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.

Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive skeletal dysplasia caused by biallelic loss-of-function variants in FLNB, characterized by disproportionate short stature, progressive vertebral fusion, scoliosis, and carpal (typically capitate–hamate) synostosis, classically without rib anomalies. We performed a systematic literature search of PubMed/MEDLINE and Scopus, supplemented by citation searching, following the PRISMA 2020 statement, to identify all reports providing original, molecularly confirmed FLNB-related SCT patient data. Eleven eligible publications, spanning Taiwanese, Argentinian, Pakistani, Italian, German and Indian cohorts, were included in a qualitative synthesis together with a novel case. The novel patient, an adopted child of Indian origin, presented with severe disproportionate short stature, multisegmental vertebral fusion and posterior arch clefts extending from the cervical to the sacral spine, coccygeal dysgenesis, capitate–hamate fusion, and global developmental delay; targeted exome sequencing identified a novel homozygous frameshift FLNB variant. Integration of this case with the reviewed literature confirms disproportionate short stature, contiguous vertebral fusion, and carpal synostosis as near-universal core features, while tarsal fusion, hearing loss, and facial dysmorphism are variably present. The extent and multisegmental pattern of axial involvement in our patient appear more severe than in most previously reported cases, broadening the recognized phenotypic spectrum of FLNB-related SCT and reinforcing the need for structured, multidisciplinary long-term follow-up.

Hajdu–Cheney syndrome (HCS) is a rare genetic skeletal disorder caused by truncating variants of NOTCH2, characterized by progressive bone resorption and marked phenotypic heterogeneity. Despite advances in understanding Notch signaling in skeletal biology, longitudinal clinical data tracking disease evolution from early childhood through adolescence are lacking. Here, we report a rare longitudinal intrafamilial observation of HCS in a mother and her son carrying the same NOTCH2 pathogenic variant, providing novel insights into disease evolution and therapeutic response. Over extended follow-up, the son exhibited early vertebral fragility despite preserved or supranormal bone mineral density (BMD), whereas the mother developed severe osteoporosis, progressive acro-osteolysis, and multiple vertebral fractures. Longitudinal analysis revealed a dissociation between vertebral fragility and densitometric decline, challenging the paradigm that low BMD is the primary driver of skeletal morbidity in HCS. Treatment responses differed between the two patients, with bisphosphonate therapy in the son associated with stabilized BMD without altering vertebral structural progression, and denosumab in the mother associated with increased BMD, but not preventing progression of acro-osteolysis. Additionally, the emergence of extra-skeletal features during adolescence expands the phenotypic spectrum of HCS and suggests previously unrecognized systemic involvement. These data highlight intrinsic limitations of current therapeutic strategies and emphasize the need for targeted interventions addressing sustained Notch2 activation. Our findings contribute to the understanding of the natural history and therapeutic challenges of HCS, providing the framework for future mechanistic and translational research.