Cleidocranial dysplasia (CCD) is a skeletal disorder with potential respiratory complications. We report a case of a 77-day-old male child with CCD who presents in respiratory distress. The infant was found to have a unilateral lung herniation secondary to an acute viral illness. This case highlights the importance of keeping CCD in the differential diagnosis of a neonate in respiratory distress.

Cyprinids include some of the most widely farmed freshwater species. The aim of this study was to assess the incidence of skeletal malformations in carp species reared in semi-intensive systems in Albania: common carp (Cyprinus carpio), silver carp (Hypophthalmichthys molitrix), grass carp (Ctenopharyngodon idella) and bighead carp (Hypophthalmichthys nobilis). The common carp fingerlings had a mean total length of 28.9 ± 5.0 mm; the frequencies of individuals with at least one anomaly and at least one severe anomaly were 79.2% and 43.4%, respectively. The silver carp juveniles had a mean total length of 21.6 ± 2.1 mm; the frequencies of individuals with at least one anomaly and one severe anomaly were 93.1% and 57.5%, respectively. The grass carp fry had a mean total length of 33.5 ± 2.6 mm; all the analyzed specimens showed almost one anomaly and 86.4% showed at least one severe anomaly. The bighead carp juveniles had a mean total length of 34.4 ± 5.7 mm; the frequencies of individuals with at least one anomaly and at least one severe anomaly were 95.0% and 62.5%, respectively. The development of a more suitable feeding protocol for herbivorous species and the setting up of more efficient broodstock management protocols are suggested to reduce the high incidence of skeletal malformations.

15q26 deletion is a rare genomic disorder characterized by intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and congenital malformations. Here, we report a 4-month-old female with intrauterine growth retardation, short stature, pulmonary hypertension, atrial septal defect and congenital bowing of long bones of the legs. Chromosomal microarray analysis showed a de novo deletion of approximately 2.1 Mb at 15q26.3 region that does not include IGF1R. Our analysis of patients documented in the literature and the DECIPHER database with 15q26 deletions distal to IGF1R, including 10 patients with de novo pure deletions, allowed us to define the smallest region of overlap to 686 kb. This region includes ALDH1A3, LRRK1, CHSY1, SELENOS, SNRPA1, and PCSK6. We propose haploinsufficiency of one or more genes, besides IGF1R, within this region may contribute to the clinical findings in patients with 15q26.3 deletion.

FOXC1 is a ubiquitously expressed forkhead transcription factor that plays a critical role during early development. Germline pathogenic variants in FOXC1 are associated with anterior segment dysgenesis and Axenfeld-Rieger syndrome (ARS, #602482), an autosomal dominant condition with ophthalmologic anterior segment abnormalities, high risk for glaucoma and extraocular findings including distinctive facial features, as well as dental, skeletal, audiologic, and cardiac anomalies. De Hauwere syndrome is an ultrarare condition previously associated with 6p microdeletions and characterized by anterior segment dysgenesis, joint instability, short stature, hydrocephalus, and skeletal abnormalities. Here, we report clinical findings of two unrelated adult females with FOXC1 haploinsufficiency who have ARS and skeletal abnormalities. Final molecular diagnoses of both patients were achieved using genome sequencing. Patient 1 had a complex rearrangement involving a 4.9 kB deletion including FOXC1 coding region (Hg19; chr6:1,609,721-1,614,709), as well as a 7 MB inversion (Hg19; chr6:1,614,710-8,676,899) and a second deletion of 7.1 kb (Hg19; chr6:8,676,900-8,684,071). Patient 2 had a heterozygous single nucleotide deletion, resulting in a frameshift and a premature stop codon in FOXC1 (NM_001453.3): c.467del, p.(Pro156Argfs*25). Both individuals had moderate short stature, skeletal abnormalities, anterior segment dysgenesis, glaucoma, joint laxity, pes planovalgus, dental anomalies, hydrocephalus, distinctive facial features, and normal intelligence. Skeletal surveys revealed dolichospondyly, epiphyseal hypoplasia of femoral and humeral heads, dolichocephaly with frontal bossin gand gracile long bones. We conclude that haploinsufficiency of FOXC1 causes ARS and a broad spectrum of symptoms with variable expressivity that at its most severe end also includes a phenotype overlapping with De Hauwere syndrome.

