Many of the congenital malformations found with Malpuech syndrome can be corrected surgically. These include cleft lip and palate, omphalocele, urogenital and craniofacial abnormalities, skeletal deformities such as a caudal appendage or scoliosis, and hernias of the umbillicus. The primary area of concern for these procedures applied to a neonate with congenital disorders including Malpuech syndrome regards the logistics of anesthesia. Methods like tracheal intubation for management of the airway during general anesthesia can be hampered by the even smaller, or maldeveloped mouth of the infant. For regional anesthesia, methods like spinal blocking are more difficult where scoliosis is present. In a 2010 report by Kiernan et al., a four-year-old girl with Malpuech syndrome was being prepared for an unrelated tonsillectomy and adenoidectomy. While undergoing intubation, insertion of a laryngoscope, needed to identify the airway for the placement of the endotracheal tube, was made troublesome by the presence of micrognathia attributed to the syndrome. After replacement with a laryngoscope of adjusted size, intubation proceeded normally. Successful general anesthesia followed.

A rare follow-up of a male with Malpuech syndrome was presented by Priolo et al. (2007). Born at term from an uneventful pregnancy and delivery, the infant underwent a surgical repair of a cleft lip and palate. No problems were reported with the procedure. A heart abnormality, atrial septal defect, was also apparent but required no intervention. At age three years, mental retardation, hyperactivity and obsessive compulsive disorder were diagnosed; hearing impairment was diagnosed at age six, managed with the use of hearing aids. Over the course of the decade that followed, a number of psychiatric evaluations were performed. At age 14, he exhibited a fear of physical contact; at age 15, he experienced a severe psychotic episode, characterized by agitation and a loss of sociosexual inhibition. This array of symptoms were treated pharmocologically (with prescription medications). He maintained a low level of mental deficiency by age 17, with moments of compulsive echolalia.

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).

There is currently no specified treatment for individuals suffering from otodental syndrome. Considering that there are many possible genetic and phenotypic associations with the condition, treatment is provided based on each individual circumstance. It is recommended that those affected seek ear, nose & throat specialists, dental health specialists, and facial oral health specialists immediately; in order to determine potential treatment options.

Common treatment methods given are:

- Dental treatment/management – which can be complex, interdisciplinary and requires a regular follow up. Tooth extraction(s)and if needed, medications may be administered for pain, anxiety, and anti-inflammation. The affected individual is usually placed on a strict and preventative dental regiment in order to maintain appropriate oral hygiene and health.

- Endodontic treatment – individuals consult with an endodontist to analyze the individuals dental pulp. Typically endodontic treatment proves to be difficult due to duplicated pulp canals within the affected teeth. There may be a need for multiple extractions as well. Dental prosthesis and/or dental implants may be necessary for individuals that lack proper oral function, appearance, and comfort.

- Orthodontic treatment – given the predicament of the size and location of the affected oral area, molars and canines, orthodontic treatment is generally required in order treat any problems associated with the individuals bite pattern and tooth appearance.

- Hearing aids – in some cases affected individuals will suffer from hearing imparities and it may be necessary for hearing aid use.

The functional prognosis is mostly good with those that suffer from otodental syndrome. Appropriate dental treatment, hearing aids, and visitation to necessary specialists are recommended. Quality of life may be affected by psychological and functional aspects. It is also recommended that genetic counseling be given to families that have or may have this condition.

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.

Surgery is typically used to correct structural heart defects and syndactyly. Propanolol or beta-adrenergic blockers are often prescribed as well as insertion of a pacemaker to maintain proper heart rhythm. With the characterization of Timothy syndrome mutations indicating that they cause defects in calcium currents, it has been suggested that calcium channel blockers may be effective as a therapeutic agent.

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.

Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, speech and hearing therapy may benefit some patients. Infants with abnormal breathing patterns should be monitored.

The syndrome is associated with progressive worsening for kidneys, the liver and the eyes and thus require regular monitoring.

There is no known cure for microcephaly. Treatment is symptomatic and supportive.

Management often includes the use of beta blockers such as propranolol or if not tolerated calcium channel blockers or ACE inhibitors.

Since angiotensin II receptor antagonists (ARBs) also reduce TGF-β, these drugs have been tested in a small sample of young, severely affected people with Marfan syndrome. In some, the growth of the aorta was reduced. However, a recent study published in NEJM demonstrated similar cardiac outcomes between the ARB, losartan, and the more established beta blocker therapy, atenolol.

There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and is now similar to that of the average person. Regular checkups by a cardiologist are needed to monitor the health of the heart valves and the aorta. The syndrome is treated by addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation. The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate, and minimizing blood pressure.

There is currently no cure for Costeff syndrome. Treatment is supportive, and thus focuses on management of the symptoms. The resulting visual impairment, spasticity, and movement disorders are treated in the same way as similar cases occurring in the general population.

