In the photo: Janet Legare, MD, (left), and Peggy Modaff, MS, CGC, (right)
Bone or skeletal dysplasia is an umbrella term covering approximately 700 congenital disorders of bone growth. Most are extremely rare, and more than half manifest as disproportionate short stature, known as dwarfism. One of these disorders, achondroplasia, is the most common form of dwarfism. It is the cause of approximately 90% of dwarfism in people of all races and ethnic groups. It is caused by a mutation in the FGFR3 gene and occurs in about one in 25,000 births. In 1981, one year after he joined the genetics department at the then University of Wisconsin School of Medicine, Richard M. Pauli, MD, PhD, a pioneer in clinical genetics and research who specialized in bone dysplasia, established the Midwest Regional Bone Dysplasia Clinic to treat patients with achondroplasia and other skeletal dysplasia conditions.
That same clinic, much expanded, continues today with the addition of the Skeletal Dysplasia Multidisciplinary Clinic under the direction of Janet Legare, MD, professor, in the Divisions of Genetics and Metabolism and Developmental Pediatrics and Rehabilitation Medicine. She also holds an affiliate appointment in the Department of Neurological Surgery. Legare works with Peggy Modaff, MS, CGC, distinguished clinical genetic counselor in the Division of Genetics and Metabolism, and a team of dedicated physicians in several specialties, including orthopedic surgery, neurosurgery, sleep medicine, and ENT/otolaryngology. Together they collaborate in addressing the health concerns of both children and adult patients with skeletal dysplasia such as achondroplasia and other conditions, offering seven varying clinics per month.
The program is considered among the best in the country, on par with the clinics in Houston, Johns Hopkins, Nemours Children’s Health in Delaware, and others. Recent data show that patients traveled from 24 states seeking the expertise and care of these clinicians. Legare is licensed in nine states, allowing her to offer telemedicine to patients in states far from Wisconsin.
Legare came to the Department of Pediatrics in 2014 with long experience as a pediatrician working with children with complex diagnoses and serving children with special needs. She held affiliate appointments with the University of Colorado and Regis University. Soon after arriving in Madison, she became the director of the Midwest Regional Bone Dysplasia Clinic in 2015. From nearly the moment of her arrival, Legare began three years of work in the clinic with Richard Pauli to learn everything she could from him before he retired.
“It was like a three-year apprenticeship,” Legare explained. “I was overlapping him in the work every day he was in the office, learning everything about the clinic, about skeletal dysplasia, and about the patients, trying to take in everything he knew.”
Legare noted that Pauli had worked with Ralph S. Lachman, MD, a physician, researcher, and radiologist at Cedars-Sinai and UCLA (now retired), who definitively described achondroplasia and other skeletal dysplasia in the text, Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasia, still in use in its fifth edition. Thus, Pauli, himself a pioneer in his field of genetics, worked with a clinician–researcher responsible for building the foundations to understanding skeletal dysplasia. Pauli’s Midwest Regional Bone Dysplasia Clinic arose from an extraordinary concentration of expertise. Legare was acutely aware of the need to absorb knowledge and effectively take on the clinic’s enormous responsibilities to serve its patients.
Achondroplasia arises from a mutation in the FGFR3 gene, which causes a malfunction of that gene’s receptor, interfering with its normal processes at growth plates. The result is anomalous cartilage and decreased bone growth throughout the skeleton.
Achondroplasia is associated with short stature and skeletal characteristics, such as short limbs, large head with prominent forehead, small facial features, a narrow spinal column, shortened fingers and toes, and limited range of motion at the elbows. People affected reach an adult height of 42 to 56 inches, and they are typically of normal intelligence. As patients age — and their life expectancy today is 60–65 years — their skeletal abnormalities can impair movement, cause pain, and lead to other conditions such obstructive sleep apnea.