Gilthead seabream (Sparus aurata) production is a highly valued aquaculture industry in Europe. The presence of skeletal deformities in farmed gilthead seabream represents a major bottleneck for the industry leading to economic losses, negative impacts on the consumers\' perception of aquaculture, and animal welfare issues for the fish. Although past work has primarily focused on the hatchery phase to reduce the incidence of skeletal anomalies, this work targets the successive pre-ongrowing phase in which more severe anomalies affecting the external shape often arise. This work aimed to test the effects of: (i) larger and smaller tank volumes, stocked at the same density; and (ii) higher and lower stocking densities maintained in the same water volume, on the skeleton of gilthead seabream fingerlings reared for ~63 days at a pilot scale. Experimental rearing was conducted with gilthead seabream juveniles (~6.7 ± 2.5 g), which were selected as \'non-deformed\' based on external inspection, stocked at three different densities (Low Density (LD): 5 kg/m3; Medium Density (MD): 10 kg/m3; High Density (HD): 20 kg/m3) in both 500 L and 1000 L tanks. Gilthead seabream were sampled for growth performance and radiographed to assess the skeletal elements at the beginning and end of the experimental trial. Results revealed that (i) LD fish were significantly longer than HD fish, although there were no differences in final weights, regardless of the water volume; (ii) an increase in the prevalence of seabream exhibiting cranial and vertebral axis anomalies was found to be associated with increased density. These results suggest that farmers can significantly reduce the presence of some cranial and axis anomalies affecting pre-ongrown gilthead seabream by reducing the stocking density.

Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1; OMIM#213980) is a rare autosomal recessive disorder characterized by the clinical triad of developmental delay and/or intellectual disability, a typical facial gestalt with brachycephaly, highly-arched bushy eyebrows, synophrys, hypertelorism, wide nasal bridge, and short nose, as well as multiple vertebrae and rib malformations, such as bifid and fused ribs and abnormal vertebral segmentation and fusion. Biallelic loss-of-function variants in TMCO1 cause CFSMR1. We report on two unrelated Egyptian patients with a phenotype suggestive of CFSMR. Single whole-exome sequencing in patient 1 and Sanger sequencing of TMCO1 in patient 2 revealed the same homozygous TMCO1 nonsense variant c.187C > T/p.(Arg63*) in both affected individuals; patients\' healthy parents were heterozygous carriers of the variant. Congenital hearing loss in patients 1 and 2 is an occasional finding in individuals affected by CFSMR. Camptodactyly and syndactyly, which were noted in patient 2, have not or rarely been reported in CFSMR. Review of the literature revealed a total of 30 individuals with the clinically recognizable and unique phenotype of CFSMR1, including the patients reported here, who all carried biallelic TMCO1 variants. Six different TMCO1 variants have been reported in the 30 patients from 14 families, comprising three nonsense, two 2-bp deletions, and a splice donor site variant. All disease-associated TMCO1 variants likely represent null alleles resulting in absence of the encoded protein. TMCO1 has been proposed to act as a Ca2+ channel, while other data revealed TMCO1 as a mitochondrial protein and a component of the translocon at the endoplasmic reticulum, a cellular machinery important for the biogenesis of multi-pass membrane proteins. RAB5IF/C20orf24 has recently been identified as causative gene for craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-2 (CFSMR2; OMIM#616994). Heterodimerization of RAB5IF/C20orf24 and TMCO1 and their interdependence may suggest a pathophysiological role of ER-mitochondria interaction underlying CFSMR.

OBJECTIVE: The main objective of this study is to get a wider and clearer idea about the relationship between sella turcica bridging and the type of dental anomalies related to size, shape, number, structure and eruption of teeth.
METHODS: For the present study, 50 pretreatment lateral cephalometric radiographs showing complete sella turcica bridging were retrieved from the 500 existing case records of patients. The control group consisted of 50 pretreatment lateral cephalograms without sella turcica bridging retrieved from the same case records by using simple random sampling. After collection of the samples, retrospective study was performed with the analysis of patient records to assess any associated dental anomaly in patients with sella turcica bridging and patients without sella turcica bridging. Shafer\'s classification of morphological variations in size, shape, structure, number and eruption of teeth was used to analyze and group the dental anomalies.
RESULTS: The incidence of dental anomalies related to number and size of teeth was found to be higher in cases with sella turcica bridging.
CONCLUSIONS: Lateral cephalogram is used by orthodontist routinely for diagnosis and treatment planning; it can be used as a prediction tool for dental anomalies as well. Early detection of skeletal anomalies can be used to forecast the presence of dental anomalies later in life, which will help the clinician to adopt preventive measures.

