Microspherophakia-metaphyseal dysplasia: a ''new'' dominantly inherited bone dysplasia with severe eye involvement.

We report a father and son affected by a hitherto unpublished bone dysplasia with moderately severe dwarfism. On initial radiographs, thickening of the diaphyses of the long bones was striking. The small bones of the extremities were almost unaffected. With age, the metaphyseal deformation became more prominent. The epiphyses became irregular and their growth was delayed (particularly the femoral heads). The femoral neck showed an unusual 'lip' on the inner edge. Later, the stubby appearance of the long bones faded and, in adulthood, only enlarged metaphyses and deformed femoral necks persisted. The vertebrae showed moderate deformation with irregular flattening, and narrowing of the spinal canal with a shortened interpedicular distance. The eye defects consisted of high grade myopia, microspherophakia, lens coloboma, lens luxation, and retinal detachment. The name 'microspherophakia-metaphyseal dysplasia' is suggested for this probably autosomal dominant bone dysplasia.     

Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes

A 56-year-old Japanese woman with mandibuloacral dysplasia and type A lipodystrophy is described. Mutation analysis identified a homozygous missense mutation (1585G > A) in exon 9 of the LMNA gene that replaces well-conserved residue alanine at position 529 to threonine (A529T). The woman showed, in addition to the usual clinical manifestations of the disorder, severe progressive skeletal changes: osteoporotic changes with multiple fractures; osteolysis of the right radius; and destructive changes of the vertebrae, leading to compression of the cervical spinal cord and paraplegia. Laboratory findings included markedly reduced bone mineral density; significantly increased urine N-telopeptide of collagen type I, an osteoclast marker; and normal serum bone specific alkaline phosphatase, an osteoblast marker. Regular follow up of adult patients with the disorder is desirable, including skeletal radiography, estimates of bone mineral density, and biochemical markers of bone turnover. Treatment with bisphosphonates to inhibit osteoclast activity is likely to be beneficial.     

髋关节发育不良髋臼骨囊性变的特征

目的观察髋关节发育不良（DDH）继发骨性关节炎时髋臼骨囊性变的位置和大小,为全髋关节置换术（THR）中髋臼重建提供参考。方法回顾性分析2007年6月—2008年11月我院行THR的DDH患者的临床资料,共38例（45髋）;以同期行THR的38例（45髋）原发性髋关节骨性关节炎作为对照组,在髋关节正位x线片和螺旋CT扫描片上观察髋臼骨囊性变的位置,测量骨囊性变的大小。结果DDH组髋关节正位片发现16侧髋臼存在骨囊性变,螺旋CT扫描片发现21侧髋臼存在骨囊性变,髋臼冠状面测定囊变面积为（4．7±5．1）mm2。对照组髋关节正位片发现6侧髋臼存在骨囊性变,螺旋CT片发现10侧髋臼存在骨囊性变,囊变区面积为（1．3±2．4）mm2,两组间骨囊性变的发生率和面积差异均有统计学意义（P值均〈0．05）。结论DDH继发骨性关节炎的髋臼存在高发的骨囊性变。在THR髋臼重建过程中应对其进行刮除植骨,否则可能影响到髋臼假体的稳定性。     

Association of kyphomelic dysplasia with severe combined immunodeficiency

Kyphomelic dysplasia is a distinct, rare, skeletal dysplasia with short angulated femora, bowing of long bones, short ribs, narrow thorax, and metaphyseal abnormalities. While immune deficiency occurs in other short stature/short-limb skeletal dysplasias and cartilage-hair hypoplasia, it has not been described with kyphomelic dysplasia. We report on an infant with this disorder who had profound humoral and cellular immunologic abnormalities consistent with severe combined immune deficiency (SCID). The infant died at age 2 months of overwhelming cytomegalovirus pneumonia. Kyphomelic dysplasia, as with other short stature/short-limb skeletal dysplasias, can be associated with immune deficiency and immune function should be investigated when this disorder is identified. © 1995 Wiley-Liss, Inc.     

