Publications

Most Comprehensive Publication on Costello Syndrome:

“Costello syndrome: Clinical phenotype, genotype, and management guidelines” (Gripp et al, 2019, PMID: 31222966)

General:

“HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy” (Estep et al, 2006, PMID: 16372351)

• Talks about correlations between certain mutations and common characteristics of Costello syndrome. Has a nice table showing how many individuals with Costello syndrome had each characteristic.

“Medically actionable comorbities in adults with Costello syndrome” (Shikany et al, 2020, PMID: 31680412)

• Researchers surveyed 20 adults with Costello syndrome to see what people with Costello syndrome and their families should anticipate, health-wise, as the child becomes an adult.

 

Vision:

“Ophthalmic manifestations in Costello syndrome caused by Ras pathway dysregulation during development” (Shankar et al, 2021, PMID: 34612139)

• Discusses the most common ophthalmic manifestations across fifty-six molecularly diagnosed CS individuals.

“Retinal dystrophy in two boys with Costello syndrome due to the HRAS p.Gly13Cys mutation” (Pierpoint et al, 2017, PMID: 28337834)

• Case report of two boys with Costello syndrome who have retinal dystrophy and other vision issues. Paper also includes a general overview of vision issues that can occur in patients with Costello syndrome.

 

Pulmonary:

“Obstructive sleep apnea in Costello syndrome” (Marca et al, 2006, PMID: 16419102)

• Evaluates sleep quality of individuals with Costello syndrome; results suggest that people with Costello syndrome have a high prevalence of obstructive sleep-related respiratory disorders.

 

“Respiratory system involvement in Costello syndrome” (Gomez-Ospina et al, 2016, PMID: 27102959)

• Comprehensive description of the full spectrum of respiratory symptoms in patients with Costello syndrome, as well as how common it is.

 

Cardiovascular:

“Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome” (Lin et al, 2011, PMID: 21344638)

• Discusses what different cardiovascular abnormalities (including congenital heart defects, hypertrophic cardiomyopathy, and atrial tachycardia, among others) were present in the 146 individuals studied with Costello syndrome, and how many people had each type of abnormality.

 

Gastrointestinal:

“Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure” (Leoni et al, 2016, PMID: 26778095)

• Study which shows that individuals with Costello syndrome need more energy for their resting state than other people do, which the researchers speculate might be one of the reasons individuals with Costello syndrome typically have failure to thrive.
• Not publicly available

 

Genito-Urinary:

“Perinatal Features of the RASopathies: Noonan Syndrome, Cardiofaciocutaneous Syndrome and Costello Syndrome” (Myers et al, 2014, PMID: 25250515)

• Not publicly available

 

Musculoskeletal:

“Costello Syndrome: Orthopaedic Manifestations and Functional Health” (Yassir et al, 2003, PMID: 12499952)

• Study which evaluated 16 individuals with Costello syndrome for orthopedic issues. Researchers identified delayed walking, inability to run, tight heel cords, and a variety of other challenges.
• Not publicly available

 

“Orthopedic manifestations and implications for individuals with Costello syndrome” (Detweiler, 2013, PMID: 23813656)

• Study which further defines orthopedic manifestations that affect people with Costello syndrome. Researchers studied 43 participants and completed hip and/or spinal imaging assessments in 23 of them, which showed 10 different manifestations seen in the majority of participants.
• Not publicly available

 

“Craniofacial and dental development in Costello syndrome.” (Goodwin et al, 2014, PMID: 24668879)

“RASopathies – what they reveal about RAS/MAPK signaling in skeletal muscle development” (Rauenn, Tidyman, 2024, PMID: 38847227)

 

Neurological:

“High incidence of progressive postnatal cerebellar enlargement in Costello syndrome: brain overgrowth associated with HRAS mutations as the likely cause of structural brain and spinal cord abnormalities” (Gripp et al,2010, PMID: 20425820)

• Review article which talks about the neurological differences that individuals with Costello syndrome can have, and shows that individuals with Costello syndrome have disproportionate brain growth throughout their life.

