Craniofacial dyssynostosis: case report and review

Craniofacial dyssynostosis (CFD) is a rare disorder related to premature closure of the lambdoid suture and the posterior part of the sagittal suture. Epilepsy, mental retardation, abnormalities of the corpus callosum, and short stature have been reported. We studied a patient with CFD, hydronephrosis, and partially empty sella turcica; the latter two features are reported for the first time. We discuss the brain anomalies and their neurologic sequelae, which are part of the CFD phenotype.     

Craniofacial dyssynostosis with cryptorchidism and normal stature

We describe an Arab boy with craniofacial dyssynostosis. He presented with facial anomalies, mental retardation, epilepsy, hypotonia, and agenesis of the corpus callosum. This report reemphasises the previously reported traits of craniofacial dysostosis syndrome and suggests that cryptorchidism represents part of the syndrome profile and that the presence of normal stature does not preclude the diagnosis. Am. J. Med. Genet. 79:5–7, 1998. © 1998 Wiley-Liss, Inc.     

Craniofacial dyssynostosis: description of the first four Spanish cases and review

Craniofacial dyssynostosis (CD) is characterized by premature fusion of the lambdoid and posterior part of the sagittal sutures, and short stature. Thus, the skull shape becomes dolichocephalic with protuberant forehead and either bulging or flat occiput. Facial changes are secondary to the skull defects, and some additional findings have also been described. We report on the first four known Spanish patients. They were unrelated and had Spanish ancestors. In the three previous reports about this syndrome, the authors hypothesized that the frequency of the gene causing CD must be rather high in the Spanish population, and relatively common in areas with Spanish ancestry. We have estimated the minimal birth prevalence of the syndrome in 0.51 per million livebirths. It has been previously suggested that the syndrome is inherited as an autosomal recessive trait, since there were two affected sisters among the nine published cases. Phenotypic variability is discussed in detail in this paper. We also underline several aspects for the anticipatory guidance of affected individuals, especially recommending a neurologic evaluation taking into account the radiologic findings in order to plan early interventions to avoid undesirable consequences of craniosynostosis. It is also recommended to perform additional studies (ophthalmologic, cardiologic, among others) to rule out the existence of associated anomalies, which are more frequent than previously considered.     

Extraocular eye muscles in human fetuses with craniofacial malformations: anatomical findings and clinical relevance

Anomalies of the extraocular muscles have been suspected to be present frequently in patients with craniofacial malformations. We studied the extraocular musculature in the orbits of 15 anencephalic human fetuses between the 5th and 10th months after gestation, and in one fetus with an occipital meningocele and a large defect of the left cranial base. The findings were compared to those in nine normal age-matched fetuses. All malformed fetuses exhibited special features of the levator palpebrae superioris muscle, either its absence, an anomaly of the muscle belly, or an anomalous insertion. In addition, deficient or aberrant muscle bellies of the oblique and rectus muscles were found. In anencephaly, the frontal bone is condensed, forming narrowed orbital cavities with hypotelorism. Frequent disturbance of extraocular muscle development in fetuses with craniofacial malformations is implicated. The presented specimens are examples of extreme variants of cranial and craniofacial malformation syndromes. Thus, similar findings of extraocular muscles might also be regularly found in clinically relevant craniofacial malformations. This would force new considerations about diagnostic and therapeutic approaches to patients with craniofacial malformations.     

New findings in short rib syndrome

This white infant, born at 37 weeks of gestation, had a large cranium, bilateral an ophthalmia, a middline cleft lip and palate, hypoplastic chest with short ribs, slightly protuberant abdomen, short limbs, bilateral single transverse palmar creases, a single unbilical artery, normal female external genitalia, normal (46 XY) chromosomes, and radiographic findings suggesting a short-rib (polydactyly) syndrome type IV (Beemer-Langer). Autopsy showed pulmonary hypoplasia, bilateral renal cystic dysplasia, intrahepatic bile duct cysts with periportal fibrosis, pancreatic cysts, absent internal genitalia, an atrophic optic chiasm, absent optic nerves, a single left anterior cerebral artery, polymicrogyria, and fusion of the frontal lobes, preoptic region, mammillary bodies, and thalami. © 1993 Wiley-Liss, Inc.     

A new skeletal dysplasia syndrome with dwarfism, craniofacial anomalies, and unique radiographic findings

We report on a boy from a consanguinous marriage who has a unique skeletal dysplasia, marked dwarfism, mild developmental delay, eye abnormalities, and cranofacial and skeletal changes that have not been described previously.     

