishaped nose, brachydactyly of the distal phalanges, sensorineural deafness

- Nonsyndromic deafness; hearing loss

- Norrie disease; cataracts, leukocoria along with other developmental issues in the eye

- Occipital horn syndrome; deformations in the skeleton

- Ocular albinism; lack of pigmentation in the eye

- Ornithine transcarbamylase deficiency; developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen

- Siderius X-linked mental retardation syndrome; cleft lip and palate with mental retardation and facial dysmorphism, caused by mutations in the histone demethylase PHF8

- Simpson-Golabi-Behmel syndrome; coarse faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip

- Spinal muscular atrophy caused by UBE1 gene mutation; weakness due to loss of the motor neurons of the spinal cord and brainstem

- Wiskott-Aldrich syndrome; eczema, thrombocytopenia, immune deficiency, and bloody diarrhea

- X-linked Severe Combined Immunodeficiency (SCID); infections, usually causing death in the first years of life

- X-linked sideroblastic anemia; skin paleness, fatigue, dizziness and enlarged spleen and liver.

Gerodermia osteodysplastica (GO), also called geroderma osteodysplasticum and Walt Disney dwarfism, is a rare autosomal recessive connective tissue disorder included in the spectrum of cutis laxa syndromes.

Usage of the name "Walt Disney dwarfism" is attributed to the first known case of the disorder, documented in a 1950 journal report, in which the authors described five affected members from a Swiss family as having the physical appearance of dwarves from a Walt Disney film.

The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end.

SFMS affects the skeletal and nervous system. This syndrome's external signs would be an unusual facial appearance with their heads being slightly smaller and unusually shaped, a narrow face which is also called dolichocephaly, a large mouth with a drooping lower lip that are held open, protruding upper jaw, widely spaced upper front teeth, an underdeveloped chin, cleft palate and exotropied-slanted eyes with drooping eyelids.

Males who have SFMS have short stature and a thin body build. Also skin is lightly pigmented with multiple freckles. They may have scoliosis and chest abnormalities.

Affected boys have reduced muscle tone as infants and young children. X-rays sometimes show that their bones are underdeveloped and show characteristics of younger bones of children. Boys usually under the age of 10 have reduced muscle tone but later, patients with SFMS over the age of 10 have increased muscle tone and reflexes that cause spasticity. Their hands are short with unusual palm creases with short, shaped fingers and foot abnormalities are shortened and have fused toes and usually mild.

They have an absent of a spleen and the genitals may also show undescended testes ranging from mild to severe that leads to female gender assignment.

People who have SFMS have severe mental retardation. They are sometimes restless, behavior problems, seizures and severe delay in language development. They are self-absorbed with reduced ability to socialize with others around them. They also have psychomotor retardation which is the slowing-down of thoughts and a reduction of physical movements. They have cortical atrophy or degeneration of the brain's outer layer. Cortical atrophy is usually founded in older affected people.

The symptoms of blue diaper syndrome could include irritability, constipation, poor appetite, vomiting, and poor growth. Some children experience frequent fevers and intestinal infections.

Hypercalcemia could be a potential issue in affected children. Some children with blue diaper syndrome have eye or vision issues, particularly underdeveloped portions of the eye, including the cornea and optic disc.

This condition occurs almost exclusively in males. The mutation may be spontaneous or inherited from the mother. The typical clinical features are:

- flat nasal tip

- short columella

- maxillary hypoplasia

- involvement of terminal phalanges

- stippled chondrodystrophy

Most children with Allan–Herndon–Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan–Herndon–Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.

Beare–Stevenson cutis gyrata syndrome is a rare genetic disorder characterized by craniosynostosis (premature fusion of certain bones of the skull, sometimes resulting in a characteristic 'cloverleaf skull'; further growth of the skull is prevented, and therefore the shape of the head and face is abnormal) and a specific skin abnormality, called cutis gyrata, characterized by a furrowed and wrinkled appearance (particularly in the face and on the palms and soles of the feet); thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the groin.

Additional signs and symptoms of Beare–Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), overgrowth of the umbilical stump, and abnormalities of the genitalia and anus. The medical complications associated with this condition are often severe and may well be life-threatening in infancy or early childhood.