Currently there are no open research studies for otodental syndrome. Due to the rarity of this disease, current research is very limited.

The most recent research has involved case studies of the affected individuals and/or families, all of which show the specific phenotypic symptoms of otodental syndrome. Investigations on the effects of FGF3 and FADD have also been performed. These studies have shown successes in supporting previous studies that mutations to FGF3 and neighboring genes may cause the associated phenotypic abnormalities. According to recent studies involving zebrafish embryos, there is also support in that the FADD gene contributed to ocular coloboma symptoms as well.

Future research studies are required in order to better grasp the specific relationship between the gene involved and its effect on various tissues and organs such as teeth, eyes, and ear. Little is known and there is still much to be determined.

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

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.

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.

While no cure for MDS is available yet, many complications associated with this condition can be treated, and a great deal can be done to support or compensate for functional disabilities. Because of the diversity of the symptoms, it can be necessary to see a number of different specialists and undergo various examinations, including:

- Developmental evaluation

- Cardiologists evaluation

- Otolaryngology

- Treatment of seizures

- Urologic evaluation

- Genetic counseling-balanced chromosomal translocation should be excluded in a parents with an affected child are planning another pregnancy, so parents with affected children should visit a genetic counselor.

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.

Malpuech facial clefting syndrome, also called Malpuech syndrome or Gypsy type facial clefting syndrome, is a rare congenital syndrome. It is characterized by facial clefting (any type of cleft in the bones and tissues of the face, including a cleft lip and palate), a appendage (a "human tail"), growth deficiency, intellectual and developmental disability, and abnormalities of the renal system (kidneys) and the male genitalia. Abnormalities of the heart, and other skeletal malformations may also be present. The syndrome was initially described by Guilliaume Malpuech and associates in 1983. It is thought to be genetically related to Juberg-Hayward syndrome. Malpuech syndrome has also been considered as part of a spectrum of congenital genetic disorders associated with similar facial, urogenital and skeletal anomalies. Termed "3MC syndrome", this proposed spectrum includes Malpuech, Michels and Mingarelli-Carnevale (OSA) syndromes. Mutations in the "COLLEC11" and "MASP1" genes are believed to be a cause of these syndromes. The incidence of Malpuech syndrome is unknown. The pattern of inheritance is autosomal recessive, which means a defective (mutated) gene associated with the syndrome is located on an autosome, and the syndrome occurs when two copies of this defective gene are inherited.

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.

Treatment of Wiskott–Aldrich syndrome is currently based on correcting symptoms. Aspirin and other nonsteroidal anti-inflammatory drugs should be avoided, since these may interfere with platelet function. A protective helmet can protect children from bleeding into the brain which could result from head injuries. For severely low platelet counts, patients may require platelet transfusions or removal of the spleen. For patients with frequent infections, intravenous immunoglobulins (IVIG) can be given to boost the immune system. Anemia from bleeding may require iron supplementation or blood transfusion.

As Wiskott–Aldrich syndrome is primarily a disorder of the blood-forming tissues, a hematopoietic stem cell transplant, accomplished through a umbilical cord blood or bone marrow transplant offers the only current hope of cure. This may be recommended for patients with HLA-identical donors, matched sibling donors, or even in cases of incomplete matches if the patient is age 5 or under.

Studies of correcting Wiskott–Aldrich syndrome with gene therapy using a lentivirus have begun.

Proof-of-principle for successful hematopoietic stem cell gene therapy has been provided for patients with Wiskott–Aldrich syndrome.

Currently, many investigators continue to develop optimized gene therapy vectors. In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that three children with Wiskott–Aldrich syndrome showed significant improvement 20–30 months after being treated with a genetically modified lentivirus. In April 2015 results from a follow-up British and French trial where six children with Wiskott–Aldrich syndrome were treated with gene therapy were described as promising. Median follow-up time was 27 months.

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

Most individuals with this condition do not survive beyond childhood. Individuals with MDS usually die in infancy and therefore do not live to the age where they can reproduce and transmit MDS to their offspring.

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period. Fryns (1987) reviewed the syndrome.

Goldenhar syndrome (also known as oculo-auriculo-vertebral (OAV) syndrome) is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip, and mandible. It is associated with anomalous development of the first branchial arch and second branchial arch. Common clinical manifestations include limbal dermoids, preauricular skin tags, and strabismus.

The term is sometimes used interchangeably with hemifacial microsomia, although this definition is usually reserved for cases without internal organ and vertebrae disruption.

It affects between 1/3,500 and 1/26,000 live births, with a male:female ratio of 3:2.

Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder. Fraser syndrome is named for the geneticist George R. Fraser, who first described the syndrome in 1962.