Osteomyelitis (bone infection), which is much more common than infantile cortical hyperostosis, must be excluded, since it requires urgent treatment. Other diagnoses that can mimic this disorder and need to be excluded include physical trauma, child abuse, Vitamin A excess, hyperphosphatemia, prostaglandin E1 and E2 administration, scurvy, infections (including syphilis), Ewing sarcoma, and metastatic neuroblastoma.

Most infants with infantile cortical hyperostosis are diagnosed by physical examination. X-rays can confirm the presence of bone changes and soft tissue swelling. Biopsy of the affected areas can confirm the presence of typical histopathological changes. No specific blood tests exist, but tests such as erythrocyte sedimentation rate (ESR) and alkaline phosphatase levels are often elevated. A complete blood count may show anemia (low red blood cell count) and leukocytosis (high white blood cell count). Other tests may be done to help exclude other diagnoses. Ultrasound imaging can help diagnose prenatal cases.

Craniometaphyseal dysplasia is diagnosed based on clinical and radiographic findings that include hyperostosis. Some things such as cranial base sclerosis and nasal sinuses obstruction can be seen during the beginning of the child's life. In radiographic findings the most common thing that will be found is the narrowing of foramen magnum and the widening of long bones. Once spotted treatment is soon suggested to prevent further compression of the foramen magnum and disabling conditions.

The only treatment for this disorder is surgery to reduce the compression of cranial nerves and spinal cord. However, bone regrowth is common since the surgical procedure can be technically difficult. Genetic counseling is offered to the families of the people with this disorder.

Once the diagnosis of polymicrogyria has been established in an individual, the following approach can be used for discussion of prognosis:

A pregnancy history should be sought, with particular regard to infections, trauma, multiple gestations, and other documented problems. Screening for the common congenital infections associated with polymicrogyria with standard TORCH testing may be appropriate. Other specific tests targeting individual neurometabolic disorders can be obtained if clinically suggested.

The following may help in determining a genetic etiology:

Family history

It is important to ask for the presence of neurologic problems in family members, including seizures, cognitive delay, motor impairment, pseudobulbar signs, and focal weakness because many affected family members, particularly those who are older, may not have had MRI performed, even if these problems came to medical attention. In addition, although most individuals with polymicrogyria do present with neurologic difficulties in infancy, childhood, or adulthood, those with mild forms may have no obvious deficit or only minor manifestations, such as a simple lisp or isolated learning disability. Therefore, if a familial polymicrogyria syndrome is suspected, it may be reasonable to perform MRI on relatives who are asymptomatic or have what appear to be minor findings. The presence of consanguinity in a child's parents may suggest an autosomal recessive familial polymicrogyria syndrome.

Physical examination

A general physical examination of the proband may identify associated craniofacial, musculoskeletal, or visceral malformations that could indicate a particular syndrome. Neurologic examination should assess cognitive and mental abilities, cranial nerve function, motor function, deep tendon reflexes, sensory function, coordination, and gait (if appropriate).

Genetic testing

Myeolography, including post-myelographic CT is likely the most effective imaging study an accurate diagnosis.

Parents of a proband

- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.

- Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

- At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

- Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3.

- Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

- Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele.

- In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.

Other family members of a proband.

- Each sibling of the proband's parents is at a 50% risk of being a carrier

Surgical management options include extensive cervical laminectomy with or without an additional posterior arthrodesis, anterior decompression and arthrodesis, and posterior cervical laminoplasty. Treatment decisions can be made based on a grading systems devised by Hirabayashi et al., supplemented by the Nurick myelopathy classification system.

The diagnosis is usually based on clinical features present at birth.

Ultrasound in the second trimester may show abnormalities associates with NLS, including polyhydramnios, intrauterine growth restriction, microcephaly, proptosis and decreased fetal motility.

The prognosis is poor; affected individuals are either stillborn or die shortly after birth. The longest survival reported in literature is of 134 days.

This syndrome is transmitted as an autosomal recessive disorder and there is a risk for recurrence of 25% in future pregnancies.

Sclerosteosis is caused by mutations in the gene that encode for the sclerostin protein.

Sclerosteosis is an autosomal recessive disorder characterized by bone overgrowth. It was first described in 1958 but given the current name in 1967. Excessive bone formation is most prominent in the skull, mandible and tubular bones. It can cause facial distortion and syndactyly. Increased intracranial pressure can cause sudden death in patients. It is a rare disorder that is most prominent in the Afrikaner population in South Africa (40 patients), but there have also been cases of American and Brazilian families.

