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 HCH is challenging because of wide phenotypic variability and subtle clinical and radiographic features, leading to delayed or missed diagnosis. Furthermore, wide variant heterogeneity and restrictive testing criteria can contribute to diagnostic delays. Early diagnosis may facilitate timely clinical management and psychosocial support. However, no standardized diagnostic criteria for HCH currently exist, nor are diagnostic pathways well described in the literature. In October 2024, 14 experts across multiple specialties completed an online survey on current clinical practices for diagnosing HCH. A subset convened in person to discuss strategies to optimize clinical diagnostic pathways, which were subsequently refined by the collective group. Age-specific diagnostic opportunities were identified. Prenatally, sonographic features of HCH may be detectable from approximately 20 weeks' gestation. Postnatally, features suggestive of HCH include a sustained fall in length/height centiles over the first 2 years of life, relative macrocephaly, neonatal seizures, and specific radiographic and neuroimaging findings. Between ages 2-3 years, a characteristic growth pattern including limb shortening and body disproportion may become evident. Neurocognitive involvement including neurodevelopmental challenges may become apparent. HCH should be considered in the differential diagnosis of idiopathic or isolated short stature. Genetic testing panels that include FGFR3 and evaluation of short-statured parents can support diagnosis. Early diagnosis of HCH is achievable when age-specific key clinical and radiologic features are recognized and supported by molecular testing using appropriate diagnostic platforms. This work represents an important first step towards developing consensus-based diagnostic guidelines for HCH.

To characterize the metacarpophalangeal pattern profile (MCPP) of healthy children and adolescents from São Paulo, Brazil, and to establish percentile curves by chronological age (CA), bone age (BA), and sex using the LMS method. Additionally, to compare these findings with previous population-based data and to apply the derived standards to patients with skeletal dysplasias. Left hand and wrist radiographs were obtained from healthy individuals and age-matched patients with confirmed skeletal dysplasias. Tubular bone lengths were compared across CA and BA, against prior normative studies, and with dysplastic cohorts using Student's t-test. Patient Z-scores were calculated from LMS parameters generated from the healthy population. We analyzed 974 radiographs from healthy subjects and 83 from patients (18 hypochondroplasia, 27 achondroplasia, 14 osteogenesis imperfecta, 24 Turner syndrome). In healthy participants, hand bone lengths correlated significantly with CA and BA. Compared with international reference data, differences in mean metacarpal and phalangeal lengths were noted. Patients with achondroplasia and hypochondroplasia exhibited markedly reduced Z-scores relative to controls, whereas those with Turner syndrome showed reductions of up to 1.8 SD in the fourth metacarpal. Patients with osteogenesis imperfecta demonstrated no significant deviations. This study established MCPP reference percentiles for Brazilian children and adolescents using the LMS method. Bone measurements showed consistent associations with CA and BA. Although differences were observed relative to international cohorts, the generated standards effectively discriminated dysplastic phenotypes, particularly achondroplasia and hypochondroplasia, supporting the use of MCPP analysis as an adjunct tool for evaluating short stature and suspected skeletal dysplasias.

Achondroplasia (ACH), the most common skeletal dysplasia, arises from gain-of-function variants in the fibroblast growth factor receptor 3 gene. Children with ACH experience lifelong medical, functional and psychosocial challenges requiring coordinated and anticipatory care. Although international guidance exists, the UK lacks national clinical care recommendations specific to its healthcare systems. To develop UK-specific, multidisciplinary clinical recommendations for the care of children and young people (CYP) with ACH. The UK Achondroplasia Network developed guidance in stages: stakeholder mapping of the care pathway, integration of contemporary literature with clinical expertise to draft age-specific guidance and Delphi statements, and a modified Delphi process with 25 multidisciplinary experts. The Delphi process involved two voting rounds and an in-person meeting, with consensus defined as ≥80% agreement. In the first Delphi round, all 20 statements achieved consensus; nine achieved 100% agreement. To strengthen consensus, after meeting in person, 17 statements were refined (four were divided into two statements), one created and one removed, resulting in 24 statements for Round 2; all achieved consensus, with 21 reaching 100% agreement. The guidance outlines age-specific monitoring and referral from infancy to adolescence. Recommendations address medical management of complications, psychosocial support, educational planning and transfer to adult care. These are the first UK-specific multidisciplinary recommendations for the care of CYP with ACH. Aligned with international best practices and tailored to UK healthcare systems, they support anticipatory care, promote independence and enhance health and psychosocial outcomes. The guidelines offer a foundation for service planning, standardisation and equitable care.

