RESUMEN
BACKGROUND: Namaqualand hip dysplasia (NHD) is a mild form of spondyloepiphyseal dysplasia in which progressive arthropathy of the hip joint is a major manifestation. The disorder was documented in a multigenerational South African (SA) family with antecedents from Namaqualand, a region in the north-west of the country. Linkage analysis revealed a locus that includes the collagen type II gene, COL2A1. OBJECTIVES: To identify the pathogenic COL2A1 variant causing NHD in an SA family. METHODS: One affected male with a clear diagnosis of NHD was selected for whole-exome sequencing (WES) on the Ion Torrent Proton platform. A probe-based assay and direct cycle sequencing were used to confirm that the prioritised variant segregated with the phenotype in the NHD family and was not present in unrelated controls from the same population. RESULTS: WES identified one heterozygous variant, c.2014G>T; p.(Gly672Cys), in the coding sequence of the COL2A1 gene. The variant segregated with NHD in 23 affected family members and was previously reported in a Caucasian male with Perthes disease-like presentation. CONCLUSIONS: It is now possible to provide a molecular diagnosis of NHD before hip problems present. The large, clinically well-characterised NHD family is a valuable resource that could provide more insight into the mechanisms responsible for the variable expression observed in individuals with this variant.
Asunto(s)
Colágeno Tipo II/genética , Luxación Congénita de la Cadera/diagnóstico , Osteocondrodisplasias/congénito , Adulto , Niño , Secuenciación de Nucleótidos de Alto Rendimiento , Luxación Congénita de la Cadera/genética , Luxación Congénita de la Cadera/fisiopatología , Humanos , Enfermedad de Legg-Calve-Perthes/diagnóstico , Enfermedad de Legg-Calve-Perthes/genética , Masculino , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/fisiopatología , Sudáfrica , Secuenciación del ExomaRESUMEN
BACKGROUND: The maxillofacial and dental manifestations of Osteogenesis imperfecta (OI) have significant implications in terms of management. Although the occurrence of abnormal dentine in some forms of OI is well documented, there is scant information on the association of abnormal dentine in the Black African persons with phenotypic OI III and genotypic OI XI in South Africa. METHODS: This was a cross-sectional analytic study. A series of 64 Black South African individuals with a confirmed phenotypic diagnosis of OI III, ages ranging from 3 months to 29 years, were assessed clinically, radiographically, and at a molecular level. RESULTS: A total number of 64 saliva samples were analyzed and 3 DNA variations were identified in exon 5 of the FKBP10 gene. The homozygous mutation, c.[831dupC]; [831dupC], was identified in 23 affected persons who had no clinically obvious features of DI in their primary and secondary teeth. Radiologically, mild features of DI were evident in 10 persons in whom radiographic images were obtained and were given a Clinical-radiological score of 2. A compound heterozygous mutation, c. [831delC]; [831dupC], was identified in three siblings. An intraoral examination of these affected persons revealed no clinically apparent features of DI in their primary and secondary teeth. Due to the lack of radiological facilities, the presence or absence of DI could not be confirmed or negated. A second compound heterozygous mutation, c.[831dupC]; [1400-4C>G], was identified in a female of 29 years belonging to the Xhosa linguistic group. Her teeth appeared clinically normal but it was not possible to obtain radiographs. In 37 affected individuals, no disease-causing mutations were identified. CONCLUSION: Black African individuals in SA with the homozygous mutation in the FKBP10 gene have clinically unaffected teeth yet exhibited radiographic features of DI to varying degrees. This characterization is suggestive of a relationship between the genetic abnormality and the clinical manifestations of DI. The authors suggest that this diagnosis must include teeth that are clinically and/or radiologically aberrant, and should not exclude the presence of other, milder, dentinal aberrations associated with OI. There was no correlation between severity of OI and DI in this cohort of individuals.
RESUMEN
Hereditary dentine dysplasias (HDD) such as dentinogenesis imperfecta (DI) and dentine dysplasia (DD) are a group of genetic conditions characterised by an abnormal dentine structure due to disturbances in the formation, composition, or organisation of the dentine matrix. Either the primary or both primary and secondary dentition are affected to varying degrees. These disorders result from mutations in the genes encoding the major protein constituents of dentine, notably collagens and phosphoproteins. The clinical and radiological features of the hereditary dentine dysplasias (HDD) are relevant to clinical dentistry, in particular osteogenesis imperfecta (OI) which is a well-known heterogeneous genetic disorder. OI is currently the focus of considerable academic attention and involvement of the teeth is a frequent and variable manifestation. In this analysis, the literature related to the classification, clinical features, and molecular pathogenesis of heritable structural tooth diseases affecting dentine formation is reviewed. The definition, history of the terminology and the development of the current classification is outlined and discussed in detail with the aim to address semantic confusion that has arisen in the literature on HDD and to provide clarity on the use of appropriate terminology in the context of OI.