 

“Costello syndrome: Analysis of the posterior cranial fossa in children with posterior fossa crowding” (Calandrelli et al., 2015, PMID: 26246091)

• Study which looks at changes in the brainstem and cerebellum to better understand the mechanism of cerebellar herniation in children with Costello syndrome and crowding of the small space in the skull near the brainstem and cerebellum called the posterior fossa.
• Publicly available

 

Neurocognition and Development:

“Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome” (Axelrad et al., 2009, PMID: 19919001)

• Researchers report on standardized IQ and adaptive functioning in 18 individuals with Costello syndrome, as well as longitudinal development for those who had previous testing.
• Publicly available

 

“Neurocognitive, adaptive, and behavioral functioning of individuals with Costello syndrome: a review.” (Axlerad et al, 2011, PMID: 21495179)

• Not publicly available

 

“Age-related differences in prevalence of autism spectrum disorder symptoms in children and adolescents with Costello syndrome.” (Schwartz et al, 2017, PMID: 28374929)

• Publicly available

 

“Age and ASD symptoms in Costello syndrome.” (Young O et al, 2018, PMID: 29575620)

• Rebuttal to above article
• Publicly available

 

Growth and Puberty:

“Normative growth charts for individuals with Costello syndrome” (Sammon et al., 2012, PMID: 22887473)

• Publicly available

 

“RASopathies Are Associated With Delayed Puberty; Are They Associated With Precocious Puberty Too?” (van der Kaay et al., 2016, PMID: 27940666)

• Case report which documents 2 males with Costello syndrome who had precocious puberty, suggesting that Costello syndrome may be associated with both delayed and precious puberty.
• Publicly available

 

“Impact of Costello syndrome on growth patterns” (Leoni et al., 2020, PMID: 32845069)

• Researchers gathered 10 years of data on patients with Costello syndrome to analyze which factors had an impact on their growth patterns. They found that CS patients all achieved harmonic growth (meaning weight and height, while lower than typical, were in appropriate ranges in relation to each other).
• Not publicly available

 

Skin and Hair:

“Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development” (Siegel, Mann, Krol & Rauen, 2012, PMID: 22098123)

• Researchers aimed to identify specific cutaneous phenotypes of individuals with Costello syndrome. They identified cutaneous papillomas as a major finding in individuals with Costello syndrome.
• Publicly available

 

“Cutaneous manifestations in Costello and cardiofaciocutaneous syndrome: report of 18 cases and literature review” (Morice-Picard et al., 2013, PMID: 24283439)

• Researchers aimed to describe the spectrum of skin findings in Costello syndrome and cardiofaciocutaneous syndrome and highlight skin findings that are specific to these two diseases.
• Not publicly available

 

Hematology/Oncology:

“Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes” (Kratz et al., 2011, PMID: 21500339)

• Researchers evaluated 268 individuals with Costello syndrome and found that 19 had rhabdomyosarcoma, 4 had bladder cancer, and 5 had neuroblastoma. By age 20, they found that the cumulative risk for cancer was approximately 15% for CS.
• Publicly available

 

“Tumor predisposition in Costello syndrome” (Gripp, 2005, PMID: 16010679)

• Review article discussing the various cancer risks for individuals with Costello syndrome and suggested screening and management protocols.
• Not publicly available

 

Adulthood:

“The adult phenotype in Costello syndrome” (White et al., 2005, PMID: 15940703)

• Paper which describes what adults with Costello syndrome are like and what health challenges they face.
• Not publicly available

 

“Living with Costello syndrome: quality of life issues in older individuals” (Hopkins et al., 2010, PMID: 20034064)

• Researchers surveyed older individuals with Costello syndrome, as well as their caregivers, to better understand their quality of life.
• Not publicly available