There is currently no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases there may be cosmetic issues. Other abnormalities (neurological, structural, Hirschsprung disease) associated with the syndrome are treated symptomatically.

Many professionals that are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists, physical therapists and rheumatologists.

Since the symptoms caused by this disease are present at birth, there is no “cure.” The best cure that scientists are researching is awareness and genetic testing to determine risk factors and increase knowledgeable family planning. Prevention is the only option at this point in time for a cure.

Treatment for the disease itself is nonexistent, but there are options for most of the symptoms. For example, one suffering from hearing loss would be given hearing aids, and those with Hirschsprung’s disorder can be treated with a colostomy.

If the Hirschsprung's disease is treated in time, ABCD sufferers live otherwise healthy lives. If it is not found soon enough, death often occurs in infancy. For those suffering hearing loss, it is generally regressive and the damage to hearing increases over time. Digestive problems from the colostomy and reattachment may exist, but most cases can be treated with laxatives. The only other debilitating symptom is hearing loss, which is usually degenerative and can only be treated with surgery or hearing aids.

Since Usher syndrome results from the loss of a gene, gene therapy that adds the proper protein back ("gene replacement") may alleviate it, provided the added protein becomes functional. Recent studies of mouse models have shown one form of the disease—that associated with a mutation in myosin VIIa—can be alleviated by replacing the mutant gene using a lentivirus. However, some of the mutated genes associated with Usher syndrome encode very large proteins—most notably, the "USH2A" and "GPR98" proteins, which have roughly 6000 amino-acid residues. Gene replacement therapy for such large proteins may be difficult.

The overall incidence is ~1/42,000 to 1/50,000 people. Types I and II are the most common types of the syndrome, whereas types III and IV are rare. Type 4 is also known as Waardenburg‐Shah syndrome (association of Waardenburg syndrome with Hirschsprung disease).

Type 4 is rare with only 48 cases reported up to 2002.

About 1 in 30 students in schools for the deaf have Waardenburg syndrome. All races and sexes are affected equally. The highly variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence.

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.

There is no cure for Alström syndrome; however, there are treatment aims to reduce the symptoms and prevent further complications. Some of these treatment aims include:

- Corrective lenses: tinted lenses that help with the sensitivity from bright lights. The patients may have to adapt to reading in Braille, use adaptive equipment, mobility aids, and adaptive computing skills.

- Education: patients with Alström syndrome suffering from intellectual disabilities must have access to education. They must be able to receive free and appropriate education. Some Alström syndrome patients are educated in normal classrooms. Other patients have to take special education classes or attend to specialized schools that are prepared to teach children with disabilities. Staff members from schools have to consult with patient's parents or caregivers in order to design an education plan based on the child's needs. In addition, the school may document the progress of the child in order to confirm that the child's needs are being met.

- Hearing aids: the battery-operated devices are available in three styles: behind the ear, in the ear, and inside the ear canal. Behind the ear aims for mild-to-profound hearing loss. In the ear aims for mild to severe hearing loss. Lastly, the canal device is aimed for mild to moderately severe hearing loss. Patients that have severe hearing loss may benefit from a cochlear implant.

- Diet: an appropriate and healthy diet is necessary for individuals with Alström syndrome because it could potentially decreases chances of obesity or diabetes.

- Occupational therapy: the therapist helps the child learn skills to help him or her perform basic daily tasks like eating, getting dressed, and communicating with others.

- Physical Activity: exercising reduces chances of being obese and helping control blood sugar levels.

- Dialysis: helps restore filtering function. With hemodialysis, a patient's blood circulates into an external filter and clean. The filtered blood is then returned into the body. With peritoneal dialysis, fluid containing dextrose is introduced into the abdomen by a tube. The solution then absorbs the wastes into the body and is then removed.

- Transplantation: patients that endure a kidney failure may undergo a kidney transplantation.

- Surgery: if the patient endures severe scoliosis or kyphosis, surgery may be required.

Opitz G/BBB Syndrome is a rare genetic condition caused by one of two major types of mutations: MID1 mutation on the short (p) arm of the X chromosome or a mutation of the 22q11.2 gene on the 22nd chromosome. Since it is a genetic disease, it is an inherited condition. However, there is an extremely wide variability in how the disease presents itself.

In terms of prevention, several researchers strongly suggest prenatal testing for at-risk pregnancies if a MID1 mutation has been identified in a family member. Doctors can perform a fetal sex test through chromosome analysis and then screen the DNA for any mutations causing the disease. Knowing that a child may be born with Opitz G/BBB syndrome could help physicians prepare for the child’s needs and the family prepare emotionally. Furthermore, genetic counseling for young adults that are affected, are carriers or are at risk of carrying is strongly suggested, as well (Meroni, Opitz G/BBB syndrome, 2012). Current research suggests that the cause is genetic and no known environmental risk factors have been documented. The only education for prevention suggested is genetic testing for at-risk young adults when a mutation is found or suspected in a family member.

Overall, the estimated prevalence of Stickler syndrome is about 1 in 10,000 people. Stickler syndrome affects 1 in 7,500 to 9,000 newborns.

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.

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Alstrom syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Meckel-Gruber syndrome and some forms of retinal degeneration.

Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. In severe cases, respiratory and neurological complications often lead to early death.

The main treatment is symptomatic, since the underlying genetic defect cannot be corrected as of 2015. Symptomatic treatment is surgical.