OBJECTIVE: Skeletal system abnormalities are a heterogenous group of disorders caused by teratogens, environmental factors, chromosomal abnormalities or monogenic disorders. Monogenic causes of the skeletal disorders in postnatal patients are periodically revised by the International Skeletal Dysplasia Society (ISDS) and published as Nosology and Classification of Genetic Skeletal Disorders. The aim of this study was to analyze genetic causes of the skeletal system abnormalities diagnosed by prenatal sonography and to establish diagnostic protocol with regard to extended genetic testing in this group of patients.
METHODS: The study included all consecutive patients with sonographic abnormalities of the skeletal system in singleton pregnancies evaluated in a single ultrasound department during one year.
RESULTS: The study group consisted of 55 fetuses. Chromosomal abnormalities were detected in 24 fetuses. Single gene pathogenic or likely pathogenic variants in 14 different genes were detected in 18 fetuses. Seven genes have already been listed in the ISDS Nosology. The remaining seven genes were out of this list.
CONCLUSIONS: In fetuses with localized abnormality of the skeletal system accompanied by additional structural anomalies chromosomal abnormality is the most common diagnosis. Exome sequencing increases the diagnostic yield in fetuses with skeletal system abnormalities especially in case of multiple abnormalities. This article is protected by copyright. All rights reserved.

Retinoic acid exposures as well as defects in the retinoic acid-degrading enzyme CYP26B1 have teratogenic effects on both limb and craniofacial skeleton. An initial report of four individuals described a syndrome of fetal and infantile lethality with craniosynostosis and skeletal anomalies caused by homozygous pathogenic missense variants in CYP26B1. In contrast, a 22-year-old female was reported with a homozygous missense pathogenic variant in CYP26B1 with complex multisuture craniosynostosis and intellectual disability, suggesting that in some cases, biallelic pathogenic variants of CYP26B1 may be compatible with life. Here we describe four additional living individuals from two families with compound heterozygous pathogenic missense variants in CYP26B1. Structural assessment of these additional missense variants places them further from the catalytic site and supports a model consistent with milder nonlethal disease. In addition to previously reported findings of multisuture craniosynostosis, conductive hearing loss, joint contractures, long slender fingers, camptodactly, broad fingertips, and developmental delay/intellectual disability, skeletal imaging in our cases also revealed gracile long bones, gracile ribs, radioulnar synostosis, and carpal and/or tarsal fusions. These individuals broaden the phenotypic range of biallelic pathogenic variants in CYPB26B1 and most significantly clarify that mortality can range from perinatal lethality to survival into adulthood.

A malformed pectoral joint of the middle Devonian antiarch fish Asterolepis ornata is described, and a survey of congenital malformations in the fossil record is provided.
The specimen of A. ornata (MB.f.73) from Ehrman in Latvia, stored at the Museum für Naturkunde Berlin, Germany.
A. ornata was macroscopically and radiologically investigated, and the overview on congenital malformation was based on an extensive literature survey.
In the deformed joint of A. ornata, the articular surfaces and muscle attachment sites are greatly reduced, indicating restricted mobility. Congenital malformations can be found since the middle Silurian and affect all groups of vertebrates, but they are rare. Teeth and the vertebral column are the most commonly affected anatomical regions, and the mechanisms causing these malformations probably remained the same through geological time.
Micro-CT of the deformed joint shows no disturbance of the normal trabecular pattern and no evidence of trauma or disease, suggesting a congenital hypoplasia, although an acquired deformity cannot be ruled out completely.
Congenital malformations, even those that are rare, were part of the common history of vertebrates for more than 400 million years.
Epidemiologic measures like incidence and prevalence usually cannot be applied to define rare diseases in the fossil record.
A broadly based analysis of species of fossil vertebrates with numerus recovered specimens (e.g. many bony fishes, amphibians, certain dinosaurs) might statistically affirm the occurrence of malformations and possible correlations with the paleoenvironment.