1/91. Prenatal sonographic features of spondylocostal dysostosis and diaphragmatic hernia in the first trimester. Spondylocostal dysostosis is a congenital disorder characterized by multiple malformations of the vertebrae and ribs. We describe the sonographic features of an affected fetus at 12 and 14 weeks of gestation. The fetus had thoracic scoliosis, multiple vertebral and rib malformations and a grossly dilated stomach that had herniated into the chest through a left-sided diaphragmatic hernia. The stomach spanned the whole length of the fetal trunk. ( info) |
| patients with spondylocostal dysostosis (SCD) have vertebral abnormalities and numerical or structural rib anomalies that produce thoracic asymmetry. Rib anomalies and dysmorphism are the typical features that differentiate this syndrome from spondylothoracic dysostosis (STD). Jarcho-Levin syndrome is a severe form with involvement of the whole vertebral column. Other associated findings such as congenital heart defects, abdominal wall malformations, genitourinary malformations and upper limb anomalies may be found; in addition, neural tube defects (NTDs) have been associated with this malformation. SCD is transmitted both in a recessive form and as a dominant defect. We report on 3 children with SCD; 2 also had NTDs. All of them were studied with x-rays and spinal magnetic resonance (MR), and over the same period they underwent multidisciplinary clinical functional evaluation. One of our cases with NTD also presented polythelia, which has not previously been described in patients with SCD. The common association of segmental costovertebral malformations with NTDs could be related to an early gastrulation genomic defect, or one after gastrulation, when there are two independent somitic columns. The latter sometimes progresses and then involves primary and secondary neurulation. Also, the association of SCD with NTDs could be related to the interaction of different genes, resulting in this complex phenotype. Therefore, additional genetical and embryological studies are necessary to provide evidence of an etiological link between SCD and NTD. ( info) |
3/91. Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin k protein. Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin k gene. cathepsin k, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. dna sequence analysis of the cathepsin k gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin k polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin k levels do not have any phenotypic effect, whereas absent cathepsin k results in pycnodysostosis. ( info) |
4/91. Prenatal ultrasound diagnosis of a femur-fibula-ulna complex during the first half of pregnancy. A case of fetal femur-fibula-ulna (FFU) complex diagnosed by ultrasound is presented. Ultrasonographic features of a fetus displaying bilateral femoral hypoplasia, aplasia of the right forearm and the right hand, ray defects of the left hand are described. The importance of an early diagnosis of this malformation is emphasized with respect to parental counselling concerning prognosis and further prenatal management. ( info) |
5/91. Frontonasal dysostosis in two successive generations. Frontonasal dysostosis (also called frontonasal "dysplasia") comprises ocular hypertelorism, median facial cleft affecting nose and/or upper lip, unilateral or bilateral cleft of the alae nasi, anterior cranium bifidum occultum, or a widow's peak. Usually it is a sporadic disorder, although a few familial cases have been reported. We describe a 2-year-old girl with anterior cranium bifidum occultum, lipoma of genu and anterior part of the corpus callosum, and hypertelorism. Her mother had a history of a nasal drip at birth caused by a defect in the cribriform plate and phenotypically, a widow's peak. This observation suggests either autosomal dominant or X-linked dominant inheritance. The family illustrates the importance of identifying mild expression of frontonasal dysostosis before genetic counseling. ( info) |
6/91. The Richieri-Costa and Pereira form of acrofacial dysostosis: first case in a non-Brazilian infant. We report on a French boy with cleft mandible, pre/postaxial hand anomalies, and clubfoot born to consanguineous parents. These findings are comparable to those of previous cases of the autosomal recessive Richieri-Costa and Pereira syndrome of short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot. This is the first case in a non-Brazilian infant. ( info) |
7/91. Pyknodysostosis: a report of two siblings with unusual manifestations. We report pyknodysostosis presenting as extramedullary haematopoiesis in one of two siblings and as obstructive airway disease in the other. Visceral manifestations are rare and have been reported in only two cases in the Indian literature. They have often been mistaken for osteopetrosis, haemolytic anaemia and other osteochondrodystrophies. The cases we report illustrate that, though the physical characteristics may be similar, it is the radiological features that are typical and help establish the diagnosis. ( info) |
8/91. De novo translocation (8;12) and frontofacionasal dysplasia in a newborn boy. We describe a newborn boy one of triplets, whose karyotype was 46,XY, t(8;12)(q22;q21). prenatal diagnosis of multiple craniofacial anomalies had been made. Following delivery, the patient was thought to exhibit findings consistent with a diagnosis of frontofacionasal dysostosis. We hypothesize that one of the break points of this translocation may involve a gene essential to craniofacial development. ( info) |
9/91. Thoracic-pelvic dysostosis. We report a third patient, a female, with thoraco-pelvic dysostosis. This rare disorder is similar in phenotypic and radiographic appearances to thoraco-laryngo-pelvic dysplasia (Barnes syndrome). The only major difference between these two diseases is absence of laryngeal involvement in thoraco-pelvic dysplasia. They may represent two different entities or a contiguous gene syndrome. ( info) |
10/91. New dysostosis showing multilevel absence of vertebral pedicles: unique developmental anomaly of vertebral arches? We report on an apparently normal child who shows hypopaplasia of the vertebral pedicles and posterior arches of several cervical, thoracic, and lumbar vertebrae with normally fused spinous apophyses, hypoplastic sacrum, lumbar epidural lipomatosis, synostoses of some cervical vertebral disks, and sacral spina bifida. The most likely mechanism is an abnormal differentiation of the spinal processes, due most probably to an absence of differentiation in cartilage of the dense mesenchyme forming their most anterior part. Because the anomalies affect multiple levels, we highly suspect a genetic basis to this unusual dysostosis affecting the development of the posterior sclerotomes. ( info) |