Adams–Oliver syndrome (AOS) is a rare congenital disorder characterized by defects of the scalp and cranium (cutis aplasia congenita), transverse defects of the limbs, and mottling of the skin.

De Barsy syndrome is a rare autosomal recessive genetic disorder. Symptoms include cutis laxa (loose hanging skin) as well as other eye, musculoskeletal, and neurological abnormalities. It is usually progressive, manifesting side effects that can include clouded corneas, cataracts, short stature, dystonia, or progeria (premature aging).

It was first described in 1967 by De Barsy et al. and, as of 2011, there have been 27 cases reported worldwide. The genes that cause De Barsy syndrome have not been identified yet, although several studies have narrowed down the symptoms' cause. A study by Reversade et al. has shown that a mutation in PYCR1, the genetic sequence that codes for mitochondrial enzymes that break down proline, are prevalent in cases of autosomal recessive cutis laxa (ARCL), a condition very similar to De Barsy syndrome. A study by Leao-Teles et al. has shown that De Barsy syndrome may be related to mutations in ATP6V0A2 gene, known as ATP6V0A2-CDG by the new naming system.

Alternative names for De Barsy syndrome include corneal clouding-cutis laxa-mental retardation, cutis laxa-growth deficiency syndrome, De Barsy–Moens–Diercks syndrome, and progeroid syndrome of De Barsy.

X-linked recessive chondrodysplasia punctata is a type of chondrodysplasia punctata that can involve the skin, hair, and cause short stature with skeletal abnormalities, cataracts, and deafness.

This condition is also known as arylsulfatase E deficiency, CDPX1, and X-linked recessive chondrodysplasia punctata 1. The syndrome rarely affects females, but they can be carriers of the recessive allele. Although the exact number of people diagnosed with CDPX1 is unknown, it was estimated that 1 in 500,000 have CDPX1 in varying severity. This condition is not linked to a specific ethnicity. The mutation that leads to a deficiency in arylsulfatase E. (ARSE) occurs in the coding region of the gene.Absence of stippling, deposits of calcium, of bones and cartilage, shown on x-ray, does not rule out chondrodysplasia punctata or a normal chondrodysplasia punctata 1 (CDPX1) gene without mutation. Stippling of the bones and cartilage is rarely seen after childhood. Phalangeal abnormalities are important clinical features to look for once the stippling is no longer visible. Other, more severe, clinical features include respiratory abnormalities, hearing loss, cervical spine abnormalities, delayed cognitive development, ophthalmologic abnormalities, cardiac abnormalities, gastroesophageal reflux, and feeding difficulties. CDPX1 actually has a spectrum of severity; different mutations within the CDPX1 gene have different effects on the catalytic activity of the ARSE protein. The mutations vary between missense, nonsense, insertions, and deletions.

Symptoms of M2DS include infantile hypotonia and failure to thrive, delayed psychomotor development, impaired speech, abnormal or absent gait, epilepsy, spasticity, gastrointestinal motility problems, recurrent infections, and genitourinary abnormalities. Many of those affected by M2DS also fit diagnostic criteria for autism. M2DS can be associated with syndromic facies, namely an abnormally flat back of the head, underdevelopment of the midface, ear anomalies, deep-set eyes, prominent chin, pointed nose, and a flat nasal bridge.

Incontinentia pigmenti (IP) is a rare genetic disorder that affects the skin, hair, teeth, nails, and central nervous system. It is named from its appearance under a microscope. It is also known as Bloch–Siemens syndrome, Bloch–Sulzberger disease, Bloch–Sulzberger syndrome, melanoblastosis cutis, and nevus pigmentosus systematicus.

It is characterized by skin abnormalities that begin in childhood, usually a blistering rash which heals, followed by the development of harder skin growths. The skin may develop grey or brown patches which fade with time. Other symptoms can include hair loss, dental abnormalities, eye abnormalities that can lead to vision loss, and lined or pitted fingernails and toenails. Associated problems can include delayed development, intellectual disability, seizures, and other neurological problems. There is no specific treatment, individual conditions must be managed by specialists.

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.