FGF signaling in craniofacial biological control and pathological craniofacial development

Fibroblast growth factor receptors comprise a family of four evolutionarily conserved transmembrane proteins (FGFR1, FGFR2, FGFR3 and FGFR4) known to be critical for the normal development of multiple organ systems. In this review we will primarily focus upon the role of FGF/FGFR signaling as it influences the development of the craniofacial skeleton. Signaling by FGF receptors is regulated by the tissue-specific expression of FGFR isoforms, receptor subtype specific fibroblast growth factors and heparin sulfate proteoglycans. Signaling can also be limited by the expression of endogenous inhibitors. Gain-of-function mutations in FGFRs are associated with a series of congenital abnormality syndromes referred to as the craniosynostosis syndromes. Craniosynostosis is the clinical condition of premature cranial bone fusion and patients who carry craniosynostosis syndrome-associated mutations in FGFRs commonly have abnormalities of the skull vault in the form of craniosynostosis. Patients may also have abnormalities in the facial skeleton, vertebrae and digits. In this review we will discuss recent in vitro and in vivo studies investigating biologic mechanisms by which signaling through FGFRs influences skeletal development and can lead to craniosynostosis.     

Aarskog syndrome: New oral-facial findings

The Aarskog syndrome is characterized by short stature with typical facial, digital and genital anomalies. A further case is reported which presented with the uncommon finding of ophthalmoplegia and three previously unreported oral-facial findings: enamel dysplasia, a "col" deformity of the anterior mandible and a paresis of the facial muscles innervated by the VII cranial nerve. The implications of genetic heterogeneity in this nosologic classification are discussed.     

Secular change in craniofacial morphology

Five craniofacial variables (glabella–occipital length, basion–bregma height, maximum cranial breadth, nasion–prosthion height, and bizygomatic breadth) were used to examine secular change in morphology from the mid-19^th century to the 1970s. The 19^th century data were obtained from the Terry and Hamann-Todd anatomical collections, and the 20^th century data were obtained from the forensic anthropology databank. Data were available for Blacks and Whites of both sexes. Secular change was evaluated by regressing cranial variables on year of birth. Two analyses were conducted, one using the original variables and one using size and shape. Size is defined as the geometric mean of the cranial variables, and shape is the ratio of each variable to size. The results show remarkable changes in the size and shape of the cranial vault. Vault height increases in all groups in both absolute and relative terms. The vault also becomes longer and narrower, but these changes are less pronounced. Face changes are less than the vault changes, but to the extent that they occur, the face becomes narrower and higher. Overall cranial vault size has increased, but shape changes are greater than size changes. The magnitude of secular change in vault height exceeds that for long bones over a comparable time period, but follows a similar course, which suggests that vault height and bone length respond to the same forces. Changes in vault dimensions must occur by early childhood because of the early development of the vault. Am. J. Hum. Biol. 12:327–338, 2000. © 2000 Wiley-Liss, Inc.     

New insights into the relationship between suture closure and craniofacial dysmorphology in sagittal nonsyndromic craniosynostosis

Premature closure of the sagittal suture occurs as an isolated (nonsyndromic) birth defect or as a syndromic anomaly in combination with other congenital dysmorphologies. The genetic causes of sagittal nonsyndromic craniosynostosis (NSC) remain unknown. Although variation of the dysmorphic (scaphocephaly) skull shape of sagittal NSC cases has been acknowledged, this variation has not been quantitatively studied three‐dimensionally (3D). We have analyzed the computed tomography skull images of 43 infants (aged 0.9–9 months) with sagittal NSC using anatomical landmarks and semilandmarks to quantify and characterize the within‐sample phenotypic variation. Suture closure patterns were defined by dividing the sagittal suture into three sections (anterior, central, posterior) and coding each section as ‘closed’ or ‘fused’. Principal components analysis of the Procrustes shape coordinates representing the skull shape of 43 cases of NSC did not separate individuals by sex, chronological age, or dental stages of the deciduous maxillary first molar. However, analysis of suture closure pattern allowed separation of these data. The central section of the sagittal suture appears to be the first to fuse. Then, at least two different developmental paths towards complete fusion of the sagittal suture exist; either the anterior section or the posterior section is the second to fuse. Results indicate that according to the sequence of sagittal suture closure patterns, different craniofacial complex shapes are observed. The relationship between craniofacial shape and suture closure indicates not only which suture fused prematurely (in our case the sagittal suture), but also the pattern of the suture closure. Whether these patterns indicate differences in etiology cannot be determined with our data and requires analysis of longitudinal data, most appropriately of animal models where prenatal conditions can be monitored.     

New findings on virulence factors in Salmonella species]

The authors present a review of the literature on most recent findings pertaining to the properties of the most important factors of virulence of Salmonellae, in particular from the aspects of their biological and physico-chemical properties. These findings can contribute towards the elucidation of factors of pathogenicity and virulence of these microbes and mechanisms of the pathogenesis of diseases they produce.     

New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism

IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown.Material and methodsTargeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state.ResultsHere we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PROKR2/SPRY4/NSMF. These genes are known to contribute to the phenotype of hypogonadotropic hypogonadism, yet our results point to potential new “partners” underlying digenic and trigenic patterns.ConclusionsThe finding supports the importance of oligogenic inheritance and demonstrates the complexity of genetic architecture in hypogonadotropic hypogonadism. It also underlines the necessity for developing fine-tuned guidelines to provide a tool for adequate and precise sequence variant classification in non-Mendelian conditions.