Costello syndrome community mourns New Zealand pediatrician


Jack Costello remembered for his support of families affected by the condition

When New Zealand pediatrician Jack Costello, MD, died in December 2010, he left a disorder bearing his name and hundreds of families and researchers grateful for his astute clinical observations and the research and treatment advances they made possible.

Dr. Costello first identified a relationship between 2 children's intellectual disabilities, poor growth, similar facial appearance, and wart-like growths called nasal papillomata in 1971 [Costello, 1971]. In 1977, Dr. Costello published more detailed observations in the New Zealand Medical Journal [Costello, 1977]. Nearly 20 years later, when the disorder was well known as Costello syndrome (CS), he wrote about those 2 patients in a follow-up that added a list of adult features including high blood pressure, breast fibroadenoma, and skeletal complications including scoliosis and tight Achilles tendons [Costello, 1996].

Researcher Susan White, MD, a medical geneticist at Australia's Genetic Health Services Victoria and member of the International Costello Syndrome Support Group's (ICSSG) professional advisory committee, praises the reports for their unusually “finely drawn, accurate details.”

“It may seem that a case report of 2 children is not a big deal, but it was an instigating event,” she says. Dr. Costello's reports enabled definition of a syndrome and facilitated families' improved understanding their children's condition, research aimed at treatment, and clinicians' ability to anticipate complications and provide better care for the roughly 300 children worldwide with the disorder, White explains.

Dr. Costello's case report set off a chain of subsequent reports of other affected children and prompted clinical and molecular research into CS, culminating in the 2005 discovery of HRAS gene mutations that cause the disorder, Dr. White says. CS is now known to be 1 of a group of related disorders, including Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, and neurofibromatosis 1 (NF1), caused by abnormal functioning of the Ras-mitogen-activated protein kinase (RAS/MapK) pathway. Collectively, these conditions are now known as RASopathies. The careful phenotyping by Dr. Costello and others gave rise to recognition of these conditions as distinct syndromes, Dr. White says.

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In 1971, Dr. Costello identified a relationship between 2 children's intellectual disabilities, poor growth, similar facial appearance, and wart-like growths.

Knowledge of their differences informs care. CS syndrome patients, for example, are prone to malignant tumors and should be screened for them, while tumor predisposition is not a feature of CFC, she adds.

A Boon for Families

Dr. Costello's initial observations of CS have transformed life for some families affected by the disorder.

Costello Syndrome Family Network (CSFN) President Tammy Moore was grateful to just have a name for her daughter's medical problems when she was diagnosed shortly before her second birthday. Getting the diagnosis ended a grueling medical odyssey and “gave us hope and direction,” Moore recalls. “Because Dr. Costello was there, we were able to learn how to take care of our daughter Kelsi, who is now 17.”

Moore quickly became active in CSFN and was chair of its first conference, held in 1999. The conference drew families from across the U.S. and all over the world. “It was great to see other children like ours, because my daughter was the only person with Costello in all of Alabama,” she says.

In 2009, CFN members and families in the the CFC, Noonan, and NF1 family advocacy organizations held a joint reception with researchers attending their own conference on the diseases of the Ras MAPK pathway in Berkeley, Calif. That Berkeley reception with the investigators put “a human face” to CS and allowed researchers and families from across the globe to make connections, Moore says. In Kelsi's case, one was medically important. Networking at the reception helped Moore find a pediatric surgeon for Kelsi's kyphoscoliosis.

Encouraging Families

Dr. Costello embraced parents' efforts to advocate for their children, says past CSFN President Lisa Schoyer, whose son Quin died of CS-related cancer when he was 6. Her email correspondence with Dr. Costello “reinforced for us parents our role as informers and sharers of any information that came forward,” she says. According to Schoyer, Dr. Costello's encouragement in part led to creation of a CSFN listserv through which parents trade information, help each other analyze the information they gather, form questions for physicians, and identify clinical patterns that have become the subject of studies.

Support from Dr. Costello during regular telephone conversations spurred the United Kingdom's Colin Stone in 1995 to start an informal CS support and advocacy group with just 2 families. Officially begun as ICSSG in 1996, the organization now has 178 families who exchange information on its listserv.

“In the early days, doctors said these kids wouldn't achieve much, but Dr. Costello said that was not the case,” says Stone, who is director of ICSSG and whose daughter Helaina, age 16, has CS and dances competitively. “He said 'Always ask questions. Never give up on anything,' ” recalls Stone, who has made these words the motto for his organization's website.

These words also inspired Stone to launch a new organization, RASopathy Network UK (http://ras-pathway-syn-dromes.com), in 2010 and to create a web site for parents to communicate (http://news.costellokids.com). Meanwhile, Schoyer has established a North American counterpart called RA Sopathies Network USA. These organizations have been linking with CFN and organizations that advocate for children CFC,NF1,andNS.

The four RASopathy groups' family meetings will overlap and support the second research symposium, “International Meeting on Genetic Syndromes of the Ras/MAPK Pathway: Finding Our Way Back to the Bedside,” on July 29–31. Schoyer says, who will assist Bruce Gelb, MD, Professor of Pediatrics, Cardiology, and Genetics and Genomic Sciences at Mount Sinai School of Medicine, and Amy Roberts, MD, Assistant Professor of Pediatrics at Harvard Medical School, in chairing a forum on basic science and clinical issues surrounding RASopathies.

Schoyer looks forward to the meeting and the research advances that may come from connections made there. “The parent-researcher relationship is so symbiotic,” she says.

FOR MORE INFO

See the May issue of AJMG Part C. for more on RASopathy diseases.

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