Carlos Bacino, MD, is the medical director of the cytogenetics laboratory at Baylor Genetics.

Carlos Bacino, MD, FACMG 

Characteristic clinical and radiographic findings can establish early suspicion for achondroplasia, while molecular and prenatal testing are helping clinicians confirm the diagnosis sooner.

Recognizing and Diagnosing Achondroplasia

In this episode, “Recognizing and Diagnosing Achondroplasia,” the panelists explore how achondroplasia is identified clinically and radiographically and how genetic testing can confirm the diagnosis.

The discussion begins with the characteristic phenotype seen in infants with achondroplasia. The panel highlights disproportionate shortening of the limbs, particularly rhizomelic shortening of the proximal extremities, along with macrocephaly, midface hypoplasia, and characteristic findings involving the hands and joints. For clinicians experienced in skeletal dysplasias, this combination of features can make the diagnosis highly recognizable. The panel then reviews radiographic findings that can further support the diagnosis, including characteristic changes involving the pelvis, acetabula, and proximal femur. Once achondroplasia is suspected, molecular confirmation of an FGFR3 mutation becomes an important step before treatment discussions begin.

Prenatal identification is also addressed. The experts note that achondroplasia is often not apparent on the standard 20-week anatomy scan, but third-trimester imaging may reveal shortened long bones, frontal bossing, or midface abnormalities that raise suspicion. They also discuss the increasing availability of noninvasive prenatal testing using maternal blood to detect the characteristic FGFR3 mutation once the condition is suspected. Together, these advances are helping move diagnosis earlier in the patient journey and may provide families with additional time for counseling and preparation before or shortly after birth.

The next episode, “Recognizing the Multisystem Burden of Achondroplasia,” will examine what happens after diagnosis. The panel will discuss the neurologic, respiratory, skeletal, and developmental complications that require ongoing surveillance throughout childhood.

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Achondroplasia is driven by overactive FGFR3 signaling that disrupts normal growth plate function. The panel explains how this molecular pathway affects endochondral bone growth and provides the foundation for understanding targeted treatment.

Understanding the Pathophysiology of Achondroplasia

Welcome back to another HCPLive Peer Exchange series. In this episode titled, “Understanding the Pathophysiology of Achondroplasia,” the panel reviews the molecular basis of achondroplasia and the role of fibroblast growth factor receptor 3 (FGFR3) in skeletal growth and development. The discussion begins with the identification of FGFR3 as the gene responsible for achondroplasia and its normal function in regulating chondrocyte proliferation. The panel explains that most appendicular bones and portions of the axial skeleton develop through endochondral ossification, a process that depends on carefully balanced signaling within the growth plate.

Under normal conditions, FGFR3 acts as one of several signals that restrain chondrocyte proliferation. In achondroplasia, a gain-of-function mutation causes FGFR3 signaling to become overactive, creating an excessive inhibitory effect on chondrocyte proliferation and differentiation. This disrupts normal endochondral ossification and leads to impaired longitudinal bone growth and the characteristic skeletal phenotype associated with achondroplasia. By establishing the underlying biology first, the panel provides important context for the remainder of the discussion. Understanding how excessive FGFR3 signaling affects skeletal development also helps explain why contemporary therapies seek to influence this pathway and restore a more favorable balance in growth plate signaling.

In the next episode, “Recognizing and Diagnosing Achondroplasia,” panelists will move from molecular biology to the clinical presentation of the disease. They will discuss the physical and radiographic findings that raise suspicion for achondroplasia and the role of genetic and prenatal testing in confirming the diagnosis.

Once-Weekly Navepegritide Safe and Efficacious for Achondroplasia, With Carlos Bacino, MD

 approved Ascendis Pharma’s navepegritide treatment for 

 met with Carlos Bacino, MD, medical director of the Cytogenetics Laboratory at Baylor Genetics and a lead author on the pivotal ApproaCH study, which drove the FDA’s approval under the Accelerated Approval Program. Bacino discussed the reassuring safety data coming from the trial program.

“This is a drug that has been shown to be very safe in that the side effects have been mild and not clinically significant,” Bacino told 

. “These drugs do have an effect on blood pressure, potentially decreasing it – in this particular situation, this is something that has been looked at very carefully to determine if it has caused any clinical hypotension and decreasing blood pressure. In most cases, these side effects are minimal.”

Navepegritide is a prodrug of C-type natriuretic peptide (CNP) utilizing the TransCon technology platform, which is designed to transiently link an inert carrier to a parent drug with known biology. The moiety of CNP in navepegritide is identical to the amino acid sequence 89-126 of endogenous CNP – after weekly subcutaneous administration, autocleavage of the linker occurs under physiologic pH and temperature. This provides predictable, sustained release and continuous systemic exposure to active CNP.

The FDA’s decision was based on the pivotal ApproaCH phase 2b randomized, double-blind, placebo-controlled, multicenter trial, conducted across 10 academic hospitals across 7 countries. Patients aged 2-11 years with a genetically confirmed achondroplasia diagnosis who were naïve to treatment with growth-promoting agents and height recorded ≥6 months prior to randomization were eligible for inclusion. Patients with radiographic evidence of closed growth plates, severe untreated sleep apnea, or conditions known to affect growth, among other criteria, were excluded.

Patients were randomly assigned in a 2:1 ratio to receive either subcutaneous navepegritide at 100 µg/kg/week or placebo; both drugs were administered once weekly for 52 weeks, followed by 52 weeks of follow-up. A total of 86 patients were screened and 84 were enrolled, with 57 randomized to navepegritide and 27 to placebo. Navepegritide demonstrated superiority to placebo at week 52, as children receiving it achieved a least-squares mean AGV of 5.89 versus 4.42 cm/year for those treated with placebo.

Bacino also discussed the promising potential of weekly injections as opposed to daily treatment. He mentions the likelihood of increased adherence and more direct drug effects via the TransCon platform.

“The weekly injection will allow a much more physiologic delivery of the drug and will definitely improve adherence, as it is certainly better for children, who are often reluctant to needles,” Bacino said. “It’s also better for parents who are not necessarily happy about the frequency of injections, and it’s better for the busy family to be able to handle the drug regimen.”

Editors’ Note: Bacino reports disclosures with Ascendis Pharma, BioMarin Pharmaceutical, IONIS Pharmaceuticals, and Teladoc Health.

Ascendis Pharma. FDA Approves Once-Weekly YUVIWEL (navepegritide) for Children with Achrondroplasia Aged 2 Years and Older. February 27, 2026. Accessed April 15, 2026. 

https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-once-weekly-yuviwelr-navepegritide-children

Savarirayan R, McDonnell C, Bacino CA, et al. Once-weekly Navepegritide in children with achondroplasia. JAMA Pediatrics. 2026;180(1):18. 

Bacino highlights the recently approved treatment’s safety data and emphasizes the likelihood of increased adherence due to longer intervals between administration.

Carlos Bacino, MD, FACMG

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