Asunto(s)
Dentinogénesis Imperfecta , Osteogénesis Imperfecta , Terminología como Asunto , Dentina , Dentición Permanente , Humanos , DienteRESUMEN
A South African girl with CANDLE Syndrome is reported with emphasis on the orodental features and dental management. Clinical manifestations included short stature, wasting of the soft tissue of the arms and legs, erythematous skin eruptions and a prominent abdomen due to hepatosplenomegaly. Generalized microdontia, confirmed by tooth measurement and osteopenia of her jaws, confirmed by digitalized radiography, were previously undescribed syndromic components. Intellectual impairment posed problems during dental intervention. The carious dental lesions and poor oral hygiene were treated conservatively under local anaesthetic. Prophylactic antibiotics were administered an hour before all procedures.Due to the nature of her general condition, invasive dental procedures were minimal. Regular follow-ups were scheduled at six monthly intervals. During this period, her overall oral health status had improved markedly.The CANDLE syndrome is a rare condition with grave complications including immunosuppression and diabetes mellitus. As with many genetic disorders, the dental manifestations are often overshadowed by other more conspicuous and complex syndromic features. Recognition of both the clinical and oral changes that occur in the CANDLE syndrome facilitates accurate diagnosis and appropriate dental management of this potentially lethal condition.
Asunto(s)
Caries Dental/terapia , Eritema Nudoso/complicaciones , Dedos/anomalías , Niño , Tomografía Computarizada de Haz Cónico , Caries Dental/etiología , Eritema Nudoso/terapia , Femenino , HumanosRESUMEN
Spondyloepimetaphyseal dysplasia with joint laxity (SEMD-JL), type 1 is an autosomal recessive disorder which has been identified in more than 30 affected children in the Afrikaans-speaking community of South Africa. Sequencing of B3GALT6 revealed a specific mutation, c.235A > G, in homozygous form in four families, while three others were compound heterozygotes for this mutation in combination with the c.200C > T mutation. In addition, a proband from one family carried the c.16C > T mutation combined with c.200C > T. In a series of five Iranian persons, mutations in B3GALT6 have been implicated in a syndrome characterised by skeletal abnormalities with intellectual disability, bone and connective tissue fragility. Other mutations in B3GALT6 resulted in the classical SEMD-JL phenotype in seven Japanese families and in a syndrome which has been likened to a progeroid form of Ehlers-Danlos syndrome (EDS). It is evident that there is considerable intragenic heterogeneity in B3GALT6. One of the mutations, c.200C > T, in the affected South Africans was also present in one of the Japanese persons and the respective phenotypes were identical. The multiplicity of allelic mutations and the phenotypic differences in the affected persons supports the concept that a spectrum of connective tissue disorders is programmed by mutations in B3GALT6.
Asunto(s)
Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/genética , Mutación , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Alelos , Sustitución de Aminoácidos , Niño , Análisis Mutacional de ADN , Familia , Humanos , Linaje , Fenotipo , Polimorfismo de Nucleótido Simple , SudáfricaRESUMEN
Tricho-rhino-phalangeal Syndrome (TRPS) is a rare inherited dysplasia affecting hair, nasal structure and fingers. A literature review indicated that since first described, three types of manifestations have been identified. A Table summarising the oral manifestations demonstrates the variety of presentations. A South African male child presented with the syndrome and was found to show premature eruption of permanent teeth, a finding that has not been previously reported. His oro-facial manifestations also included malaligned and unerupted crowded teeth, bulbosity of the nasal tip and an elongated philtrum and evidence of mild intellectual impairment. A protocol has been developed to guide the future management of these cases.
