XXY male with X-linked dominant chondrodysplasia punctata (Happle syndrome)

Happle syndrome is an X-linked dominant disorder with presumed lethality in hemizygous males; familial occurrence is rare. We describe a family with Happle syndrome affecting individuals in 3 generations. A man in this family is the first known male patient with Happle syndrome. He is severely affected; this may be due to his 47,XXY karyotype.     

Maternal systemic lupus erythematosus and chondrodysplasia punctata in two sibs: phenocopy or coincidence?

Two sibs with chondrodysplasia punctata in whom the mother was suffering from systemic lupus erythematosus are presented and the radiological features described. Comparison with other forms of chondrodysplasia punctata with a review of the relevant publications is presented and the possible association with maternal systemic lupus erythematosus is highlighted.     

Oral manifestations of severe short-limb dwarfism resembling Grebe chondrodysplasia: report of a case

The oral and dental abnormalities associated with a distinct variety of severe short-limb dwarfism are described. The patient, a 9-year-old Arab boy, had delayed development and eruption of teeth, severe oligodontia of permanent dentition, hypodontia, microdontia, supplemental incisor, enamel hypoplasia of primary teeth, doubled and abnormal frenal attachments, bifid uvula, hypoplastic maxilla, and malocclusion. Clinical and radiographic examinations revealed asymmetric dysplasia and anaplasia of long bones, craniofacial dysmorphia, prominent forehead, budlike fingers and bulbous toes, dysplastic nails, severe hearing loss, and reduced joint mobility. These features resemble, in general, those characteristic of Grebe chondrodysplasia, an extremely rare ill-defined syndrome that is inherited as an autosomal-recessive disorder.     

Neonatal lupus syndrome. Association with complete congenital atrioventricular block

Neonatal lupus erythematosus (NLE) is characterized by persistent congenital complete heart block, often without any other structural heart defects. Lupus-like dermatitis is seen transiently, more rarely hepatitis and thrombocytopenia occurs. Recent investigations have shown a close relation between NLE and maternal anti-Ro/La antibodies. These antibodies seem responsible for the destruction of the bundle of His and the AV node in the foetus. Total AV block is seen in 1:15.-22,000 of liveborn children, 70-90% of them are caused by NLE. It is difficult to identify the pregnancies at risk since at delivery most of the mothers (up to 66%) are without symptoms. If the mother has anti-Ro/La antibodies the risk for having a child with NLE is probably less than 5%. However, new investigations have shown that mothers who in addition have anti-DNA antibodies have significantly lower risk of bearing a child with NLE. In most cases foetal complete AV block is found accidentally during pregnancy. Slow foetal heart rate with the demonstration of AV dissociation should not, unless the foetus shows sign of incompensation, lead to acute delivery, but pregnancy should be monitored carefully by serial echocardiography. More than half of the children with congenital heart block need pacemaker therapy shortly after birth. The other children should be followed closely for signs of incompensation and may need pacemaker therapy later on.     

Different manifestations of the antiphospholipid antibody syndrome in a family with systemic lupus erythematosus

OBJECTIVE: Familial associations of the antiphospholipid antibody syndrome (APS) offer the opportunity to study genetic mechanisms of autoantibody production and disease, but are unusual. We identified a family, including identical twins and their mother, in which all members had systemic lupus erythematosus (SLE) and presented with different manifestations of the APS. METHODS: Review of case histories and clinical laboratory results, antiphospholipid antibody (aPL) studies, complement C4 protein and gene analysis, and HLA typing of family members were performed. RESULTS: Each of the 3 family members presented with a different clinical association of the APS. These various clinical presentations were closely temporally related. No particular aPL activity could be separated out that would account for the different manifestations, although the twin with thrombocytopenia and livedo reticularis had a strikingly high IgM anticardiolipin antibody level. C4A or C4B deficiencies could not be implicated in the autoimmune process. However, the mother and the twins shared the HLA haplotype that included the class II antigens DR4, DRw53, and DQw7, which has previously been associated with aPL production. CONCLUSION: This family study emphasizes the different clinical associations of aPL production in SLE. In addition to genetic influences that appear to include HLA class II antigens, the clinical presentations also suggest an environmental trigger.     

Chondrodysplasia punctata with multiple congenital anomalies: a new syndrome?

We report a male neonate with craniofacial dysmorphic features, multiple congenital anomalies and an unusual form of chondrodysplasia punctata. Radiographic examination revealed punctate epiphyses and coronal clefting of the thoracic spine. The hand radiographs showed some similarities to the brachytelephalangic type of chondrodysplasia punctata. However, the disorder did not fit well with any known entity of chondrodysplasia punctata or other condition characterized by punctate epiphyses.     

Cholesterol biosynthesis, peroxisomes and peroxisomal disorders: mevalonate kinase is not only deficient in Zellweger syndrome but also in rhizomelic chondrodysplasia punctata

We examined the inhibitory potency of F-1394 ((1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane -1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity and its hypolipidemic effect. F-1394 inhibited whole-cell ACAT activity in HepG2 cells with an IC50 value of 42 nM. The potency of F-1394 was greater than that of the five other ACAT inhibitors tested (YM-17E, CI-976, 57-118, CL-277,082 and DL-melinamide). In rats made hyperlipidemic by Triton WR-1339, F-1394 caused a reduction in the hepatic secretion rate of cholesterol. These data suggest that inhibition of hepatic ACAT activity helps to reduce very low density lipoprotein secretion from the liver into the circulation.     

Chronic fatigue syndrome: a novel disorder with cutaneous manifestations

Effects of heating and 60cobalt (60Co) irradiation to hepatitis C virus (HCV) RNA in sera were studied. HCV-RNA can not be detected by PCR in 10 positive serum samples after being heated at 56 degrees C for 10 hours. Whereas, HCV-RNA can still be detected in positive sera after being lyophilized and then heated at 60 degrees C for 20 hours. It suggested heating at 56 degrees C for 10 hours can inactivate HCV in sera and the sera should be in liquid status when thermal inactivation is taken. Lyophilized sera with thermal inactivation for HCV should be inactivated first and then lyophilized. But the safety of sera with heat-treatment should be further investigated. Inactivation of HCV in sera with 60Co irradiation needed extra large dose of it, and protein components in sera would obviously be altered. Therefore, inactivation of HCV in sera with 60Co irradiation is impractical.     

Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction.     

Kikuchi syndrome, Hashimoto thyroiditis and lupus serology. Apropos of a case

Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is an uncommon disease of the cervical lymph nodes occurring in young women, commonly associated with various auto-immune or infectious diseases. We describe the case of a 17 year-old girl who presented a Kikuchi's lymphadenitis occurring concomitantly with Hashimoto's thyroiditis and lupus serology as anti-nuclear, anti-DNA, anticardiolipid antibodies and hypocomplementemia. The patient was treated with prednisone and hydroxychloroquine. Thirty months after, she is doing well and hydroxychloroquine is continued.