A publication in the "Journal of Medical Genetics" in 1987 by Dr. I. Young and D. Madders of Leicester Royal Infirmary in the United Kingdom described the then-unknown condition when presenting "a stillborn male infant with pre-maxillary agenesis, bilateral microphthalmos, alobar holoprosencephaly, hydrocephalus, ventricular and atrial septal defects, small penis, bilateral cryptorchidism, and bilateral upper limb postaxial polydactyly." Both doctors noted no use of drugs, alcohol or cigarettes by the mother, and the baby was delivered normally after forty-one weeks of gestation. It was the first child of the parents, who were not related and went on to have another child successfully however this child was a stillbirth. There was severe overlapping of the bones of the skull and a cleft lip in addition to the bilateral polydactyly. Of the organs, Young and Madders noted missing parts of the tricuspid valve and other small cardiac defects, as well as the holoprosencephaly. Both doctors consulted various medical databases and, after discounting Meckel syndrome due to a lack of renal abnormalities, concluded that this was a hitherto unclassified condition. After later classification, it was later named for the two doctors, though at the time of publication it was termed 'pseudotrisomy 13' due to similarities with the condition Trisomy 13. Another case in 1989 with similar symptoms was also published as an example of 'pseudotrisomy 13', and there was no evidence of an extra chromosome, further suggesting that Trisomy 13 was a separate condition.

The RASopathies are developmental syndromes caused by germline mutations (or in rare cases by somatic mosaicism) in genes that alter the Ras subfamily and mitogen-activated protein kinases that control signal transduction, including:

- Capillary malformation-AV malformation syndrome

- Autoimmune lymphoproliferative syndrome

- Cardiofaciocutaneous syndrome

- Hereditary gingival fibromatosis type 1

- Neurofibromatosis type 1

- Noonan syndrome

- Costello syndrome, Noonan-like

- Legius syndrome, Noonan-like

- Noonan syndrome with multiple lentigines, formerly called LEOPARD syndrome, Noonan-like

Usher syndrome, also known as Hallgren syndrome, Usher-Hallgren syndrome, retinitis pigmentosa-dysacusis syndrome, or dystrophia retinae dysacusis syndrome, is an extremely rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing loss and visual impairment. It is a leading cause of deafblindness and is at present incurable.

Usher syndrome is classed into three subtypes according to onset and severity of symptoms. All three subtypes are caused by mutations in genes involved in the function of the inner ear and retina. These mutations are inherited in an autosomal recessive pattern.

Heart-hand syndrome type 3 is very rare and has been described only in three members of a Spanish family. It is also known as Heart-hand syndrome, Spanish type.

The prognosis of this condition is generally considered good with the appropriate treatment. Management of Legius syndrome is done via the following:

- Physical therapy

- Speech therapy

- Pharmacologic therapy(e.g.Methylphenidate AHHD)

Albinism–deafness syndrome (also known as "Woolf syndrome" and "Ziprkowski–Margolis syndrome") is a condition characterized by congenital neural deafness and a severe or extreme piebald-like phenotype with extensive areas of hypopigmentation.

A locus at Xq26.3-q27.I has been suggested.

It has been suggested that it is a form of Waardenburg syndrome type II.

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genotypical root cause of these widely varying, phenotypically-observed disorders. Orofaciodigital syndrome has been found to be a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney disease and polycystic liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.

Heart-hand syndrome type 2 is also known as Berk–Tabatznik syndrome. Berk–Tabatznik syndrome is a condition with an unknown cause that shows symptoms of short stature, congenital optic atrophy and brachytelephalangy. This condition is extremely rare with only two cases being found.

Sporadic reports of the case continued, with 'pseudotrisomy 13' becoming a common term due to the similar pathology to Trisomy 13. However, there was a growing belief that unlike Trisomy 13, Young–Madders syndrome was not caused by a duplicated chromosome, and in fact the cause lay in some other fault with chromosome thirteen. In 1991 a publication in the "Journal of Medical Genetics" by a group of eight doctors, based on a five-patient case-study, argued that Trisomy 13 and Young–Madders syndrome were two distinct conditions and renamed the disorder to avoid confusion. Their case studies, when viewed together, suggested a recessive genetic cause, based on the repeated instances of holoprosencephaly polydactyly in the aforementioned five cases, which led to the suspicion of an anomaly in chromosome thirteen's genetic coding. Chromosome thirteen spans about 114 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA in cells. Problems with this chromosome account for several conditions including nonsyndromic deafness, Waardenburg syndrome and Wilson's disease.

The majority of the cases discussed in the journal were still born, with death occurring between twenty-six and thirty-four weeks of gestation. All suffered with the features of Young–Madders syndrome, with varying cardiac problems and facial deformities. The distinctive bilateral polydactyly and overlapping of the cranial skull plates were present, though some had no deformities in their internal organs while others had lung deformities alone. Hydrocephalus and holoprosencephaly were present in all. The publication noted the work of Young and Madders and suggested that the cases were linked, and also identified two cases from a year previously - 1986 - which had until then been diagnosed as Smith-Lemli-Opitz syndrome. The doctors discounted several other similar genetic conditions including Varadi-Papp syndrome and Grote syndrome, and discarded the term 'pseudotrisomy 13 syndrome' as misleading, preferring 'holoprosencephaly-polydactyly syndrome'.

Griscelli syndrome type 2 (also known as "partial albinism with immunodeficiency") is a rare autosomal recessive syndrome characterized by variable pigmentary dilution, hair with silvery metallic sheen, frequent pyogenic infections, neutropenia, and thrombocytopenia.