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)

There is no cure for the disorder itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. In progress and recently concluded medical studies on NF-1 can be found by searching the official website of the National Institutes of Health.

At the 2005 American Society of Human Genetics meeting, Francis Collins gave a presentation about a treatment he devised for children affected by Progeria. He discussed how farnesyltransferase inhibitor (FTI) affects H-Ras. After his presentation, members of the Costello Syndrome Family Network discussed the possibility of FTIs helping children with Costello syndrome. Mark Kieran, who presented at the 1st International Costello Syndrome Research Symposium in 2007, agreed that FTIs might help children with Costello syndrome. He discussed with Costello advocates what he had learned in establishing and running the Progeria clinical trial with an FTI, to help them consider next steps.

Another medication that affects H-Ras is Lovastatin, which is planned as a treatment for neurofibromatosis type I. When this was reported in mainstream news, the Costello Syndrome Professional Advisory Board was asked about its use in Costello Syndrome. Research into the effects of Lovastatin was linked with Alcino Silva, who presented his findings at the 2007 symposium. Silva also believed that the medication he was studying could help children with Costello syndrome with cognition.

A third medication that might help children with Costello syndrome is a MEK inhibitor that helps inhibit the pathway closer to the cell nucleus.

Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.

Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.

Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis

It is suggested that, once diagnosed, individuals be routinely followed by a cardiologist, endocrinologist, dermatologist, and other appropriate specialties as symptoms present.

It is recommended that those with the syndrome who are capable of having children seek genetic counseling before deciding to have children. As the syndrome presents frequently as a "forme fruste" (incomplete, or unusual form) variant, an examination of all family members must be undertaken. As an autosomal dominant trait there is a fifty percent chance with each child that they will also be born with the syndrome. Although fully penetrant, since the syndrome has variable expressivity, one generation may have a mild expression of the syndrome, while the next may be profoundly affected.

Once a decision to have children is made, and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy.

Other management is routine care as symptoms present:

1. For those with endocrine issues (low levels of thyrotopin [a pituitary hormone responsible for regulating thyroid hormones], follicle stimulating hormone) drug therapy is recommended.

2. For those who are disturbed by the appearance of lentigines, cryosurgery may be beneficial. Due to the large number of lentigines this may prove time consuming. An alternative treatment with tretinoin or hydroquinone creams may help.

3. Drug therapies for those with cardiac abnormalities, as those abnormalities become severe enough to warrant the use of these therapies. ECG's are mandatory prior to any surgical interventions, due to possible arrythmia.

In itself, NSML is not a life-threatening diagnosis, most people diagnosed with the condition live normal lives. Obstructive cardiomyopathy and other pathologic findings involving the cardiovascular system may be a cause of death in those whose cardiac deformities are profound.

Children with NF-1 can experience social problems, attention problems, social anxiety, depression, withdrawal, thought problems, somatic complaints, learning disabilities and aggressive behavior. Treatments include psychotherapy, antidepressants and cognitive behavioral therapy.

Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008. Although the G12V mutation is rare among children with Costello syndrome, and the G12V mouse does not appear to develop tumors as expected, information about the mouse model's heart may be transferrable to humans.

Italian and Japanese researchers published their development of a Costello zebrafish in late 2008, also with the G12V mutation. The advent of animal models may accelerate identification of treatment options.

Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1), it is caused by mutations in the SPRED1 gene, it is also known as Neurofibromatosis Type 1-like syndrome (NFLS). The condition is a RASopathy, developmental syndromes due to germline mutations in genes

A 2007 study followed 112 individuals for a mean of 12 years (mean age 25.3, range 12–71). No patient died during follow-up, but several required medical interventions. The mean final heights were 167 and 153 cm for men and women, respectively, which is approximately 2 standard deviations below normal.

Gingival fibromatosis with hypertrichosis is a cutaneous condition characterized by dark terminal hairs on the peripheral face, central back, and extremities. It is a RASopathy.

Noonan syndrome (NS) is a relatively common autosomal dominant congenital disorder and is named after Jacqueline Noonan, a pediatric cardiologist. It is referred to as the male version of Turner's syndrome; however, the genetic causes of Noonan syndrome and Turner syndrome are distinct and both males and females are affected. The principal features include congenital heart defect (typicall pulmonary valve stenosis with dysplastic pulmonary valve also atrial septal defect and hypertrophic cardiomyopathy), short stature, learning problems, pectus excavatum, impaired blood clotting, and a characteristic configuration of facial features including a webbed neck and a flat nose bridge. NS is a RASopathy, and is one of several disorders that are caused by a disruption of RAS-MAPK signaling pathway.

It is believed that between approximately 1 in 1,000 and 1 in 2,500 children worldwide are born with NS. It is one of the most common genetic syndromes associated with congenital heart disease, similar in frequency to Down syndrome. However, the range and severity of features can vary greatly in patients with NS. Therefore, the syndrome is not always identified at an early age.

Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis. It is a RASopathy.

It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.