Genetic heterogeneity in spondylo-epi-metaphyseal dysplasias: a clinical and radiological study

Spondylo-epi-metaphyseal dysplasias [SEMD] are a heterogeneous group of skeletal disorders characterized by defective growth and modeling of the spine and long bones. Different types are described in the literature. Accurate classification of SEMDs is essential for proper genetic counseling. This study included 20 cases of SEMDs diagnosed by clinical and radiological findings. Cases were classified based on additional associated clinical and/or radiological features into 7 subtypes. Different subtypes were discussed with review of the literature. The study illustrated the heterogeneity of SEMDs and emphasized the importance of detailed and meticulous clinical genetic and biochemical evaluation in addition to comprehensive radiological investigations for such group of disorders. It also recommends further molecular studies to identify the molecular bases of the different types

Clinical, oro dental and cytogenetic studies in some cases of papillon-lefevre syndromes and prepubertal periodontitis

Prepubertal peripdontitis is a rapidly prognessive form of early onset periodontitis leading to destruction of the periodontal support of the primary and secondary dentition. The aim of this study is to determine the basics for genetic mapping of six Egyptian cases suffering from prepubertal periodontitis and its variants. After completion of clinical assessment, cytogenetic study was performed for all cases including chromosomal analysis and plain X-ray for their hands. The gentic study revealed arachnodactyly of their hands, However no radiographic deformity of their fingers was detected. The cytogenetic study for all patients did not show any abnormality. This study might have important implications on oral public health, and in diagnosis and treatment of periodontitis

Genetic studies of congenital contractures of limbs

Congenital contractures of limbs comprise a category of limb malformations that poses a difficult diagnostic and therapeutic problem. They can occur as an isolated defect or as part of syndromes. This study included 46 patients with congenital contractures of limbs. Cases were referred to the Limb and Skeletal Anomaly Clinic at the National Research Centre. Detailed family history, pedigree construction, physical and orodental examination, anthropometric measurements and radiological studies were carried out for all cases. Cytogenetic analysis using G-banding and high resolution techniques were carried out for 36 cases. Biochemical and neurophysiologic studies were conducted for selected cases. According to clinical phenol-type, cases were classified into 4 main categories, which were further subdivided into 16 entities. Category [I]: included congenital contractures that affected primarily the musculoskeletal system, 18 cases were in this category comprising 8 entities. Category [II]: Twenty cases had musculoskeletal involvement in addition to other system malformations or anomalies comprising 5 entities, of which 11 cases had multiple pterygium syndrome. Category [III]: Six patients in this study had musculoskeletal involvement plus lethality, CNS anomalies or mental retardation. Four were diagnosed as Pena-Shokeir syndrome, one with Aase-Smith syndrome and another case showed dup [1] [p36.1-36.2]. Category [IV]: Contracture deformities of limbs due to environmental factors, which were present in 2 cases only. Detailed genetic and clinical analysis of different cases with congenital contractures of limbs are presented in this study. Our work proved that contracture deformities of limbs due to genetic causes were the most common [44 cases], while those related to environmental causes were only present in 2 cases. This emphasizes the importance of careful clinical examination and categorization o patients with congenital contracture! of limbs and the necessity of proper genetic counseling of affected families. The study of the molecular causes of these disorders is important for the understanding of the pathogenesis hoping for their prevention, early intervention and gene therapy

Comparison between isolated ectrodactyly and split hand / split foot as a part of syndromes: Clinical and orodental studies

Ectrodactyly is a developmental disorder that describes the partial or total absence of distal segments of the hand with the proximal segments more or less normal. The malformation can occur either isolated or associated with other systemic anomalies as a part of syndromes. Split hand/ split foot malformation [SHFM], associated with syndactyly of digits on both sides of the deficiency, is a longitudinal axial reduction defect, which is also either isolated or as a part of syndromes. This study included 2 patients with isolated ectrodactyly and 6 cases with split hand/split foot as a part of 2 syndromes; 5 of which were consistent with the ectrodactyly, ectodermal dysplasia, cleft lip and palate syndrome [EEC syndrome] and 1 female patient with ectrodactyly, ectodermal dysplasia, macular dystrophy syndrome [EEM syndrome]. Pedigree analysis, detailed physical examination, orodental studies and X-ray examination of hands, feet and teeth were done for all cases. Complete eye evaluation, hearing assessment and pelvi-abdominal ultrasound were carried out for syndromic cases. Chromosomal analysis was done for all patients. Our results showed that the 2 isolated cases with ectrodactyly were unilateral and sporadic with some evidence of multifactorial etiology. Cases with EEC syndrome showed variable degrees of SHFM, manifestations of ectodermal dysplasia in the form of sparse hair, eyebrows and eye lashes, microdontia, dysplastic nails and dry skin in addition to cleft lip and palate. Other orodental features included enamel hypoplasia, xeroderma and tooth decay. Lacrimal duct obstruction, microphthalmia, anophthalmia, photophobia and conjunctivitis were evident ocular manifestations in some cases. All our patients were sporadic with high paternal age in two cases suggesting dominant mutation. In our patient with EEM syndrome macular dystrophy was present in association with ectrodactyly and ectodermal dysplasia in the form of fair sparse hair and eyebrows as well as an albinoid fundus. Being the offspring of consanguineous young parents confirmed the autosomal recessive pattern of inheritance in the EEM syndrome. Chromosomal studies were normal in all studied cases. This study clarifies the importance of meticulous examination of patients with reduction defects and their family members and the search for associated anomalies in order to reach a proper diagnosis and provide accurate genetic counseling. For proper genetic counseling it is also important to clarify the terminology of ectrodactyly as an isolated defect and to differentiate between this sporadic digital anomaly and the inherited split hand/split foot either as an isolated defect or as a part of syndromes

Anophthalmia/microphthalmia: clinical, ophthalmological and imaging findings

This study described the craniofacial anomalies in correlation with ocular, intracranial, cytogenetic and electro- physiological findings in children with anophthalmia/microphthalmia. Twenty cases with congenital anophthalmia/microphthalmia [11 males, 9 females with age range from 8 days to 9.5 years] were examined. Seventeen cases had bilateral clinical anophthalmia/microphthalmia, while three cases had unilateral microphthalmia/anophthalmia. Patients with clinical anophthalmos/microphthalmia had associated congenital brain malformations [10/20 patients, 50%], genital anomalies [6/20, 30%] and major congenital orodental abnormalities [2/18 patients, 11.1%]. Eight cases of 11 with bilateral microphthalmia [72.7%] were reported to have bilateral congenital cataract. In addition, 6 cases [6/10, 60%] had abnormal visual evoked potentials [VEP] and electroretinogram [ERG]. The results presented the correlation between VEP and clinical, neuroimaging picture and/or the ophthalmological abnormalities. Eye defects are heterogeneous, since they were observed in clinical patterns with all modes of inheritance. Autosomal-recessive syndromes represent 55% of total syndromes, followed by syndromes of autosomal-dominant inheritance [15%], X- linked dominant [10%], chromosomal structural abnormalities [10%] and caused by environmental agents [10%]. Nevertheless, high rate of consanguinity [11 cases, 55%] with mean inbreeding coefficient of 0.0512 and the similarly affected sibs highlight the role of single gene disorder in the country. The contribution of electrophysiology of the eye, MRI of brain, cytogenetic and orodental examinations were useful for better determination of visual function and identification of potential underlying multisystem disease, subsequently, improving parental understanding and genetic counseling