Osseous dysplasia with severe short stature, multiple dislocations, and delayed bone age: report on a second Lebanese patient

We describe a young girl with severe pre- and postnatal short stature, bilateral dislocation of hips, knees and elbows, and right clubfoot. Skeletal investigations disclosed an anisospondyly, the absence of ossification of the odontoid apophysis and of fusion of the neural arches of the cervical vertebrae, abnormal L3 and L4 vertebrae, partial agenesis of the coccyx, abnormal and sub-luxated radial heads, bilateral dislocation of the hips, dysplastic acetabulae, pseudoacetabulae, hypoplasia of the femoral heads, short femoral necks, short long bones with thin diaphyses, widening of the medullary canal and thinning of the cortical one, slightly enlarged metaphyses, and diffuse osseous demineralization. Bone age was delayed. The girl's parents are first cousins. Differential diagnoses are discussed and the possibility is raised that this might be a second patient with clinical features indicating an entity recently described in a young Lebanese boy [Mégarbané and Ghanem (2004); Am J Med Genet Part A 130A: 107-109]. A clinical follow-up of the latter patient is also reported.     

SARS尸检组织的病理变化和超微结构观察

目的 研究严重急性呼吸综合征(SARS)尸检组织的临床病理和超微结构特征。方法 对1例SARS死亡患者做即刻肺穿刺和12h后尸检,进行病理形态和超微结构的观察;用Macchiavello法做病毒包涵体染色;并对淋巴结、脾脏、结肠、小肠及骨髓组织行CD20、CD45RO(UCHL-1)、CD4、CD8、CD68、CD34免疫组织化学标记。结果 SARS肺的主要病变为急性弥漫性全小叶性间质性炎,可见肺泡腔内透明膜形成和增生及脱落的肺泡上皮,偶见胞质内病毒包涵体样结构,病毒包涵体染色阳性,肺内小血管增生、扩张,呈血管炎性改变。淋巴结、脾脏结构破坏,淋巴滤泡消失,脾小体萎缩,淋巴细胞明显减少,组织细胞增生;结肠、小肠孤立和集合淋巴结淋巴滤泡消失;骨髓增生减低,巨核细胞增多。免疫组织化学染色：淋巴结、脾脏B细胞CD20弥漫散在阳性,CD45RO(UCHL-1)散在阳性,CD4辅助T细胞显著减少,CD8毒性T细胞稍增加,CD4／CD8比例明显小于0．5。电镜观察：肺泡内的单核巨噬细胞、肺泡上皮胞质内可见病毒样颗粒,大小80～160nm,有光晕或花环状包膜。结论 肺部明显急性弥漫性全小叶性间质性炎,肺泡腔透明膜形成,肺外淋巴造血系统明显损害,尤T细胞明显;内脏器官出血、坏死和血管炎改变等为急性SARS的形态特征;肺内所见病毒样颗粒可能为新型冠状病毒,推测其为此次SARS流行的主要病原体。     

Polyostotic fibrous dysplasia with cranial hyperostosis: new entity or most severe form of polyostotic fibrous dysplasia?

Polyostotic fibrous (McCune-Albright) dysplasia is an uncommon nonhereditable disorder characterized by localized or widespread cystic changes in the skeleton. The limb bones are predominantly affected; craniofacial involvement is rare. We have encountered a severely affected man, with the additional manifestation of massive craniofacial hyperostosis. It is questionable whether this condition is an autonomous entity or represents the end of the spectrum of severity of polyostotic fibrous dysplasia.     

Costovertebral dysplasia in a patient with partial trisomy 22

A newborn female presented with costovertebral dysplasia (CVD), subtle facial anomalies, and neonatal respiratory distress. Her karyotype demonstrated a small supernumerary NOR-positive marker that was subsequently identified as del(22)(q11.2). This extra structurally abnormal chromosome was found by DNA microsatellite marker analyses to be derived from a paternal chromosome 22. The child has had severe growth and developmental delay along with pulmonary insufficiency and hypoxia but is presently stable at age 20 months. Findings in our patient correlate with similar observations in children with small markers derived from D/G and D/D translocations reported before banding technology was available. These reports and recent mapping results suggest that a pericentric gene family, distributed on one or more acrocentric chromosomes, may have played a role in the development of the human axial skeleton. Data from additional studies will be needed to confirm or refute this hypothesis.     

A boy with severe craniodiaphyseal dysplasia and apparently normal mother

We describe a boy and his mother affected with craniodiaphyseal dysplasia (CDD). The boy had a very severe form of the disease with extensive osteosclerosis already at birth. Facial diplegia, bilateral hearing loss and optic nerve atrophy were early, severe complications of the disease. At age 7 years progressive genu valgum and unusual epimetaphyseal radiographic appearances suggested hyperparathyroidism. This was confirmed by biochemical tests. Because of some facial similarity between the asymptomatic mother and the propositus, a limited skeletal survey of the mother was performed. It demonstrated cranial osteosclerosis and hyperostosis. It is possible that the mother has somatic mosaicism for a mutation of the genes causing CDD.     

