Familial dysbetalipoproteinemia or type III hyperlipoproteinemia (also known as remnant hyperlipidemia, "remnant hyperlipoproteinaemia", "broad beta disease" and "remnant removal disease") is a condition characterized by increased total cholesterol and triglyceride levels, and decreased HDL levels.

This condition is caused by a mutation in apolipoprotein E (ApoE), that serves as a ligand for the liver receptors for chylomicrons, IDL and VLDL or Very Low Density lipoprotein receptors. The normal ApoE turns into the defective ApoE2 form due to a genetic mutation. This defect prevents the normal metabolism of chylomicrons, IDL and VLDL, otherwise known as remnants, and therefore leads to accumulation of cholesterol within scavenger cells (macrophages) to enhance development and acceleration of atherosclerosis.

Until recently, doctors have diagnosed patients with FHS based on clinical observations and how well they fit the disease description, usually occurring in early childhood. Molecular genetic testing is also used now to test for genetic mutations. By performing a sequence analysis test of select exons, mutations can be detected in exon 34 of the SRCAP gene. This mutation has been observed in 19 patients to date.

In most cases, if the patient shows classic facial features of FHS, the molecular testing will show a mutation on the SRCAP gene.

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

FHS shares some common features with Rubinstein–Taybi (due to overlapping effects of mutations on SRCAP), however cranial and hand anomalies are distinctive: broad thumbs, narrow palate, and microcephaly are absent in Floating-Harbor Syndrome. One child in the UK has a diagnosis of microcephaly alongside Floating–Harbor syndrome.

The diagnosis of Mulibrey nanism can be done via genetic testing, as well as by the physical characteristics (signs/symptoms) displayed by the individual.

Immunodeficiency is a consistent feature with low serum concentrations of immunoglobulins which may improve with age and a poor immunological response to childhood vaccination. T cell dysfunction and abnormal antibody generation have been reported.

Microscopic analysis of the hair shows twisted hairs of unequal size and different shapes (pili torti, aniso- and poikilotrichosis), longitudinal breaks and breaks located at nodes (trichorrhexis nodosa). Scanning electron microscopy might reveal hair budding (trichorrhexis blastysis). Biochemical analysis may reveal sulfur-deficient brittle hair (trichothiodystrophy; note that disulfide bonds determine hair waviness).

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

Elevated IgE is the hallmark of HIES. An IgE level greater than 2,000 IU/mL is often considered diagnostic. However, patients younger than 6 months of age may have very low to non-detectable IgE levels. Eosinophilia is also a common finding with greater than 90% of patients having eosinophil elevations greater than two standard deviations above the normal mean. Genetic testing is available for "STAT3" (Job's Syndrome), "DOCK8 (DOCK8 Immunodeficiency or DIDS)", "PGM3" (PGM3 deficiency), "SPINK5" (Netherton Syndrome - NTS), and "TYK2" genetic defects.

Most patients with hyper IgE syndrome are treated with long-term antibiotic therapy to prevent staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.

The diagnosis CFND is established only after the presence of a mutation in the EFNB1 gene has been determined. Physical manifestations are not necessarily part of the diagnostic criteria, but can help guide in the right direction. This is due to the large heterogeneity between patients regarding phenotypic expression.

20% of the patients that present with CFND-like characteristics do not display a mutation in the EFNB1 gene. The group of patients diagnosed with CFND is thus often overestimated. However, it is important to distinguish this population from CFND for research purposes. On the other hand, especially in males, it is possible that someone is a carrier of the EFNB1 gene mutation yet does not present with any physical manifestations. Screening for the presence of an EFNB1 mutation is thus the most reliable method to establish the diagnosis CFND.

Genetic counseling or prenatal screening may be advised if there is a reason to suspect the presence of an EFNB1 gene mutation. Prenatal screening may be done by performing an ultrasound, where can be searched specifically for hypertelorism or a bifid nasal tip. However, this is quite difficult as facial involvement may not be obvious at such an early age, especially in cases with mild phenotypic presentation. The most definitive way to prove the presence of CFND is done by genetic testing, through amniocentesis and chorionic villus sampling. This however carries a greater risk of premature termination of the pregnancy.

In terms of treatment/management for those with Mulibrey nanism should have routine medical follow-ups, additionally the following can be done:

- Growth hormone treatment

- Regular pelvic exams

- Pericardiectomy

Diagnosis is based on clinical findings and can be confirmed by cytogenetic testing, when the deletion is in an average of 5 Mb (millions of base pairs). Nowadays is a common practice to run an aCHG (array chromosome hybridization genome) study on peripheral blood of the patient, in order to limit the extent of the loss of the genomic area, and the deleted genes.

