RESUMEN
Five subjects with mucopolysaccharidosis type I and symptomatic cervical spinal stenosis received intrathecal laronidase in a 4-month pilot study and/or a 12-month extension study [1]. Clinical descriptions of study subjects, nonserious adverse events, individual data tables, and scoring system methods are provided. There were ten nonserious adverse events that occurred in more than one study subject. Somatosensory evoked potentials were absent in two subjects and normal in two subjects, limiting their utility as an endpoint. There were no significant changes in magnetic resonance imaging of cervical spinal cord or brain, pulmonary function tests, or cerebrospinal fluid opening pressure. These data are presented along with the scoring methods used in evaluation of the study subjects.
Asunto(s)
Anemia Aplásica/genética , Enanismo/genética , Endorribonucleasas/genética , Síndromes de Inmunodeficiencia/genética , Mutación , Anemia Aplásica/diagnóstico , Enanismo/diagnóstico , Enanismo/diagnóstico por imagen , Femenino , Fémur/anomalías , Predisposición Genética a la Enfermedad , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/patología , Lactante , Deformidades Congénitas de las Extremidades Inferiores/diagnóstico , Ganglios Linfáticos/patología , Osteocondrodisplasias/diagnóstico , Radiografía , Síndrome , Timo/patologíaRESUMEN
Progressive hearing loss is a major symptom in osteogenesis imperfecta (OI), a genetic brittle bone disease. Vertigo is frequently associated with otosclerosis in which the hearing loss clinically resembles that in OI. Vertigo is also common in basilar impression (BI) found in up to 25% of adult OI patients. In order to evaluate the cause, frequency, and characteristics of vertigo in OI, 42 patients were studied by interview, clinical examination, and audiological examination supplemented with electronystagmography (ENG) and lateral skull radiography. Audiometry showed hearing loss in 25 patients (59.5%). Nine patients (21%) displayed abnormal skull base anatomy in the forms of basilar impression, basilar invagination, or both, all designated here as BI. Twenty-two patients (52.4%) reported vertigo, mostly of floating or rotational sensation of short duration. Patients with hearing loss tended to have more vertigo than patients with normal hearing. Vertigo was not correlated with type of hearing loss or auditory brain-stem response (ABR) pathology. ENG was abnormal in 14 patients (33.3%). No dependency was found between vertigo and deviant ENG results. Patients with BI tended to have more vertigo than patients with normal skull base but the difference was not statistically significant. Neither ENG pathology, nor the presence or type of hearing loss showed correlation with BI. In conclusion, vertigo is common in patients with OI. In most cases, it may be secondary to inner ear pathology, and in only some patients does BI explain it. Since some OI patients without BI or hearing loss also suffer from vertigo, further clinical and neurological studies are needed to define the pathogenesis of vertigo in OI.
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Osteogénesis Imperfecta/fisiopatología , Enfermedades Vestibulares/fisiopatología , Adulto , Femenino , Pérdida Auditiva/fisiopatología , Humanos , Masculino , Osteogénesis Imperfecta/complicaciones , Vértigo/fisiopatología , Enfermedades Vestibulares/complicacionesRESUMEN
OBJECTIVE: It has been firmly established that mutations in the gene for fibrillin 1, FBN1, cause Marfan syndrome (MFS). FBN1 mutations can also cause other phenotypes, such as ectopia lentis (EL) and familial isolated thoracic aortic aneurysm and dissection (FAA). When the clinical presentation is typical, diagnosis of MFS is usually easy to make. However, there can be a marked phenotypic variation between affected subjects even in one family, and making the diagnosis can be challenging, especially in childhood. The objective of this study was to test the sensitivity of conformation sensitive gel electrophoresis (CSGE) for detecting mutations in FBN1 in MFS and related phenotypes. DESIGN: Setting up CSGE analysis for the FBN1 gene and testing the method first by screening coded samples from 17 MFS patients with previously detected FBN1 mutations. We then used a test set consisting of 46 coded samples representing MFS, related phenotypes, and controls. RESULTS: Sixteen of the 17 known mutations were detected. Altogether 23 mutations were detected in a test set consisting of 46 coded samples representing MFS, related phenotypes, and controls. Nineteen of the mutations were novel. The mutation was detected in 18 of the 20 MFS patients and in one patient with familial EL, but not in a patient with sporadic MASS syndrome, any of the five sporadic annuloaortic ectasia (AAE) patients, or any of the 15 controls. A FBN1 mutation was detected in four members of a multigeneration family with AAE, however. CONCLUSIONS: These results indicate that CSGE is highly sensitive for the detection of mutations in FBN1, and that molecular diagnostics is a useful means of confirming clinical diagnoses of MFS and related disorders. Further careful investigations are needed, however, in order to correlate the interfamilial and intrafamilial clinical variabilities of fibrillinopathies and mutations in FBN1.
