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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.
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)
Treatment is usually supportive treatment, that is, treatment to reduce any symptoms rather than to cure the condition.
- Enucleation of the odontogenic cysts can help, but new lesions, infections and jaw deformity are usually a result.
- The severity of the basal-cell carcinoma determines the prognosis for most patients. BCCs rarely cause gross disfigurement, disability or death .
- Genetic counseling
Treatment is usually confined to such surgical intervention as may be necessary to help the child to develop e.g. jaw distraction/bone grafts, ocular dermoid debulking (see below), repairing cleft palate/lip, repairing heart malformations or spinal surgery. Some patients with Goldenhar syndrome will require assistance as they grow by means of hearing aids or glasses.
Stem cell grafting (womb tissue grafting) has been successfully used to "reprogram" eye dermoids, effectively halting the regrowth of eye dermoids.
These tissues that grow on the eye are "mis-programmed" cells (sometimes tooth or nail cells instead of eye cells).
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.
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.
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
NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal-cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmar and plantar pits.
One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.
Café au lait spots can be removed with lasers. Results are variable as the spots are often not completely removed or can come back after treatment. Often, a test spot is treated first to help predict the likelihood of treatment success.
Screening for melanoma in FAMMM kindreds should begin at age 10 with a baseline total body skin examination including scalp, eyes, oral mucosa, genital area, and nail, as family members may develop melanoma in their early teens.
At Mayo Clinic, FAMMM patients with a confirmed mutation and family history of pancreatic cancer are offered screening with either high-resolution pancreatic protocol CT, MRI, or endoscopic ultrasound starting at age 50 or 10 years younger than the earliest family member with pancreas cancer. They are counseled on the lack of evidence-based data to support screening, and on the limitations of our current technology to detect a lesion at a stage amenable to therapy.
The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to suffer from the syndrome. Since the disorder is very rare, its incidence rate is difficult to estimate, but is less than 1 in 10,000.
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
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.
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.
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.
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.
Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the "popliteal web syndrome" and, more inclusively, the "facio-genito-popliteal syndrome". The term PPS was coined by Gorlin "et al.." in 1968 on the basis of the most unusual anomaly, the popliteal pterygium (a web behind the knee).
The cause of Goldenhar syndrome is largely unknown. However, it is thought to be multifactorial, although there may be a genetic component, which would account for certain familial patterns. It has been suggested that there is a branchial arch development issue late in the first trimester.
An increase in Goldenhar syndrome in the children of Gulf War veterans has been suggested, but the difference was shown to be statistically insignificant.
McKusick–Kaufman syndrome is a genetic condition associated with MKKS.
The condition is named for Dr. Robert L. Kaufman and Victor McKusick. It is sometimes known by the abbreviation MKS. In infancy it can be difficult to distinguish between MKS and the related Bardet–Biedl syndrome, as the more severe symptoms of the latter condition rarely materialise before adulthood.
Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.
Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.
Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.
FACES syndrome is a syndrome of unique facial features, anorexia, cachexia, eye and skin anomalies.
It is a rare disease and estimated to occur in less than 1 in 1 million people.
The long-term prognosis of Costeff syndrome is unknown, though it appears to have no effect on life expectancy at least up to the fourth decade of life. However, as mentioned previously, movement problems can often be severe enough to confine individuals to a wheelchair at an early age, and both visual acuity and spasticity tend to worsen over time.
Café au lait spots can arise from diverse and unrelated causes:
- Having six or more café au lait spots greater than 5 mm in diameter before puberty, or greater than 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I, but other features are required to diagnose NF-1.
- Familial multiple café au lait spots have been observed without NF-1 diagnosis.
- They can be caused by vitiligo in the rare McCune–Albright syndrome.
- Legius syndrome
- Tuberous sclerosis
- Fanconi anemia
- Idiopathic
- Ataxia-telangiectasia
- Basal cell nevus syndrome
- Benign congenital skin lesion
- Bloom syndrome
- Chédiak–Higashi syndrome
- Congenital naevus
- Gaucher disease
- Hunter syndrome
- Jaffe–Campanacci syndrome
- Maffucci syndrome
- Multiple mucosal neuroma syndrome
- Noonan syndrome
- Pulmonary Stenosis
- Silver–Russell syndrome
- Watson syndrome
- Wiskott–Aldrich syndrome
Orofaciodigital syndrome 1 (OFD1), also called Papillon-League and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.
This includes Chediak-Higashi syndrome and Elejalde syndrome (neuroectodermal melanolysosomal disease).