Though it is only definitively diagnosed by a genetic test, autosomal dominant porencephaly type I can be suspected if the disease is known to run in the family or if someone shows symptoms. CT scanning or MRI may be useful in indicating a diagnosis. COL4A1 may be mutated in other diseases that need to be distinguished, including brain small vessel disease with hemorrhage and HANAC syndrome. CADASIL syndrome is caused by a mutation in a different gene, but may cause similar symptoms. Sporadic porencephaly is another disorder that can appear similar.

Treatment for autosomal dominant porencephaly type I is based on the symptoms that an individual is experiencing - for example, treatment of seizures with anticonvulsants. It is particularly important for individuals with this disorder and hypertension to control their blood pressure, as they are at higher risk of stroke. Other stroke prevention treatments include avoiding anticoagulants, smoking, and situations that may lead to head trauma.

The standard treatment of COC is enucleation and curettage (E&C). Recurrence following E&C is rare.

In 1993, Peter James Dyck divided HSAN I further into five subtypes HSAN IA-E based on the presence of additional features. These features were thought to result from the genetic diversity of HSAN I (i.e. the expression of different genes, different alleles of a single gene, or modifying genes) or environmental factors. Molecular genetic studies later confirmed the genetic diversity of the disease.

The diagnosis of HSAN I is based on the observation of symptoms described above and is supported by a family history suggesting autosomal dominant inheritance. The diagnosis is also supported by additional tests, such as nerve conduction studies in the lower limbs to confirm a sensory and motor neuropathy. In sporadic cases, acquired neuropathies, such as the diabetic foot syndrome and alcoholic neuropathy, can be excluded by the use of magnetic resonance imaging and by interdisciplinary discussion between neurologists, dermatologists, and orthopedics.

The diagnosis of the disease has been revolutionized by the identification of the causative genes. The diagnosis is now based on the detection of the mutations by direct sequencing of the genes. Nevertheless, the accurate phenotyping of patients remains crucial in the diagnosis. For pregnant patients, termination of pregnancy is not recommended.

HSAN I must be distinguished from hereditary motor and sensory neuropathy (HMSN) and other types of hereditary sensory and autonomic neuropathies (HSAN II-V). The prominent sensory abnormalities and foot ulcerations are the only signs to separate HSAN I from HMSN. HSAN II can be differentiated from HSAN I as it is inherited as an autosomal recessive trait, it has earlier disease onset, the sensory loss is diffused to the whole body, and it has less or no motor symptoms. HSAN III-V can be easily distinguished from HSAN I because of congenital disease onset. Moreover, these types exhibit typical features, such as the predominant autonomic disturbances in HSAN III or congenital loss of pain and anhidrosis in HSAN IV.

Unilocular radiolucency may be seen and mutilocular also, and mixed too .irregular calcifications may be seen in some cases.

An OI diagnosis can be confirmed through DNA or collagen testing, but in many cases the occurrence of bone fractures with little trauma and the presence of other clinical features such as blue sclera are sufficient for a diagnosis. A skin biopsy can be performed to determine the structure and quantity of type I collagen. DNA testing can confirm the diagnosis, however, it cannot exclude it because not all mutations causing OI are known and/or tested for. OI type II is often diagnosed by ultrasound during pregnancy, where already multiple fractures and other characteristic features may be present. Relative to control, OI cortical bone shows increased porosity, canal diameter, and connectivity in micro-computed tomography.

An important differential diagnosis of OI is child abuse, as both may present with multiple fractures in various stages of healing. Differentiating them can be difficult, especially when no other characteristic features of OI are present. Other differential diagnoses include rickets, osteomalacia, and other rare skeletal syndromes.

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.

Phakomatosis pigmentovascularis is a rare neurocutanous condition where there is coexistence of a capillary malformation (port-wine stain) with various melanocytic lesions, including dermal melanocytosis (Mongolian spots), nevus spilus, and nevus of Ota.

More than 1 in 2 people with OI also have dentinogenesis imperfecta (DI) - a congenital disorder of formation of dentine. Dental treatment may pose as a challenge as a result of the various deformities, skeletal and dental, due to OI. Children with OI should go for a dental check-up as soon as their teeth erupt, this may minimize tooth structure loss as a result of abnormal dentine, and they should be monitored regularly to preserve their teeth and oral health.

Genetic changes are related to the following types of collagenopathy, types II and XI.

The system for classifying collagenopathies is changing as researchers learn more about the genetic causes of these disorders.The clinical features of the type II and XI collagenopathies vary among the disorders, but there is considerable overlap. Common signs and symptoms include problems with bone development that can result in short stature, enlarged joints, spinal curvature, and arthritis at a young age. For some people, bone changes can be seen only on X-ray images. Problems with vision and hearing, as well as a cleft palate with a small lower jaw, are common. Some individuals with these disorders have distinctive facial features such as protruding eyes and a flat nasal bridge.

Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.