The achondroplasia mutation can be passed on through one parent; however, it is important to note that in about 80% of cases, achondroplasia arises from a spontaneous new mutation of the FGFR3 gene. That is, people of average height who do not carry the mutation themselves can have a child with achondroplasia through a new mutation. There are approximately 13,000 people with achondroplasia and 30,000 people with dwarfism in the U.S. today.
The range of deleterious physical effects of achondroplasia requires the expertise of many specialists to address them. Legare’s clinic team includes those experts. The Skeletal Dysplasia Multidisciplinary Clinic comprises specialists from many fields, including audiology, ENT (ear, nose, and throat), genetics, neurosurgery, nursing, ophthalmology, orthopedics, pulmonology, and sleep medicine. The orthopedic surgeon can address arm and leg malformations, hip issues, and bowing of the legs, for example. The neurosurgeon addresses hydrocephalus; spinal curvature, instability, and compression; as well as spinal narrowing (stenosis) throughout the entire spine.
James (Andy) Stadler, MD, MAS, is an associate professor in the Department of Neurological Surgery with a joint appointment in the Department of Pediatrics. He joined the clinic’s team of specialists eight years ago. “It has been great to help extend the reach and impact of this program. My clinical subspecialty focus is complex congenital and syndromic spine surgery, and patients with skeletal dysplasia often have significant spinal concerns,” Stadler explained. “We are lucky to have great partnerships across specialties, but more importantly, partnerships with patients and their families. Those connections allow us to learn from each other and continuously improve in a field where patients often otherwise would not have teams or resources with the depth of experience needed for complex problems like these.”
With six to seven separate clinics per week, the clinic serves 30-45 patients per month, nearly 500 patients annually. Its newest multidisciplinary clinic allows patients — who often drive in from other states — to see several specialists on one day per month. Neurosurgery, ENT, orthopedics, and genetics are available in one clinic.
Peggy Modaff, the genetic counselor and overall coordinator, has been an integral part of the clinic since 1996. She is responsible for gathering crucial medical information, keeping things organized, keeping things moving. “She is without a doubt the rock of the clinic,” Legare said, “and she knows everything.”
Modaff stepped into a position with the clinic fortuitously. While she was helping with some clinic research just after she graduated, the genetics counselor working in the clinic took another job. Modaff stepped into the role.
“I was really drawn to the model of care that the clinic provided,” Modaff explained. “The amount of trust the families put into the care providers, and that it allowed for a long-term relationship between the providers and the family, immediately hooked my interest. I thought it was something I would really enjoy.”
Modaff explained that people come to the clinic from all over the country. Sometimes they have other specialists who are more local to them, but they notice that this clinic provides something extra.
“Families have commented that we are almost like the quarterback. For their care, we are looking at the whole entire child or the whole adult, and we are making sure all their health care needs are being addressed at one time,” Modaff said, “rather than going to an orthopedist who is just looking at your legs. We see and address the whole picture, the whole person.”
One of the advantages of the clinic is that the team has experience with hundreds of children with skeletal dysplasia. “We know when something is outside of the range of what we would expect in a particular diagnosis,” Modaff explained.
As Modaff did, Legare lauded the teamwork of the staff. “The most salient characteristic of the clinic is that everything we do is a collaboration,” Legare explained. “Because we are known as one of the best programs of this kind in the country, we also work to be a bona fide program for skeletal dysplasia. This means not only offering a large clinic with multiple specialists, but also participating in active research and providing access to clinical trials for our patients.”
The staff lets patients who come for clinical care know that they may participate in clinical trials if they want that, and they explain what a clinical trial can and cannot offer.
Legare explained that the clinic serves people throughout the lifespan, and that their patients range in age from newborn to 70 years. “We don’t send them elsewhere when they reach 18,” Legare said. “We are in this for the long term. We have and nurture those longitudinal relationships. It is one of the many things I am passionate about, one of the many things I love about this work with this patient population.”
Legare noted the importance of the organization, Little People of America, a non-profit organization that provides support, resources, and information for these people and their families.