Asunto(s)
Electroforesis en Gel de Poliacrilamida , Síndrome de Marfan/genética , Mutación/genética , Adolescente , Adulto , Anciano , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/genética , Niño , Análisis Mutacional de ADN/métodos , Diagnóstico Diferencial , Desplazamiento del Cristalino/diagnóstico , Desplazamiento del Cristalino/genética , Electroforesis en Gel de Poliacrilamida/métodos , Proteínas de la Matriz Extracelular/genética , Femenino , Fibrilina-1 , Fibrilinas , Humanos , Masculino , Síndrome de Marfan/diagnóstico , Proteínas de Microfilamentos/genética , Persona de Mediana Edad , Polimorfismo Conformacional Retorcido-Simple , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
We describe 3 siblings with asphyxiating thoracic dysplasia whose neonatal symptoms range from mild respiratory distress to asphyxia and death. The youngest sibling received aggressive modern respiratory intensive care, survived, and at 2 years showed no respiratory symptoms. Improved neonatal intensive care has implications for clinical decision making and genetic counseling.
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Asfixia Neonatal/genética , Asfixia Neonatal/terapia , Tórax/anomalías , Femenino , Genes Recesivos , Humanos , Recién Nacido , Cuidado Intensivo Neonatal , Masculino , Osteocondrodisplasias/genética , Osteocondrodisplasias/terapia , Pronóstico , Terapia Respiratoria , SíndromeRESUMEN
Cartilage-hair hypoplasia is a chondrodysplasia with a high incidence of Hirschsprung disease. This study suggests that Hirschsprung disease is associated especially with severe cartilage-hair hypoplasia: the patients with Hirschsprung disease had severe growth failure and a higher incidence of alopecia, infections, malignancies, and childhood anemia than the patients with cartilage-hair hypoplasia who did not have Hirschsprung disease.
Asunto(s)
Exostosis Múltiple Hereditaria/complicaciones , Cabello/anomalías , Enfermedad de Hirschsprung/complicaciones , Femenino , Crecimiento , Enfermedad de Hirschsprung/fisiopatología , Humanos , Recién Nacido , MasculinoRESUMEN
CONTEXT: Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD. OBJECTIVE: To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD. DESIGN AND SETTING: Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland. PARTICIPANTS: A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias). MAIN OUTCOME MEASURES: Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD. RESULTS: Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103-->Trp (arginine-->tryptophan) substitution in the alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326-->Trp (glutamine-->tryptophan) substitution in the alpha2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P =.000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold. CONCLUSION: This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.
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Colágeno Tipo IX , Colágeno/genética , Desplazamiento del Disco Intervertebral/genética , Triptófano/genética , Adulto , Anciano , Alelos , Arginina , Estudios de Casos y Controles , Análisis Mutacional de ADN , Electroforesis , Finlandia , Predisposición Genética a la Enfermedad , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico , Vértebras Lumbares , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mutación Puntual , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
The recessively inherited developmental disorder, cartilage-hair hypoplasia (CHH) is highly pleiotropic with manifestations including short stature, defective cellular immunity, and predisposition to several cancers. The endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins. It has at least two functions, namely, cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA. We describe numerous mutations in the untranslated RMRP gene that cosegregate with the CHH phenotype. Insertion mutations immediately upstream of the coding sequence silence transcription while mutations in the transcribed region do not. The association of protein subunits with RNA appears unaltered. We conclude that mutations in RMRP cause CHH by disrupting a function of RNase MRP RNA that affects multiple organ systems.