There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity. Some degree of developmental delay is expected in almost all cases of M-CM, so evaluation for early intervention or special education programs is appropriate. Rare cases have been reported with no discernible delay in academic or school abilities.

Physical therapy and orthopedic bracing can help young children with gross motor development. Occupational therapy or speech therapy may also assist with developmental delays. Attention from an orthopedic surgeon may be required for leg length discrepancy due to hemihyperplasia.

Children with hemihyperplasia are thought to have an elevated risk for certain types of cancers. Recently published management guidelines recommend regular abdominal ultrasounds up to age eight to detect Wilms' tumor. AFP testing to detect liver cancer is not recommended as there have been no reported cases of hepatoblastoma in M-CM patients.

Congenital abnormalities in the brain and progressive brain overgrowth can result in a variety of neurological problems that may require intervention. These include hydrocephalus, cerebellar tonsillar herniation (Chiari I), seizures and syringomyelia. These complications are not usually congenital, they develop over time often presenting complications in late infancy or early childhood, though they can become problems even later. Baseline brain and spinal cord MRI imaging with repeat scans at regular intervals is often prescribed to monitor the changes that result from progressive brain overgrowth.

Assessment of cardiac health with echocardiogram and EKG may be prescribed and arrhythmias or abnormalities may require surgical treatment.

The only effective line of treatment for malignant infantile osteopetrosis is hematopoietic stem cell transplantation. It has been shown to provide long-term disease-free periods for a significant percentage of those treated; can impact both hematologic and skeletal abnormalities; and has been used successfully to reverse the associated skeletal abnormalities.

Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure - nevertheless, primary graft failure can prove fatal.

Worth syndrome is caused by a mutation in the LRP5 gene, located on human chromosome 11q13.4. The disorder is inherited in an autosomal dominant fashion. This indicates that the defective gene responsible for a disorder is located on an autosome (chromosome 11 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.

Worth syndrome, also known as benign form of Worth hyperostosis corticalis generalisata with torus platinus, autosomal dominant osteosclerosis, autosomal dominant endosteal hyperostosis or Worth disease, is a rare autosomal dominant congenital disorder that is caused by a mutation in the LRP5 gene. It is characterized by increased bone density and benign bony structures on the palate.

The differential diagnosis of malignant infantile osteopetrosis includes other genetic skeletal dysplasias that cause osteosclerosis. They are collectively known as osteosclerosing dysplasias. The differential diagnosis of genetic osteosclerosing dysplasias including infantile osteopetrosis has been tabulated and illustrated in literature citations.

- Neuropathic infantile osteopetrosis

- Infantile osteopetrosis with renal tubular acidosis

- Infantile osteopetrosis with immunodeficiency

- IO with leukocyte adhesion deficiency syndrome (LAD-III)

- Intermediate osteopetrosis

- Autosomal dominant osteopetrosis (Albers-Schonberg)

- Pyknodysostosis (osteopetrosis acro-osteolytica)

- Osteopoikilosis (Buschke–Ollendorff syndrome)

- Osteopathia striata with cranial sclerosis

- Mixed sclerosing bone dysplasia

- Progressive diaphyseal dysplasia (Camurati–Engelmann disease)

- SOST-related sclerosing bone dysplasias

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.

The treatment for CGCG is thorough curettage. A referral is made to an oral surgeon. Recurrence ranges from 15%–20%. In aggressive tumors, three alternatives to surgery are undergoing investigation:

- corticosteroids;

- calcitonin (salmon calcitonin);

- interferon α-2a.

These therapeutic approaches provide positive possible alternatives for large lesions. The long term prognosis of giant-cell granulomas is good and metastases do not develop.

Microlissencephaly can be diagnosed by prenatal MRI. MRI is better than ultrasound when it comes to detecting microlissencephaly or MSGP prenatally.

The ideal time for proper prenatal diagnosis is between the 34th and 35th gestational week which is the time when the secondary gyration normally terminates. In microlissencephaly cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.

At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered microlissencephaly.

Although genetic diagnosis in patients with MLIS is challenging, exome sequencing has been suggested to be a powerful diagnostic tool.

The key problem is the early fusion of the skull, which can be corrected by a series of surgical procedures, often within the first three months after birth. Later surgeries are necessary to correct respiratory and facial deformities.

The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.

Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.

Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.

Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.

Although no cause has been officially confirmed, researchers speculate the disease might result from a genetic mutation that sporadically occurs for unknown reasons.

Prognosis varies widely depending on severity of symptoms, degree of intellectual impairment, and associated complications. Because the syndrome is rare and so newly identified, there are no long term studies.

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