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To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound. The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones. CMA was performed in 66 cases of short long bones. There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) in pregnancies with no sonographic anomalies (P

To evaluate the long-term outcome of fetuses with a diagnosis of isolated short long bones. A retrospective review was conducted of all cases diagnosed with short long bones above 20 weeks of gestation during 2010–2017 in a single tertiary center. Exclusion criteria included abnormal sonographic findings other than short long bones, suspected genetic syndromes, chromosomal abnormalities, and abnormal Doppler flow indices. Follow-up was carried out by telephone questionnaire. During the study period, 54 (24.32%) women met inclusion criteria. Mean gestational age at delivery was 38.05 years (± 2.42 SD). Mean birth weight was 12–19th percentile according to the local fetal growth charts [2645 g (± 684 SD) 95% CI 2173–2980]. Median time for post-natal follow-up was 9.3 years (IQR 6.6–10.75). Growth below the 10th percentile was demonstrated in 27 (50%) children. 11 (20.37%) children were followed up by endocrinological clinics, of them 7 (12.96%) were treated with growth hormone. Three (5.6%) of the children were diagnosed with attention deficit hyperactivity disorder, an incidence that is considered lower than that of the general population (± 9%). Prenatal fetal isolated short long bones diagnosed during the late second and third trimester is associated with short stature. No neurodevelopmental impact was observed in our study group.

The most important difference between fractures in children and adults is the presence in the cartilaginous growth plates at the end of major long bones in children and at only one end of short long bones such as the metacarpals and metatarsals.

We report on a consanguineous Lebanese family in which a sister and brother had developmental delay, dysmorphic facial appearance, narrow chest, prominent abdomen, and short limbs. Neonatal radiographs disclosed a bell-shaped thorax, short ribs, some with a cupped end, severe platyspondyly, square iliac bones, horizontal acetabula with medial and lateral spurs, hypoplastic ischia, short long bones, slight widening of the distal femoral metaphyses, and absence of epiphyseal ossification of the knees. The girl died at age 9 months as a result of respiratory insufficiency. A clinical and radiological follow-up of the boy showed that the axial hypotonia, minor anomalies, and short stature were still present, whereas the bone abnormalities had improved. Differential diagnosis suggests that this is a new type of chondrodysplasia.

A familial short stature syndrome is described in two sisters. Clinical features include severe pre- and post-natal growth failure, stridor, feeding difficulties in the first 2 years requiring nasogastric feeding and facial dysmorphism reminiscent of Three M syndrome. Intellectual function is normal. Skeletal surveys show short long bones, small square iliac bones, short femoral necks and vertebral bodies which are short in the antero-posterior diameter with narrowing of the interpedicular distance inferiorly.

Disproportionate short stature is a heterogeneous group of hereditary disorders, which are classified according to their mode of inheritance, their clinical skeletal and non-skeletal manifestations, and their radiological characteristics. Herein, we inform on eight individuals with severe disproportionate short stature from two unrelated consanguineous families of Arab-Muslim ancestry. The adult height of the affected individuals is between 112 cm and 127 cm, and is due to pre- and post-natal growth retardation, which probably manifests as early as the second trimester of pregnancy. At a young age, the phenotype is characterized by a short stature, a relatively large head, and a long triangular face, and this phenotype later evolves to one with in which the head is relatively small, the mandible is large and pointy. The affected individuals have normal cognitive abilities and lack any neurological deficits. Other typical features include a prominent nose, a voice with an unusual high-pitched sound, relatively small ears, clinodactyly, brachydactyly, small hands, hypoplastic fingernails, a waddling gait, and sparse hair post-pubertally. Typical skeletal changes include short long bones, especially the femurs and humeri, with mild metaphyseal changes and very short femoral necks. After due consideration of the other hereditary causes of disproportionate short stature and close examination of the pedigrees of the two families, we concluded that these eight individuals have the same hitherto unreported form of severe disproportionate short stature that is inherited in the autosomal recessive mode.

Osteoscleroses are a heterogeneous group of bone remodeling disorders characterized by an increase in bone density. Here we report on a consanguineous Lebanese family in which two sisters, aged 39 and 36 years, exhibit a severe genu varum, a square-face appearance, high forehead, slight proptosis of the eyes, symmetric enlargement of the jaw, protruding chin, and short stature. Bone X-rays showed the presence of hyperostosis of the cranial base and vault with increased density of the orbits, hyperostosis of the bones, thickening of the cortices, diaphyseal modeling defects, cortical thickening of the medullary cavity, mild enlargement of the medullary cavity of the short long bones, short femoral necks, increased width of the ribs, and narrow interpedicular distances of the lower lumbar spine. Osteodensitometry showed values 200% to 300% above values for age. A cervical MRI revealed the presence of a diffuse osteosclerosis with calcification of the posterior vertebral ligament and a narrow canal between C2 and T2. Blood test results were unremarkable. Serum osteocalcin levels were in the normal range, whereas high values of serum C-telopeptide were noted. A bone biopsy showed only the presence of compact bone and did not allow for histomorphometric analysis. Molecular studies excluded genes known to be involved in sclerosing bone dysplasias as the cause of this condition. In vitro analysis of osteoclast function indicated that contrary to most cases of autosomal recessive osteopetrosis, osteoclasts both formed and resorbed but exhibited a small decrease in resorptive activity compared with osteoclasts generated from normal control individuals. Differential diagnoses are discussed, and the possibility that this may be a novel clinical entity is raised. (C) 2010 American Society for Bone and Mineral Research

Objective To establish the predictive value of an antenatal detection of ‘short long bones’ (SLBs) and/or IUGR in the diagnosis of skeletal dysplasia. Background The implications of SLBs remains unclear with only 51% (116/227) notifications of SLBs reported to the East Midlands and South Yorkshire Congenital Anomalies Register (EMSYCAR) between 2008–2012 exhibiting a limb reduction deformity at delivery. Conversely, over the same period, 360 cases delivered with a limb reduction deformity, or skeletal dysplasia/syndrome, which had not been reported antenatally with either SLBs or IUGR (birth prevalence 9.6/10,000). Methods Each of these 360 cases was individually reviewed. Those with completely missing limbs and digits, or congenital constriction bands, for which an antenatal diagnosis of SLBs is largely inappropriate, were excluded; 211 cases remained (birth prevalence 5.6/10,000). Results Of 211 cases; 50/211 (23.7%) were syndromic, associated either with short stature or more general limb dysplasia; 98 (46.4%) involved an upper or lower limb reduction deformity, 28 (13.2%) had more than one reduction anomaly. 33 (15.6%) exhibited lethal skeletal dysplasia, 25 (11.8%) non-lethal unspecified dysplasias and 15 (7.1%) various forms of osteogenesis. Over half; 56.9% (120) were liveborn, 36% (76) resulted in TOP. Conclusions While half of the cases notified antenatally with SLBs had a LRD at delivery, only a third of the total LRD cases were identified in this way. The remainder were correctly identified as skeletal dysplasias or LRDs from the earliest scan, suggesting that a description of SLBs has limited value as a soft marker.