Asunto(s)
Cartílago/anomalías , Endorribonucleasas/genética , Cabello/anomalías , Osteocondrodisplasias/genética , ARN/genética , Alelos , Secuencia de Bases , Mapeo Cromosómico , Análisis Mutacional de ADN , Endorribonucleasas/metabolismo , Silenciador del Gen , Marcadores Genéticos , Humanos , Datos de Secuencia Molecular , Mutación , Osteocondrodisplasias/metabolismo , Pruebas de Precipitina , Regiones Promotoras Genéticas , ARN/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismoRESUMEN
BACKGROUND: Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia with severe growth failure and impaired immunity. Impaired immunity may result in increased mortality. AIMS: To follow a cohort of 120 CHH patients for mortality from 1971 to 1995. METHODS: The overall and cause specific disease mortality rates in patients with CHH, and the disease mortality rate in 194 parents and 158 non-affected sibs were compared with the national rates. RESULTS: During follow up seven disease related deaths were observed versus 0.8 expected (standardised mortality ratio 9.3, 95% confidence interval 3.7 to 19). In most cases, the deaths were confined to the younger age groups and associated with defective immunity. The mortality of the parents and the non-affected sibs was similar to that in the general population. CONCLUSION: The study confirms increased mortality in patients with CHH attributable to defective immunity, especially in children.
Asunto(s)
Cabello/anomalías , Osteocondrodisplasias/mortalidad , Adolescente , Adulto , Niño , Preescolar , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Heterocigoto , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/mortalidad , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/genética , Tasa de SupervivenciaAsunto(s)
Osteomalacia/diagnóstico , Raquitismo/diagnóstico , Deficiencia de Vitamina D/prevención & control , Adulto , Niño , Finlandia/epidemiología , Humanos , Hipofosfatemia/diagnóstico , Hipofosfatemia/epidemiología , Osteomalacia/epidemiología , Osteomalacia/etiología , Raquitismo/epidemiología , Raquitismo/etiología , Vitamina D/metabolismo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiologíaAsunto(s)
Colágeno Tipo I/genética , Osteogénesis Imperfecta , Colágeno/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Continuidad de la Atención al Paciente , Difosfonatos/uso terapéutico , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Genes Dominantes , Humanos , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/terapia , LinajeRESUMEN
We report follow-up from birth up to 16 years of age of a patient with a previously undescribed combination of dysmorphic features. These include: intrauterine growth retardation developing to normal adult stature with truncal obesity, asymmetry of the midface skeleton with severe orthodontic problems, brachydactyly of the hands and feet, wide medial phalanges of the fingers, partial soft tissue syndactyly, simian creases and normal mental development. We consider other differential diagnoses and suggest that the patient represents a hitherto undescribed syndrome.
Asunto(s)
Anomalías Múltiples/patología , Huesos/anomalías , Discapacidades del Desarrollo/patología , Cara/anomalías , Obesidad/patología , Adolescente , Preescolar , Humanos , Lactante , Recién Nacido , Masculino , SíndromeRESUMEN
OBJECTIVE: Cartilage-hair hypoplasia (CHH), a metaphyseal chondrodysplasia, is usually associated with impaired cellular immunity. This study evaluates humoral immunity in patients with CHH. METHODS: The concentrations of immunoglobulins G, A, and M (IgG, IgA, and IgM) and IgG subclasses were studied in 20 patients. Data for 5 additional patients with recurrent infections were retrospectively reviewed. RESULTS: Seven of the prospectively evaluated patients (35%) had defective humoral immunity. Three patients had IgA deficiency. Four patients had IgG2 deficiency, accompanied by IgA deficiency, IgG4 deficiency, or both in 3 patients. IgG4 was low in most patients. Increased infections were usually associated with supranormal IgG and IgG1 and subnormal IgA, IgG2, or IgG4 concentrations. One retrospectively reviewed patient had severe hypogammaglobulinemia, and 3 had multiple IgG subclass deficiencies. CONCLUSIONS: Humoral immunity is impaired in CHH and contributes to the increased susceptibility to infections.