Hypochondroplasia (HCH) is a rare skeletal dysplasia caused by pathogenic variants in the FGFR3 gene. We hypothesized that the relative disproportion between head circumference and height in HCH might be diagnostically informative and generated a simple index of head-stature disproportion to help pediatricians diagnose HCH. The Head Circumference Height Index (HCH-I), based on formal statistical principles, is defined as height Z-score - 1/2 head circumference Z-score, with the Z-scores based here on the UK90 growth reference. An HCH-I below the cut-off of -2 indicates substantial head-height disproportion. We validated the index by comparing children diagnosed with HCH (n = 364), using data from the recent European HCH growth charts, to children from the Cambridge Infant Growth Study (CIGS) (n = 4620). The mean (SD) HCH-I was -3.0 (1.2) in the HCH cohort, compared to -0.2 (0.9) in the CIGS cohort. An HCH-I below -2 correctly identified 78% of children with HCH, while only 2.4% of CIGS children fell below the cut-off. An HCH-I below -2 identifies children with head-height disproportion who may have HCH or another genetic disorder. The index is deliberately simple to calculate and should prove useful in clinical practice. Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and relative macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; a lack of widening or a narrowing of the lumbar interpedicular distances with shortening of the pedicle length and posterior scalloping of the vertebral bodies; short, broad femoral neck; and squared, shortened ilia. The skeletal features are similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., foramen magnum stenosis, spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia, but intellectual disability and epilepsy may be more prevalent. Children usually present as toddlers or at early school age with decreased growth velocity leading to short stature and limb disproportion. Other features also become more prominent over time. Infants may present with temporal lobe seizures. The diagnosis of hypochondroplasia is established in a proband with characteristic clinical and radiographic features. Identification of a heterozygous FGFR3 pathogenic variant known to be associated with hypochondroplasia can confirm the diagnosis and help distinguish hypochondroplasia from achondroplasia and other related skeletal dysplasias in individuals with overlapping phenotypes. Treatment of manifestations: Management of short stature in hypochondroplasia is influenced by parental expectations and concerns; one approach is to address these concerns rather than trying to treat the child. Foramen magnum stenosis, thoracolumbar kyphosis, genu varum, and spinal stenosis are management by orthopedists and neurosurgeons using similar strategies employed in achondroplasia. Seizures are treated in the standard manner. Developmental and educational support as needed. Connecting families with local resources and support is important. Surveillance: The following should be performed at routine well-child visits: measurement and assessment of height, weight, and head circumference using hypochondroplasia-standardized growth curves; assessment for signs and symptoms of spinal cord compression, sleep apnea, thoracolumbar kyphosis, and leg bowing; development assessment and monitoring of all developmental domains including speech and language; audiology evaluation if speech and/or hearing concerns arise. Evaluation of social adjustment at well-child visits and then annually, most important during the grade-school years. Pregnancy management: Vaginal deliveries are possible, although for each pregnancy, pelvic outlet capacity should be assessed in relation to fetal head size; epidural or spinal anesthetic can be used, but a consultation with an anesthesiologist prior to delivery is recommended to assess the spinal anatomy; spinal stenosis may be aggravated during pregnancy. Hypochondroplasia is inherited in an autosomal dominant manner. The majority of individuals with hypochondroplasia have parents of average stature and have hypochondroplasia as the result of a de novo pathogenic variant. An individual with hypochondroplasia who has a reproductive partner of average stature has a 50% chance of having a child with hypochondroplasia. When the proband and the proband's reproductive partner have the same or different skeletal dysplasias, genetic counseling is more complex. In general, if both members of a couple have a dominantly inherited skeletal dysplasia, each child has a 25% chance of having average stature, a 25% chance of having the same skeletal dysplasia as the father, a 25% chance of having the same skeletal dysplasia as the mother, and a 25% chance of inheriting a pathogenic variant from both parents and being at risk for a potentially poor pregnancy outcome. It is not possible to provide information about prognosis for all at-risk offspring. If one parent has hypochondroplasia and the other parent is of average stature, has hypochondroplasia, or has another dominantly inherited skeletal dysplasia, prenatal and preimplantation genetic testing are possible if the causative pathogenic variant(s) have been identified in the affected parent(s).

We report a case of multiple suture craniosynostosis in a patient with hypochondroplasia. The patient presented with short stature marked by a relatively long trunk and short extremities. The clinical and radiological findings were suggestive of hypochondroplasia. Additionally, craniosynostosis was identified during the evaluation, which is an unusual finding in hypochondroplasia. To further investigate, exome sequencing was performed, revealing previously reported pathogenic heterozygous variants in FGFR3 and ERF genes. Exome sequencing not only enhances the accuracy of diagnosing individual cases of genetic skeletal disorders but also contributes to the collective knowledge base, advancing future research in the field.