Costello Syndrome

Rare congenital disorder with multiple anomalies including: characteristic dysmorphic craniofacial features, musculoskeletal abnormalities, neurocognitive delay, and high prevalence of cancer. Germline mutations in H-Ras protein can cause Costello syndrome. Costello syndrome shows early phenotypic overlap with other disorders that involve MAP KINASE SIGNALING SYSTEM (e.g., NOONAN SYNDROME and cardiofaciocutaneous syndrome).

Also Known As:

Networked: 160 relevant articles (9 outcomes, 9 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hyperlipoproteinemia Type I (Lipoprotein Lipase Deficiency, Familial)
2.	Pancreatitis
3.	Inborn Genetic Diseases (Disease, Hereditary)
4.	Hypothyroidism
5.	Cryptorchidism (Undescended Testes)

Experts

1.	Gripp, Karen W: 13 articles (01/2018 - 07/2004)
2.	Sol-Church, Katia: 7 articles (05/2017 - 08/2006)
3.	Stabley, Deborah L: 7 articles (05/2017 - 08/2006)
4.	Rauen, Katherine A: 5 articles (01/2022 - 01/2006)
5.	Hsieh, Andrew: 5 articles (08/2021 - 05/2017)
6.	Arca, Marcello: 5 articles (01/2021 - 01/2018)
7.	Hinek, Aleksander: 5 articles (08/2012 - 01/2004)
8.	D'Erasmo, Laura: 4 articles (01/2021 - 01/2018)
9.	Witztum, Joseph L: 4 articles (09/2018 - 05/2017)
10.	Lin, Angela E: 4 articles (01/2018 - 02/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Costello Syndrome:

1.	Triglycerides (Triacylglycerol)IBA 01/01/2023 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. " 04/01/2022 - "Patients with the ultra-rare familial chylomicronemia syndrome (FCS) subtype completely lack lipolytic capacity and respond minimally to traditional triglyceride-lowering therapies. " 02/01/2023 - "Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by high triglyceride levels, significant disease burden, and negative impacts on health-related quality of life. " 10/01/2022 - "Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder, resulting in elevated triglycerides (TGs), abdominal pain and pancreatitis. " 09/01/2022 - "Familial chylomicronemia syndrome (FCS) is a rare and severe genetic disorder, characterized by marked elevation of plasma triglycerides, often diagnosed in infancy. "
2.	ChylomicronsIBA 03/30/2023 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations related to chylomicron metabolism. " 03/28/2023 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in genes involved in chylomicron metabolism. " 01/01/2020 - "Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder of lipid metabolism characterised by high levels of triglycerides (TGs) due to failure of chylomicron clearance. " 01/01/2022 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease, prevalence 1:200,000 - 1:1,000,000, and is characterized by fasting chylomicrons and very high triglycerides > 880 mg/dl. " 01/01/2020 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of chylomicron metabolism causing severe elevation of triglyceride (TG) levels (>10 mmol L-1 ). "
3.	Proteins (Proteins, Gene)FDA Link 10/01/2021 - "Dysregulated ECM remodeling proteins lead to aberrant osteogenesis of Costello syndrome iPSCs." 05/15/2011 - "Subsequently, additional syndromes with some overlapping physical manifestations such as Noonan syndrome, Costello syndrome, and cardiofaciocutaneous (CFC) syndrome were also shown to be due in many cases to mutations in genes encoding for proteins interacting with the Ras/MAPK pathway. " 07/01/2020 - "NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. " 08/01/2012 - "Here we demonstrate a loss of C4S, as well as a reduction in C4ST-1 mRNA and protein expression, in primary fibroblasts from Costello syndrome patients. " 03/15/2008 - "Almost all Costello syndrome mutations affect one of the glycine residues in position 12 or 13 of the protein product. "
4.	Growth Hormone (Somatotropin)IBA 01/26/2016 - "The possibility of growth hormone (GH) treatment can be considered in cases of documented GH deficiency in patients with Costello syndrome, but only under close oncologic and cardiologic supervision." 08/30/2004 - "We report on three patients with Costello syndrome and isolated growth hormone (GH) deficiency treated with biosynthetic GH. " 08/30/2004 - "Growth hormone deficiency in Costello syndrome." 06/01/2003 - "Is growth hormone treatment beneficial or harmful in Costello syndrome?" 01/01/2001 - "Growth hormone deficiency in Costello syndrome: a possible explanation for the short stature."
5.	Lipoproteins (Lipoprotein)IBA 01/01/2018 - "Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. " 11/01/2018 - "Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. " 01/01/2022 - "The accumulation of triglyceride-rich lipoproteins (TRLs) in plasma in patients with familial chylomicronaemia syndrome (FCS) or severe hypertriglyceridemia is associated with an increased risk of potentially life-threatening pancreatitis. " 11/01/2017 - "The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. " 12/01/2022 - "Familial chylomicronemia syndrome (FCS) caused by mutations of lipoprotein lipase (LPL) gene and other triglyceride-rich lipoprotein genes related with catabolism is an autosomal recessive rare disease. "
6.	EnzymesIBA 03/01/2000 - "This was further supported by the fact that exposure to chondroitinase ABC, an enzyme capable of chondroitin sulfate degradation, restored normal production of elastic fibers by fibroblasts from patients with Costello syndrome. " 05/06/2016 - "Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. " 01/01/2019 - "It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. "
7.	Diacylglycerol O-AcyltransferaseIBA 08/08/2019 - "Diacylglycerol O-acyltransferase 1 (DGAT1) inhibitor Pradigastat (1) was shown to be effective at decreasing postprandial triglyceride levels in a patient population with familial chylomicronemia syndrome (FCS). "
8.	Human Growth Hormone (Saizen)FDA LinkGeneric 01/26/2016 - "We present a patient with Costello syndrome who has been successfully treated with recombinant human growth hormone (rhGH) for almost 4 years. "
9.	Isotretinoin (Accutane)FDA LinkGeneric 01/01/2015 - "We present this case as a successful treatment option by using oral isotretinoin for the treatment of acanthosis nigricans in Costello syndrome patients. " 01/01/2015 - "Costello syndrome with severe nodulocystic acne: unexpected significant improvement of acanthosis nigricans after oral isotretinoin treatment."
10.	DiglyceridesIBA 12/01/2017 - "1. Pradigastat is a potent and specific diacylglycerol acyltransferase-1 (DGAT1) inhibitor effective in lowering postprandial triglycerides (TG) in healthy human subjects and fasting TG in familial chylomicronemia syndrome (FCS) patients. "