Asunto(s)
Enfermedades de los Cartílagos/inmunología , Enfermedades del Cabello/inmunología , Deficiencia de IgA/complicaciones , Deficiencia de IgG/complicaciones , Inmunoglobulina M/deficiencia , Adolescente , Enfermedades de los Cartílagos/sangre , Niño , Preescolar , Enfermedades del Cabello/sangre , Humanos , Deficiencia de IgA/sangre , Deficiencia de IgG/sangre , Inmunoglobulina M/sangre , Lactante , Infecciones/epidemiología , Infecciones/inmunología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
UNLABELLED: Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue. Progressive hearing loss is one of the principal symptoms of OI, affecting about 50% of adult patients. Hearing loss may also occur in childhood and results in additional disability in education and psychosocial adaptation and aggravates the physical handicap. This can be avoided by appropriate otological and audiological treatment. In a nationwide search, 254 Finnish patients with OI were identified indicating a prevalence of 4.9/100,000. Of the 60 children, 45 aged between 4 and 16 years accepting to participate the study on hearing, were evaluated by a questionnaire and clinical audiometry. Hearing loss was defined as pure tone average (PTA0.5-2 kHz) more than 20 dB hearing level (HL). A clinical geneticist determined the type of OI among the 45 patients. Two sporadic OI cases with conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV OI with a PTA0.5-2 kHz of 35/40 dB HL and a 15-year-old boy with type IV OI with a PTA0.5-2 kHz of 27/18 dB HL. In addition, a 6-year-old girl with familial OI type I had either a congenital sensorineural deafness or early progressive deafness with PTA0.5-2 kHz of 97/103 dB HL, probably of unrelated aetiology. CONCLUSION: Hearing loss in children with osteogenesis imperfecta is less frequent than generally suspected. Nevertheless, it is recommended that audiometry is performed in children with osteogenesis imperfecta even without symptoms of hearing loss at the age of 10 years, and repeated every 3 years thereafter.
Asunto(s)
Pérdida Auditiva Conductiva/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Osteogénesis Imperfecta/diagnóstico , Adolescente , Adulto , Audiometría de Tonos Puros , Umbral Auditivo , Niño , Preescolar , Sordera/diagnóstico , Sordera/genética , Femenino , Finlandia , Pérdida Auditiva Conductiva/genética , Pérdida Auditiva Sensorineural/genética , Humanos , Masculino , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/genéticaRESUMEN
We have carried out a mutation screening of the PHEX gene in Finnish patients with hypophosphatemia. A total of 100% (5/5) of the familial HYP patients (X-linked hypophosphatemia) and 93% (14/15) of the sporadic cases were found to carry a mutation in the PHEX gene. We identified 18 mutations, of which 15 were novel. We report also a new polymorphism 46bp upstream of exon 16. Two families were segregating the same nonsense mutation in exon 1 (R20X), but since this mutation has been previously reported in three independent studies, we consider it to be a mutational hotspot rather than a Finnish founder mutation. We did not find PHEX gene mutations in two additional hypophosphatemia families in which the mode of inheritance was other than X-linked dominant. Also, no mutation could be detected in a patient with suspected oncogenic osteomalacia (OHO).
Asunto(s)
Hipofosfatemia Familiar/genética , Mutación/genética , Proteínas/genética , Niño , Análisis Mutacional de ADN , Femenino , Finlandia , Pruebas Genéticas , Homocigoto , Humanos , Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia Familiar/diagnóstico por imagen , Hipofosfatemia Familiar/tratamiento farmacológico , Masculino , Mutación Missense/genética , Osteomalacia/genética , Endopeptidasa Neutra Reguladora de Fosfato PHEX , Polimorfismo Genético/genética , Radiografía , Resultado del TratamientoRESUMEN
UNLABELLED: Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive spondylo-epiphyseal dysplasia. The characteristic features of SIOD include 1) short stature with hyperpigmented macules and an unusual facies, 2) proteinuria with progressive renal failure, 3) lymphopenia with recurrent infections, and 4) cerebral ischaemia. Although 25 patients have been reported with this disorder, the clinical course and phenotype of SIOD are not well characterized. This report summarizes the clinical findings, course and treatment of reported patients and includes 14 additional patients with SIOD. We emphasize the high incidence of cerebral ischaemia and ocular abnormalities, define the high incidence of thyroid dysfunction and blood cytopenia, and confirm the absence of effective and durable medical therapies. CONCLUSION: Schimke immuno-osseous dysplasia is a multi-system autosomal recessive disorder with variable expression that affects the skeletal, renal, immune, vascular, and haematopoietic systems. Medical therapy is limited especially for more severely affected individuals.