Craniotubular dysplasia with severe postnatal growth retardation,mental retardation,ectodermal dysplasia,and loose skin: Lenz-Majewski-Like syndrome

The heterogeneous group of craniotubular dysplasias is characterized by modeling errors of the craniofacial and tubular bones. Some conditions in this category cause not only skeletal abnormalities but also a variety of mesoectodermal dysplasias, as exemplified in Lenz-Majewski syndrome (MIM 151050), which comprises craniodiaphyseal dysplasia, failure to thrive, mental retardation, proximal symphalangism, enamel hypoplasia, and loose skin. We report on a boy with a hitherto unknown multisystem disorder, including skeletal changes that were regarded as a form of craniotubular dysplasia. The patient had a large head, exophthalmos, a broad nasal root, anteverted nostrils, large auricles, thick lips, micrognathia, severe postnatal growth retardation with emaciation, severe mental retardation, sparse hair growth, enamel hypoplasia, and thin, loose skin with hyperlaxity. Skeletal changes consisted of thickened calvaria, sclerosis of the skull base and facial bones, thick ribs, and metaphyseal undermodeling of the tubular bones. In addition, generalized osteopenia was evident. The present disorder overlaps phenotypically with Lenz-Majewski syndrome; nevertheless, the absence of diaphyseal hyperostosis and proximal symphalangism in the present patient was not consistent with Lenz-Majewski syndrome. Am. J. Med. Genet. 71:87–92, 1997. © 1997 Wiley-Liss, Inc.     

Novel TBXAS1 variants in two Indian children with Ghosal hematodiaphyseal dysplasia: A concise report

Ghosal hematodiaphyseal dysplasia (GHDD) is a rare, autosomal recessive condition characterised by diaphyseal dysplasia of long bones with defective haematopoiesis. We describe 2 such cases with clinical and radiological evidence of GHDD. Molecular analysis revealed novel variants in TBXAS1 gene in both of them. Suspicion and confirmation of this entity is crucial in cases of refractory anemia with bony deformities, as the clinical manifestations in this entity are usually well responsive to corticosteroids.     

Progressive cognitive decline in an adult patient with cleidocranial dysplasia

Cleidocranial dysplasia is a skeletal disorder characterized by a defective skull and defective clavicles caused by RUNX2, an activator of osteoblast differentiation. Consistent with the expression pattern of RUNX2, this disorder typically affects the skeletal system, but not the central nervous system. A 56-year-old man with the prototypic skeletal defects of cleidocranial dysplasia and a RUNX2 deletion presented with a progressive cognitive decline after the age of 40 years. After a failed cranioplasty during childhood, he had worn a protective helmet until young adulthood. His current neuroimaging studies revealed extensive cystic encephalomalacia beneath the defective skull, suggesting that his cognitive decline could likely be attributed to repetitive cerebral contusions. Late-onset progressive cognitive decline in the context of a defective skull accompanied by extensive cystic encephalomalacia illustrates the importance of natural calvarial protection against head injury. Since the majority of patients with cleidocranial dysplasia do not wear protective helmets beyond childhood, mainly for cosmetic reasons, a discussion of whether the social disadvantage outweighs the potential risk of brain parenchymal injury may be necessary.     

Spondylo-mesomelic-acrodysplasia with joint dislocations and severe combined immunodeficiency: a newly recognised immuno-osseous dysplasia.

A newborn girl is described with an association of spondylo-acrodysplasia, mild short limbed dwarfism without significant metaphyseal changes, joint dislocations, and severe immune system dysfunction. This association is distinct from other known immuno-osseous dysplasias, including Schimke dysplasia, ADA deficiency with osseous changes, and Omenn phenotype with short limbed dwarfism.     

Geleophysic dysplasia: 7-year follow-up study of a patient with an intermediate form

Geleophysic dysplasia (MIM *231050) is a rare autosomal recessive disorder, characterized by short stature with short limbs, brachydactyly, joint contractures, and a good-natured facial appearance. Infiltration of liver and cardiac leaflets has been reported in some patients. Based on the clinical picture and the detection of lysosome-like inclusions in hepatocytes, tracheal mucosa, chondrocytes, and skin fibroblasts, the underlying cause of the conditions is considered to be a generalized lysosomal storage defect. We report on a new case born to consanguineous parents, first observed at age 8 months, and for whom a 7-year follow-up is available. Am. J. Med. Genet. 86:82–85, 1999. © 1999 Wiley-Liss, Inc.