RESUMO
We describe five patients from three different families with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), which was molecularly confirmed by homozygosity for the g.51G >A and g.55G >A mutations in RNU4ATAC, respectively. The patients showed the classical phenotype and demonstrated in addition variable degrees of gyration abnormalities and malformations of the callosal body with an interhemispheric cyst. One patient also showed underdevelopment of the cerebellar vermis. This confirms that cortical malformations should be considered cardinal manifestations of MOPD I. Oculocutaneous albinism, brain hemorrhage and chilblains have been found to be associated with MOPD I. The present study showed lack of retinal pigmentation in three patients of whom two had an unusually fair complexion of hair and skin. One patient was found to have a hematoma in the left thalamus. This may indicate that both pigmentary abnormalities and vascular anomalies may be part of the phenotype of MOPD I as well.
Assuntos
Anormalidades Múltiplas/genética , Corpo Caloso/patologia , Nanismo/genética , Retardo do Crescimento Fetal/genética , Hematoma/genética , Microcefalia/genética , Mutação/genética , Osteocondrodisplasias/genética , Transtornos da Pigmentação/genética , Ribonucleoproteínas Nucleolares Pequenas/genética , Doenças Talâmicas/genética , Adulto , Nanismo/patologia , Feminino , Retardo do Crescimento Fetal/patologia , Hematoma/patologia , Humanos , Recém-Nascido , Masculino , Microcefalia/patologia , Osteocondrodisplasias/patologia , Fenótipo , Transtornos da Pigmentação/patologia , Doenças Talâmicas/patologia , Adulto JovemRESUMO
The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I.
Assuntos
Nanismo/genética , Retardo do Crescimento Fetal/genética , Microcefalia/genética , Mutação , Osteocondrodisplasias/genética , Transtornos da Pigmentação/genética , Adolescente , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/patologia , Pré-Escolar , Consanguinidade , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Nanismo/patologia , Feminino , Retardo do Crescimento Fetal/patologia , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/patologia , Osteocondrodisplasias/patologia , Linhagem , Exame Físico , Transtornos da Pigmentação/patologia , Gravidez , Terceiro Trimestre da Gravidez , RNA Nuclear Pequeno/análise , IrmãosRESUMO
Oto-spondylo-megaepiphyseal dysplasia (OSMED) is a very rare disorder due to mutation of type XI collagen. Less than 30 patients have been reported in the literature so far. It could be either of autosomal dominant (OMIM 154780) or recessive (OMIM 215150) etiology. Two sibs with OSMED are presented. They had disproportionate short stature and short limbs, distinct face with midface hypoplasia, short nose, depressed nasal bridge, long philtrum, and non-progressive sensorineural deafness. Radiological findings showed short long bones and large epiphyses with metaphyseal flaring and mild platyspondyly and coronal clefting. Homozygosity of a single nucleotide deletion in exon 55 causing a premature stop codon in exon 56 of COL11A2 was detected in the affected sibs. Parents were heterozygotes for the same mutation and interestingly, the father had mild unilateral non-progressive sensorineural deafness. This finding adds more weight that the type of mutation and location in COL11A2 are crucial in determining the phenotype. The purpose of this study is to report clinical and radiological findings in two molecularly proven Egyptian sibs with autosomal recessive OSMED.