Lenz–Majewski syndrome is a skin condition characterized by hyperostosis, craniodiaphyseal dysplasia, dwarfism, cutis laxa, proximal symphalangism, syndactyly, brachydactyly, mental retardation, enamel hypoplasia, and hypertelorism.

In 2013, whole-exome sequencing showed that a missense mutation resulting in overactive phosphatidylserine synthase 1 was the cause of LMS, making it the first known human disease to be caused by disrupted phosphatidylserine metabolism. The researchers suggested a link between the condition and bone metabolism.

It is characterized by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints are loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients also present with whites of the eyes that are blue.

Aplasia cutis congenita (ACC) is a rare disorder characterized by congenital absence of skin. Frieden classified ACC in 1986 into 9 groups on the basis of location of the lesions and associated congenital anomalies. The scalp is the most commonly involved area with lesser involvement of trunk and extremities. Frieden classified ACC with fetus papyraceus as type 5. This type presents as truncal ACC with symmetrical absence of skin in stellate or butterfly pattern with or without involvement of proximal limbs.]It is the most common congenital cicatricial alopecia, and is a congenital focal absence of epidermis with or without evidence of other layers of the skin.

The exact etiology of ACC is still unclear but intrauterine infection by varicella or herpes virus, drugs such as methimazole, misoprostol, valproate, cocaine, marijuana etc., fetus papyraceus, feto-fetal transfusion, vascular coagulation defects, amniotic membrane adherence, abnormal elastic fiber biomechanical forces and trauma are implicated. It can be associated with Johanson-Blizzard syndrome, Adams-Oliver syndrome, trisomy 13, and Wolf-Hirschhorn syndrome.

It can also seen with exposure to methimazole and carbimazole in utero. This dermatological manifestation has been linked to Peptidase D haploinsufficiency and a deletion in Chromosome 19.

SCARF syndrome is a rare syndrome characterized by skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, retardation, and facial abnormalities. It shares some features with Lenz-Majewski hyperostotic dwarfism syndrome.

Blue diaper syndrome is a rare, autosomal recessive metabolic disorder characterized in infants by bluish urine-stained diapers. It is also known as Drummond's syndrome, and hypercalcemia.

It is caused by a defect in tryptophan absorption. Bacterial degradation of unabsorbed tryptophan in the intestine leads to excessive indole production and thus to indicanuria which, on oxidation to indigo blue, causes a peculiar bluish discoloration of the diaper (indoluria). Symptoms typically include digestive disturbances, fever and visual problems. Some may also develop disease due to the incomplete breakdown of tryptophan.

It was characterized in 1964, and is associated with the X linked sex gene.

Since this syndrome is X linked, the chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Parents can undergo genetic testing to see if their child will get this syndrome, but most do not find out until they see the symptoms mentioned below.

Focal facial dermal dysplasia (FFDD) is a rare genetically heterogeneous group of disorders that are characterized by congenital bilateral scar like facial lesions, with or without associated facial anomalies. It is characterized by hairless lesions with fingerprint like puckering of the skin, especially at the temples, due to alternating bands of dermal and epidermal atrophy.

This condition is also known as Brauer syndrome (hereditary symmetrical aplastic nevi of temples, bitemporal aplasia cutis congenita, bitemporal aplasia cutis congenita: OMIM ) and Setleis syndrome (facial ectodermal dysplasia: OMIM ).

Affected males develop generalized reticular hyper pigmentation in early childhood.

Hair often looks bedraggled or brushed backwards, hanging low on the forehead.

Among the associated extracutaneous manifestations are described:

- Respiratory infections

- Dyskeratosis corneal photophobia

- Hypohidrosis with large deficit of thermoregulation

- Growth retardation

- Gastrointestinal disorders

- Kidney disease

- Kidney stones

- Urinary infections

- Webbed feet or hands

- Electrolyte imbalance

- Retinitis pigmentosa

- Lymphoedema

- Thyroid abnormalities

Each patient shows some of the symptoms listed above. Not every sick person will show all of the listed symptoms.

In females the disease is characterized by skin rashes linear hyper pigmentation following the Blaschko's lines, morphologically similar to stage 3 pigment incontinence. There are no systemic manifestations associated with XLPDR in females.