Normative growth charts for individuals with Costello syndrome

Self Cite

103

111

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues;however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are

Section: Gastroenterologic Findingsmentioning

confidence: 99%

Costello syndrome: Clinical phenotype, genotype, and management guidelines

Gripp

Morse

Axelrad

et al. 2019

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103

111

“…Weight loss in the first days after birth is due the resolution of edema and the severe swallowing and sucking problems [Gripp et al, 2012], already present in prenatal period, as evidenced by polyhydramnios. The severe failure to thrive has a low point at around age 12 months [Sammon et al, ]. Similar other RASopathies, delayed bone age is common.…”

Section: Introductionmentioning

confidence: 99%

Response to long‐term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data

Tamburrino

Gibertoni

Rossi

et al. 2015

RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

“…Growth issues are common to many genetic conditions other than achondroplasia, including Costello syndrome. Medical experts have used this collaborative clinical research model at Costello Syndrome Support Group meetings to develop normative growth charts [Sammon et al, ].…”

Section: Discussionmentioning

confidence: 99%

Academia, advocacy, and industry: A collaborative method for clinical research advancement

Vanzo

Lortz²,

Calhoun

et al. 2014

Professionals who work in academia, advocacy, and industry often carry out mutually exclusive activities related to research and clinical care. However, there are several examples of collaboration among such professionals that ultimately allows for improved scientific and clinical understanding. This commentary recounts our particular experience (a collaboration between geneticists at the Universities of Minnesota and Utah, the 4p-Support Group, and Lineagen, Inc) and reviews other similar projects. We formally propose this collaborative method as a conduit for future clinical research programs. Specifically, we encourage academicians, directors of family/advocacy/support groups, and members of industry to establish partnerships and document their experiences. The medical community as a whole will benefit from such partnerships and, specifically, families will teach us lessons that could never be learned in a laboratory or textbook.