Niemann–Pick type C is diagnosed by assaying cultured fibroblasts for cholesterol esterfication and staining for unesterified cholesterol with filipin. The fibroblasts are grown from a small skin biopsy taken from a patient with suspected NPC. The diagnosis can be confirmed by identifying mutations in the NPC1 or NPC2 genes in 80–90% of cases. This specialized testing is available at Thomas Jefferson University Lysosomal Disease Testing Lab and the Mayo Clinic.

The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity to connective tissue. Type II and type XI collagen disorders are grouped together because both types of collagen are components of the cartilage found in joints and the spinal column, the inner ear, and the jelly-like substance that fills the eyeball (the vitreous). The type II and XI collagenopathies result in similar clinical features.

Phakomatosis pigmentovascularis is subdivided into five types:

- Type 1 PWS + epidermal nevus

- Type 2 (most common): PWS + dermal melanocytosis +/- nevus anemicus

- Type 3: PWS + nevus spilus +/- nevus anemicus

- Type 4: PWS + nevus spilus + dermal melanocytosis +/- nevus anemicus

- Type 5: CMTC (Cutis marmorata telangiectatica congenita) + dermal melanocytosis

They all can contain capillary malformation. Type 2 is the most common and can be associated with granular cell tumor. Some further subdivide each type into categories A & B; with A representing oculocutaneous involvement and subtype B representing extra oculocutaneous involvement. Others have proposed fewer subtypes but currently this rare entity is mostly taught as having five subtypes currently.

Three main points in diagnosing thumb hypoplasia are: width of the first web space, instability of the involved joints and function of the thumb. Thorough physical examination together with anatomic verification at operation reveals all the anomalies. An X-ray of the hand and thumb in two directions is always mandatory. When the pediatrician thinks the condition is associated with some kind of syndrome other tests will be done. More subtle manifestations of types I and II may not be recognized, especially when more obvious manifestations of longitudinal radial deficiency in the opposite extremity are present. Therefore, a careful examination of both hands is important.

In terms of diagnosis for this condition, the following methods/tests are available:

- Endoscopic

- CT scan

- Serum endocrine autoantibody screen

- Histologic test

No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in PMI-CDG (CDG-Ib) for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG (CDG-IIc or LAD-II) patients.

Infants with achondrogenesis, type 2 have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Achondrogenesis, type 2 is a subtype of collagenopathy, types II and XI. This condition is also associated with a lack of bone formation (ossification) in the spine and pelvis. Typical facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis in which excess fluid builds up in the body before birth. The skull bones may be soft, but they often appear normal on X-ray images. In contrast, bones in the spine (vertebrae) and pelvis do not harden.

Achondrogenesis, type 2 and hypochondrogenesis (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 births. Achondrogenesis, type 2 is one of several skeletal disorders caused by mutations in the "COL2A1" gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other tissues that form the body's supportive framework (connective tissues). Mutations in the "COL2A1" gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.

Achondrogenesis, type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. The disorder is not passed on to the next generation, however, because affected individuals hardly survive past puberty.

It has several different types:

- type 1 - Apert syndrome

- type 2 - Crouzon syndrome

- type 3 - Saethre-Chotzen syndrome

- type 5 - Pfeiffer syndrome

A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation. It also has multiple types:

- type 1 - Noack syndrome; now classified with Pfeiffer syndrome

- type 2 - Carpenter syndrome

- type 3 - Sakati-Nyhan-Tisdale syndrome

- type 4 - Goodman syndrome; now classified with Carpenter syndrome

- type 5 - Pfeiffer syndrome

It has been suggested that the distinction between "acrocephalosyndactyly" versus "acrocephalopolysyndactyly" should be abandoned.

The lifespan of patients with NPC is usually related to the age of onset. Children with antenatal or infantile onset usually succumb in the first few months or years of life, whereas adolescent and adult onset forms of Niemann–Pick type C have a more insidious onset and slower progression, and affected individuals may survive to the seventh decade. Adult cases of NPC are being recognized with increasing frequency. It is suspected that many patients affected by NPC are undiagnosed, owing to lack of awareness of the disease and the absence of readily available screening or diagnostic tests. For the same reasons the diagnosis is often delayed by many years.

Acrocephalosyndactylia (or acrocephalosyndactyly) is the common presentation of craniosynostosis and syndactyly.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

Niemann–Pick Type B involves an enlarged liver and spleen hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cells involved in clotting (platelets). The brain is not affected in Type B and the disease often presents in the pre-teen years.

When it comes to treatment it is important to differentiate a thumb that needs stability, more web width and function, or a thumb that needs to be replaced by the index finger. Severe thumb hypoplasia is best treated by pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by first web space release, ligament reconstruction and muscle or tendon transfer.

It has been recommended that pollicization is performed before 12 months, but a long-term study of pollicizations performed between the age of 9 months and 16 years showed no differences in function related to age at operation.

It is important to know that every reconstruction of the thumb never gives a normal thumb, because there is always a decline of function. When a child has a good index finger, wrist and fore-arm the maximum strength of the thumb will be 50% after surgery in comparison with a normal thumb. The less developed the index finger, wrist and fore-arm is, the less strength the reconstructed thumb will have after surgery.