Asunto(s)
Dedos/anomalías , Cabello/anomalías , Enfermedades de la Boca/diagnóstico , Nariz/anomalías , Enfermedades Dentales/diagnóstico , Anomalías Múltiples/patología , Preescolar , Estudios de Seguimiento , Gingivitis Ulcerosa Necrotizante/diagnóstico , Halitosis/diagnóstico , Humanos , Masculino , Prognatismo/diagnóstico , Síndrome , Erupción Dental/fisiologíaRESUMEN
OBJECTIVES: To determine the range of genetic disorders in the Indian population of South Africa, assess relevant historical and demographical factors, and discuss the implications for medical and genetic care. METHODS: WSW reviewed the archived data pertaining to patients seen in his paediatric practice in Durban during the past 45 years. Likewise, PB reviewed case details of persons encountered since 1972 in Cape Town, at outreach clinics, and in special institutions for the handicapped throughout South Africa. Additional information was accessed through the Cape Genetic Heritage archive. RESULTS: In addition to the common ubiquitous worldwide genetic disorders, several rare heritable conditions are present in the Indian community of South Africa. These disorders are the consequence of the founder effect and reflect the biological heritage of the early immigrants. Demographic factors (notably endogamy) are also relevant in this respect. As a result of these processes, thalassaemia is by far the most common and important genetic disorder in the Indian population in the country. CONCLUSION: Awareness of the presence of specific genetic conditions in the Indian community of South Africa is important in the diagnostic process. In turn, diagnostic precision facilitates accurate prognostication and optimal medical and genetic management.
Asunto(s)
Enfermedades Genéticas Congénitas/epidemiología , Trastornos de los Cromosomas/epidemiología , Sordera/congénito , Sordera/epidemiología , Diabetes Mellitus/epidemiología , Humanos , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , India/etnología , Sudáfrica/epidemiología , Talasemia/epidemiologíaRESUMEN
The major manifestations of the Wolf-Hirschhorn syndrome are developmental delay, short stature, mental impairment and epilepsy. Clefts of the lip and palate are sometimes present. Dental problems which are overshadowed by the major syndromic manifestations warrant appropriate management. We have documented an affected South African boy, discussed his dental management and reviewed the oro-dental implications of the disorder.
Asunto(s)
Micrognatismo/etiología , Anomalías Dentarias/etiología , Síndrome de Wolf-Hirschhorn/complicaciones , Niño , Fisura del Paladar/etiología , Caries Dental/cirugía , Humanos , Masculino , Extracción DentalRESUMEN
Members of two generations of a South African family have a unique syndrome comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis. The condition is clinically important as the skin changes, which involve the face, have considerable cosmetic impact, while lung involvement is potentially lethal in adulthood. Skin manifestations which facilitate diagnosis include facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal atrophy. The scalp, facial and body hair are fine and scanty. The tendon contractures lead to progressive digital flexion deformities and abnormalities of the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as progressive dyspnoea. Pedigree data are compatible with an autosomal dominant mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic and fibrous bands and not tendon contractures and is not associated with potentially lethal pulmonary fibrosis. Rather than name this disorder a variant of Weary syndrome, it might be prudent to use as an umbrella title one composed by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis described as inconsistently associated with Weary syndrome) and HSP with tendon/pulmonary involvement (current family) may be classified. The manifestations in this family differ from other poikilodermata and, to the best of our knowledge, have not been previously documented.
Asunto(s)
Contractura/genética , Fibrosis Pulmonar/genética , Síndrome Rothmund-Thomson/genética , Tendones , Adulto , Contractura/patología , Dermatosis Facial/genética , Dermatosis Facial/patología , Femenino , Humanos , Persona de Mediana Edad , Linaje , Fibrosis Pulmonar/patología , Síndrome Rothmund-Thomson/patologíaRESUMEN
AIMS AND OBJECTIVES: Documentation of dental and orthodontic implications of osteoglophonic dysplasia (OGD). SETTINGS AND PARTICIPANTS: Case report describing oral and dental manifestations of a female with OGD, aged 39 years, who was first documented three decades ago. RESULTS: This rare genetic disorder manifests with gross stunting of stature, associated with severe craniofacial malformation and multiple unerupted teeth. Radiographically, multiple lucent lesions were present in the tubular bones and mandible as well as several impacted teeth. CONCLUSION: We concluded that prosthetic dental replacement in this patient would be difficult because of the distorted jaw relationship and large alveolar ridges. Equally, craniofacial reconstruction might be compromised by obstruction of the nasal airways, difficulty in intubation and postoperative respiratory problems.