Therapies and Procedures

1.	Therapeutics 02/01/2013 - "These promising results need further research to confirm the relevance of OS and the efficacy of PAR therapy in Costello syndrome." 08/30/2004 - "We review the pathophysiology of Costello syndrome and highlight the recent recommendations of tumor screening and cardiac surveillance in this population, of particular relevance to those receiving GH therapy." 09/01/2020 - "Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. " 01/26/2016 - "Recombinant growth hormone therapy in a girl with Costello syndrome: a 4-year observation." 12/01/2014 - "Growth hormone replacement therapy in Costello syndrome."
2.	Airway Management 12/01/2015 - "The airway management and cardiac abnormalities are the major concerns of an anaesthesiologist in Costello syndrome. "
3.	Ventriculoperitoneal Shunt 12/01/2015 - "We report the anaesthetic management of ventriculo-peritoneal shunt replacement for hydrocephaly in an 18-month-old child with Costello syndrome. "
4.	Centric Relation 09/01/2023 - "The clinical case of a patient with Costello syndrome is presented to illustrate essential concepts in diagnosis and treatment of complex cases, including (1) Global Diagnosis of anterior esthetic relationships, (2) occlusal analysis with diagnostic casts verified in centric relation, (3) comprehensive restoration previewed with a diagnostic wax-up and removable acrylic resin overlay, (4) adhesive monobody composite resin onlays that preserve tooth structure, and (5) programmed occlusion, quantified with digital occlusal analysis, to ensure stability and comfort. "
5.	Tonsillectomy 03/01/2003 - "The authors present a 2-year old child with Costello syndrome who required anaesthesia for direct laryngoscopy, rigid bronchoscopy, bilateral pressure equalization tubes and tonsillectomy. "