August 2026

Title:  Neurodevelopmental and neurological features in children with hypochondroplasia

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Abstract

Aim

To assess neurodevelopmental and neurological features, including neuroimaging abnormalities, in children with molecularly confirmed hypochondroplasia.

Method

A retrospective cohort study of children with molecularly confirmed hypochondroplasia seen at Evelina London Children's Hospital skeletal dysplasia service was performed. Data collected included referral characteristics, neuroimaging findings, special educational needs, and diagnosed neurodevelopmental disorders. Statistical comparisons with UK population prevalence were performed using χ2 testing for educational outcomes and exact binomial testing for neurodevelopmental disorders, with Bonferroni-adjusted p-values reported for multiple comparisons.

Results

Forty-four children (24 females and 20 males; median age 9 years 10 months [interquartile range 6 years 7 months–15 years 7 months]) with molecularly confirmed hypochondroplasia were included. Twenty-five had received brain imaging with hippocampal malrotation (HIMAL) identified in 23 (92%). Among school-aged children, 71% required special educational support and 29% had formal education, health, and care plans (EHCPs), statistically higher than both UK population prevalence and previously reported hypochondroplasia prevalence. Formally diagnosed neurodevelopment disorders affected 20.5% of the cohort. Specific learning disorders remained significantly more common than UK population prevalence estimates after Bonferroni correction, with higher observed autism and attention-deficit/hyperactivity disorder rates also identified.

Title:  Diagnosis of hypochondroplasia: international Delphi consensus recommendations 

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Abstract

Hypochondroplasia is a skeletal dysplasia caused by pathogenic variants in FGFR3 and characterized by disproportionate short stature and relative macrocephaly. Diagnostic uncertainty remains common, particularly in early childhood and in individuals with mild or atypical presentations, leading to delayed diagnosis, inconsistent management, and challenges in counselling and care planning. Individuals can be affected by medical complications and psychosocial consequences and have unmet needs for multidisciplinary care. To address these unmet needs, an international, multidisciplinary panel of experts and patient representatives convened to develop consensus-based diagnostic recommendations using a modified two-stage Delphi approach, with a predefined consensus threshold of 70% of respondents rating statements ≥70 (on a scale of 0 to 100). The panel integrated clinical, anthropometric, radiographic, neuroimaging and genetic criteria to define diagnostic categories that can be applied across diverse health-care settings globally. Major and minor diagnostic criteria are proposed, alongside guidance on the appropriate use of molecular testing, radiographic evaluation and brain magnetic resonance imaging. These recommendations provide a practical framework to help standardize timely and accurate diagnosis of hypochondroplasia in clinical practice and research.

Title: International guideline on genetic testing of children with short stature

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Abstract

Short stature may be caused by a multitude of conditions, including genetic and non-genetic factors such as hypochondroplasia. Over the last decade, advances in genetic sequencing technologies have revolutionized our understanding of the underlying physiology of growth and greatly increased our ability to identify genetic etiologies of short stature. This current guideline provides a general overview of the approach to evaluating a child with short stature, followed by recommendations that identify key factors in the medical and family history, physical examination, radiographic, and laboratory work-up which enhance the likelihood of identifying a genetic etiology. An algorithm is proposed for the genetic workup of individuals with short stature based on their clinical presentation. Additionally, the benefits and risks of genetic testing are discussed, along with references to relevant medical resources and research publications.

Title: Pathways to Facilitate Early Recognition and Diagnosis of Hypochondroplasia

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Abstract

Hypochondroplasia (HCH) is a disproportionate short-statured skeletal dysplasia condition caused by gain-of-function pathogenic variants in the fibroblast growth receptor 3 gene (FGFR3). Although HCH typically becomes clinically apparent after the first year of life, when height discrepancy compared with the general population becomes more pronounced, diagnosis is often delayed by several years. Early recognition of hypochondroplasia is challenging due to wide phenotypic variability and subtle clinical and radiographic features, which can lead to delayed or missed diagnosis. Additionally, the heterogeneity of variants and restrictive testing criteria can further contribute to diagnostic delays. Early diagnosis may facilitate timely clinical management and psychosocial support, but currently, there are no standardized diagnostic criteria for hypochondroplasia, nor are the diagnostic pathways well described in the medical resources and research publications.

Title: Parental Perception of Quality of Life and Impact of Short Stature in Children with Hypochondroplasia and Other Genetic Causes of Short Stature

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Abstract

Short stature, often seen in conditions such as hypochondroplasia and other genetic factors, can lead to physical limitations and socioemotional effects that impact both a child's and parents' quality of life (QoL). This study aims to explore the influence of these genetic causes, including ACAN, NPR2 mutations, and RASopathy, on QoL, utilizing various medical resources and relevant research publications.

Title: Living With Hypochondroplasia: A Qualitative Exploration of Children's and Caregivers' Experiences, Challenges, and Unmet Needs

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Abstract

Hypochondroplasia (HCH) is a rare genetic skeletal dysplasia characterized by short stature, disproportionate limbs, and associated complications such as learning differences. Currently, there are no approved medical resources to address HCH-related short stature, which can significantly impact quality of life. This study aimed to explore diagnostic processes, care pathways, daily life impacts, and the unmet needs of individuals affected by hypochondroplasia, contributing to the body of research publications in this field.

Title: The Head Circumference Height Index (HCH-I) to Quantify Relative Macrocephaly and Aid Identification of Hypochondroplasia in Children

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Abstract

Hypochondroplasia (HCH) is a rare skeletal dysplasia resulting from pathogenic variants in the FGFR3 gene. In our research publications, we hypothesized that the relative disproportion between head circumference and height in HCH could be diagnostically informative. Therefore, we developed a simple index of head-stature disproportion to assist pediatricians in diagnosing hypochondroplasia effectively.

Title: Growth Reference Charts for Children with Hypochondroplasia

Link: Growth reference charts for children with hypochondroplasia Cheung et al. 2024

Abstract

Hypochondroplasia (HCH) is a rare skeletal dysplasia characterized by mild short stature. There is a lack of comprehensive growth reference charts specifically for this population, which highlights the need for better medical resources. To address this gap, anthropometric data were collected to create height, weight, and head circumference (HC) growth reference charts for children diagnosed with HCH. Mixed longitudinal anthropometric data, alongside genetic analysis results, were gathered from 14 specialized skeletal dysplasia centers across Europe. Growth charts were developed using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were compiled from 188 children (79 female) aged 0-18 years with a diagnosis of HCH. Among the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). This data was utilized to generate growth references for height, weight, and HC, depicted as charts featuring seven centiles ranging from the 2nd to the 98th, for ages 0-4 and 0-16 years. The development of HCH-specific growth charts is crucial in the clinical care of these children. These charts assist in identifying potential comorbidities that may impact growth and development and serve as a vital benchmark for future research publications and interventional studies.

Title: Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

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Abstract

Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.