Orofaciodigital syndrome type 1 is diagnosed through genetic testing. Some symptoms of Orofaciodigital syndrome type 1 are oral features such as, split tongue, benign tumors on the tongue, cleft palate, hypodontia and other dental abnormalities. Other symptoms of the face include hypertelorism and micrognathia. Bodily abnormalities such as webbed, short, joined, or abnormally curved fingers and toes are also symptoms of Orofaciodigital syndrome type 1. The most frequent symptoms are accessory oral frenulum, broad alveolar ridges, frontal bossing, high palate, hypertelorism, lobulated tongue, median cleft lip, and wide nasal bridge. Genetic screening of the OFD1 gene is used to officially diagnose a patient who has the syndrome, this is detected in 85% of individuals who are suspected to have Orofaciodigital syndrome type 1.

Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis.

Treatment of 3-M syndrome is aimed at the specific symptoms presented in each individual. With the various symptoms of this disorder being properly managed and affected individuals having normal mental development, 3-M syndrome is not a life - threatening condition and individuals are able to lead a near normal life with normal life expectancy.

Treatment may involve the coordinated efforts of many healthcare professionals, such as pediatricians, orthopedists, dentists and/or other specialists depending on the symptoms.

- Possible management options for short stature are surgical bone lengthening or growth hormone therapy.

- Orthopedic techniques and surgery may be used to treat certain skeletal abnormalities.

- Plastic surgery may also be performed on individuals to help correct certain cranio-facial anomalies.

- Individuals with dental abnormalities may undergo corrective procedures such as braces or oral surgeries.

Recent research has been focused on studying large series of cases of 3-M syndrome to allow scientists to obtain more information behind the genes involved in the development of this disorder. Knowing more about the underlying mechanism can reveal new possibilities for treatment and prevention of genetic disorders like 3-M syndrome.

- One study looks at 33 cases of 3M syndrome, 23 of these cases were identified as CUL7 mutations: 12 being homozygotes and 11 being heterozygotes. This new research shows genetic heterogeneity in 3M syndrome, in contrast to the clinical homogeneity. Additional studies are still ongoing and will lead to the understanding of this new information.

- This study provides more insight on the three genes involved in 3M syndrome and how they interact with each other in normal development. It lead to the discovery that the CUL7, OBS1, and CCDC8 form a complex that functions to maintain microtubule and genomic integrity.

While no genetic syndrome is capable of being cured, treatments are available for some symptoms. External fixators have been used for limbic and facial reconstructions.

While many cases of HPMRS are caused by mutations in the PIGV gene, there may be genetic heterogeneity in the spectrum of Mabry syndrome as a whole. PIGV is a member of the molecular pathway that synthesizes the glycosylphosphatidylinositol anchor. The loss in PIGV activity results in a reduced anchoring of alkaline phosphatase to the surface membrane and an elevated alkaline phosphatase activity in the serum.

The isochromosome i(12p) can be primarily detected in samples of skin fibroblasts, as well as in chorionic villus and amniotic fluid cell samples. Very rarely, it can also be detected in blood lymphocytes. It is also possible to detect the isochromosome in circulating lymphocytes, as well as other amniotic and placental samples. There is no strict limit as to where the isochromosome can be found. However, it is often unlikely that these samples will be tested when the blood karyotype is normal.

Using an ultrasound, Pallister-Killian may be diagnosed through observation of hypertelorism, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia, and hydramnios. Once born, a child may be diagnosed by observation of the syndrome's distinct facial features.

Orofaciodigital syndrome type 1 can be treated with reconstructive surgery or the affected parts of the body. Surgery of cleft palate, tongue nodules, additional teeth, accessory frenulae, and orthodontia for malocclusion. Routine treatment for patients with renal disease and seizures may also be necessary. Speech therapy and special education in the later development may also be used as management.

In a sample of 19 children, a 1997 study found that 3 died before the age of 3, and 2 never learned to walk. The children had various levels of delayed development with developmental quotients from 60 to 85.

Hyperphosphatasia with mental retardation syndrome, HPMRS, also known as Mabry syndrome, has been described in patients recruited on four continents world-wide. Mabry syndrome was confirmed to represent an autosomal recessive syndrome characterized by severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features that include: hypertelorism, a broad nasal bridge and a rectangular face.

Eye surgery has been documented to help those with ocular diseases, such as some forms of glaucoma.

However, long term medical management of glaucoma has not proven to be successful for patients with Weill–Marchesani syndrome. Physical therapy and orthopedic treatments are generally prescribed for problems stemming from mobility from this connective tissue disorder. However, this disorder has no cure, and generally, treatments are given to improve quality of life.