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Osteocondrodisplasias/diagnóstico , Adolescente , Enfermedades Autoinmunes/etiología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Osteocondrodisplasias/inmunología , Osteocondrodisplasias/terapia , SíndromeRESUMEN
Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia characterized by severe short-limbed short stature, hypoplastic hair, and defective immunity. The patients also have anemia. As GH may regulate both body growth and erythropoiesis, we used CHH as a clinical model to study their interrelationships. Retrospective analysis of hematological data of 114 patients showed that the severity of the anemia and macrocytosis in CHH varies with age. The anemia was most severe in early childhood. A prospective study of 21 patients with CHH showed that height correlates with hemoglobin (P = 0.006) and mean corpuscular volume of red blood cells (P < 0.0001). The individual hemoglobin levels correlated with the GH parameters [P = 0.035 for insulin-like growth factor I (IGF-I) and P = 0.002 for IGF-binding protein-3], and the mean corpuscular volume of red blood cell values correlated with fetal hemoglobin. Bone marrow cultures obtained from six patients with CHH showed reduced or totally absent erythroid colony formation, which was not influenced by GH or IGF-I in vitro or by GH treatment in vivo. In patients with CHH, we observed an association between erythropoiesis and growth. We conclude that body growth and erythropoiesis share common regulators. One of these is the GH-IGF-I axis; other factors, as not yet identified, may also be important.
Asunto(s)
Anemia/etiología , Cartílago/patología , Exostosis Múltiple Hereditaria/complicaciones , Exostosis Múltiple Hereditaria/patología , Cabello/patología , Adolescente , Anemia/sangre , Estatura , Médula Ósea/patología , Niño , Preescolar , Volumen de Eritrocitos , Eritropoyesis , Exostosis Múltiple Hereditaria/sangre , Exostosis Múltiple Hereditaria/fisiopatología , Femenino , Crecimiento , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
Cabello/anomalías , Síndromes de Inmunodeficiencia/inmunología , Osteocondrodisplasias/complicaciones , Adolescente , Adulto , Formación de Anticuerpos , Niño , Preescolar , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Inmunidad Celular , Inmunoglobulina G/sangre , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/mortalidad , Lactante , Recién Nacido , Persona de Mediana Edad , Osteocondrodisplasias/inmunología , Osteocondrodisplasias/mortalidad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed.
Asunto(s)
Neoplasias Óseas/genética , Condrosarcoma/genética , Exostosis Múltiple Hereditaria/genética , Adolescente , Adulto , Anciano , Neoplasias Óseas/cirugía , Huesos/patología , Transformación Celular Neoplásica/genética , Condrosarcoma/cirugía , Cromosomas Humanos Par 11 , Exostosis Múltiple Hereditaria/cirugía , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , LinajeRESUMEN
STUDY DESIGN: An evaluation of cervical kyphosis in diastrophic dysplasia from newborn to adult life. OBJECTIVES: To discover the prevalence and natural history of cervical kyphosis in diastrophic dysplasia. SUMMARY OF BACKGROUND DATA: Typical findings in this rare skeletal dysplasia are sport-limbed short stature, multiple joint contractures, early degeneration of joints, and spinal deformities such as cervical kyphosis, scoliosis, and exaggerated lumbar lordosis. In diastrophic dysplasia, spontaneous resolution of cervical kyphosis has been reported, but so have severe forms causing medullar compression leading to quadriplegia and death. The prevalence and clinical outcome of the kyphosis are not known. METHODS: The radiographic natural history of the cervical spine was studied in 120 patients. They varied in age from newborns to 63-year-olds. The average follow-up time in 26 living patients with cervical kyphosis was 10.0 years. RESULTS: Midcervical kyphosis was noted in 29 patients (24%) in their first radiograph. In 25 patients, the first radiographs were taken before the age of 18 months, and 24 of these patients (96%) had cervical kyphosis. The most severe case was that of a 32-year-old patient with a 165 degrees kyphosis. In the 24 patients, the kyphosis resolved spontaneously at an average age of 7.1 years. Three patients with a severe kyphosis died; one patient is alive. One patient, a 4-year-old child has mild resolving deformity. CONCLUSIONS: Cervical kyphosis in diastrophic dysplasia usually is shown at the time of birth. It resolves spontaneously during growth and seldom needs treatment. Careful follow-up study and treatment, if necessary, are important tools for avoiding the neurologic problems and fatal outcome.