Asunto(s)
Enfermedades del Desarrollo Óseo/genética , Anomalías Craneofaciales/genética , Enanismo/genética , Rehabilitación Bucal , Ortodoncia Correctiva , Adulto , Femenino , Humanos , Diente Impactado/genética , Diente no Erupcionado/genéticaRESUMEN
The diagnosis of punctate epiphyseal dysplasia (PED) after disappearance of puncta is problematical. In some instances, however, the phenotypic and radiographic characteristics may persist and permit a retrospective diagnosis of PED in persons with unclassified bone dysplasia or bone changes of unknown origin. We report a boy aged 8 years who presented with unusual bony abnormalities that were consistent with a diagnosis of PED.
Asunto(s)
Condrodisplasia Punctata/diagnóstico por imagen , Niño , Diagnóstico Diferencial , Humanos , Masculino , RadiografíaAsunto(s)
Proteoglicanos Tipo Condroitín Sulfato/genética , Cromosomas Humanos Par 15 , Proteínas de la Matriz Extracelular/genética , Lectinas Tipo C/genética , Osteocondrodisplasias/genética , Agrecanos , Ligamiento Genético , Predisposición Genética a la Enfermedad , Humanos , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
The manifestations of the Freeman-Sheldon syndrome (FSS) in four members of a South African family of Xhosa stock have been documented. Orofacial manifestations are a major syndromic component and warrant early, specialized orthodontic intervention. Our protocol for dental management is outlined and suggestions for holistic oro-dental care are provided.
Asunto(s)
Facies , Anomalías Maxilofaciales/terapia , Microstomía/terapia , Adulto , Atención Odontológica , Femenino , Deformidades Congénitas de la Mano/diagnóstico por imagen , Humanos , Lactante , Anomalías Maxilofaciales/diagnóstico por imagen , Planificación de Atención al Paciente , Radiografía , SíndromeRESUMEN
Chondrodysplasia punctata (CDP) was diagnosed clinically and radiographically in a male child born in Cape Town in 1991. His only sibling, a brother born in 2000 was similarly but more severely affected. The boys' mother had longstanding disseminated lupus erythematosus and epilepsy, for which she had been treated with chloraquine and other therapeutic agents during both pregnancies. The parents were non-consanguineous, and the family history was unremarkable. In addition to these affected brothers, seven previous instances of the association of CDP and maternal lupus erythematosus (MLE) have been reported. On this basis, MLE must be regarded as yet another causative factor in CDP.
Asunto(s)
Condrodisplasia Punctata/etiología , Epilepsia/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Complicaciones del Embarazo , Niño , Condrodisplasia Punctata/diagnóstico por imagen , Enfermedad Crónica , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Embarazo , Radiografía , HermanosRESUMEN
Tooth-Nail dysplasia is a rare genetic disorder, which is classified as an ectodermal dysplasia. Diagnostic differentiation from other conditions in this category is necessary for effective dental management and genetic counseling. The oro-dental and clinical manifestations of Tooth-Nail dysplasia in an affected male infant and his father are documented. Other family members have the condition and pedigree data are in keeping with autosomal dominant inheritance. A comprehensive approach to the dental management of an affected child is proposed.
Asunto(s)
Displasia Ectodérmica/complicaciones , Uñas Malformadas/etiología , Anomalías Dentarias/etiología , Anomalías Dentarias/terapia , Adulto , Preescolar , Resinas Compuestas , Restauración Dental Permanente , Humanos , Masculino , Linaje , Síndrome , Diente Primario/anomalíasRESUMEN
Crouzon craniostenosis [MIM 123500], is identified on the basis of the additional phenotypical manifestations of acanthosis nigricans, vertebral changes and cementomas of the jaws. Choanal atresia and hydrocephalus are other features. The molecular defect in CDSS is a point mutation in the FGFR3 gene on chromosome 4p, whereas, the mutation in the Crouzon syndrome is in the FGFR2 gene at 10q25.3-26. An affected girl aged 2 years presented at the UWC dental genetics unit with a prior diagnosis of Crouzon syndrome. Choanal atresia had necessitated a permanent tracheostomy, and hydrocephalus was managed by a shunt operation. Clinical examination revealed acanthosis nigricans in the axilliary regions, a diagnosis confirmed by a biopsy of the lesion. Eruption of the primary dentition was delayed with only six out of twenty teeth present. Radiographic examination conducted shortly after birth revealed the presence of several tooth buds in both the maxillae and the mandible. The delayed eruption of the teeth will be of significance in future orthodontic and maxillofacial measures for the improvement of the patient's facial Crouzonodermoskeletal syndrome (CDSS) was separated from the classical appearance. Molecular investigations in the girl and her parents are underway. If the specific mutation in FGFR3 is observed, a positive diagnosis of CDSS will be confirmed and the status of her parents and other family members will be determined. On this basis, appropriate genetic management can be offered to the kindred.
Asunto(s)
Acantosis Nigricans/patología , Anodoncia/etiología , Cromosomas Humanos Par 4/genética , Disostosis Craneofacial/patología , Facies , Proteínas Tirosina Quinasas , Receptores de Factores de Crecimiento de Fibroblastos/genética , Atresia de las Coanas/etiología , Atresia de las Coanas/cirugía , Disostosis Craneofacial/complicaciones , Disostosis Craneofacial/genética , Disostosis Craneofacial/cirugía , Femenino , Dedos/anomalías , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Recién Nacido , Mutación Puntual , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Retrognatismo , Columna Vertebral/anomalías , SíndromeRESUMEN
Spondyloenchondromatosis (SEM) is a rare skeletal dysplasia which presents with multiple enchondromata in the metaphyses of the long bones associated with dysplastic vertebral bodies. It is probably heterogeneous. We have investigated and documented a male infant in South Africa with spondyloenchondromatosis and persistent D-2-hydroxyglutaric aciduria (D2HA). D2HA is a neurometabolic disorder whose enzymatic basis is still undefined. A girl in England with a similar clinical, radiological and biochemical phenotype has previously been reported by Talkhani et al. [(2000). Skel Radiol 7:215-2921]. There is at present a lack of a plausible pathogenetic relationship between the two components of the disorder but a contiguous gene syndrome or a pleiotropic gene could be considered. Whatever the underlying mechanism this case report confirms its nosological entity.
Asunto(s)
Brazo/anomalías , Encondromatosis/fisiopatología , Glutaratos/metabolismo , Pierna/anomalías , Brazo/diagnóstico por imagen , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Glutaratos/orina , Humanos , Lactante , Pierna/diagnóstico por imagen , Vértebras Lumbares/anomalías , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Radiografía , Escápula/anomalías , Escápula/diagnóstico por imagenRESUMEN
Sclerosteosis (SCL) is a severe, progressive, autosomal-recessive craniotubular hyperostosis (MIM 269500). The determinant gene (SOST) has been isolated, and genotype-phenotype correlations, as well as the elucidation of pathogenetic mechanisms, are dependent upon the documentation of the natural history of the condition. For this reason, the course and complications in 63 affected individuals in South Africa, seen over a 38-year period, have been analyzed. Thirty-four of these persons died during the course of the survey, 24 from complications related to elevation of intracranial pressure as a result of calvarial overgrowth. The mean age of death in this group of individuals was 33 years, with an even gender distribution. Facial palsy and deafness, as a result of cranial nerve entrapment, developed in childhood in 52 (82%) affected persons. Mandibular overgrowth was present in 46 (73%) adults and syndactyly in 48 (76%). In South Africa in 2002, 29 affected persons were alive, 10 being < or =20 years of age. It is evident that sclerosteosis is a severe disorder which places a considerable burden upon affected individuals and their families.
Asunto(s)
Anomalías Múltiples/genética , Hiperostosis/genética , Proteínas Adaptadoras Transductoras de Señales , Proteínas Morfogenéticas Óseas/genética , Cromosomas Humanos Par 17/genética , Enfermedades del Nervio Facial/genética , Femenino , Dedos/anomalías , Marcadores Genéticos/genética , Pérdida Auditiva/genética , Humanos , Hiperostosis/epidemiología , Presión Intracraneal/genética , Anomalías Maxilomandibulares , Masculino , Síndromes de Compresión Nerviosa/genética , Sudáfrica/epidemiología , Sindactilia/genéticaRESUMEN
A boy with the Schwartz-Jampel syndrome (chondrodystrophic myotonia) had a number of oro-dental complications. These included difficulty in tooth extraction and orthodontic care due to a small oral aperture and rigidity of the temporo-mandibular joints. General anaesthesia was hazardous because of a propensity to malignant hyperthermia, and endotracheal intubation was difficult because of shortness and rigidity of the neck and the small size of the laryngeal structures. Awareness of these potential problems is crucial for anaesthesia and comprehensive dental management. The radiological demonstration of dentigerous cysts is a hitherto unreported observation in this disorder.