Split-cord malformation in a girl with Angelman syndrome: a mere coincidence?

We present a case of a girl with both Angelman syndrome and split-cord malformation. The child was initially referred at the age of 2.5 years, for developmental delay and a possible diagnosis of spina bifida occulta, based on the presence of a hair tuft located on the midline of the lumbar area. Magnetic resonance imaging of the spine showed split-cord malformation below L1, whereas a cytogenetically detected deletion of chromosome bands 15q11-q13 (SNRPN) confirmed the clinical diagnosis of Angelman syndrome. Split-cord malformation or diastematomyelia is a rare form of spina bifida occulta that occurs sporadically and is not particularly related to specific syndromes. Hair patches or other distinctive cutaneous stigmata such as those seen in the present case have not, to our knowledge, been reported in other patients with Angelman syndrome; therefore, the association of Angelman syndrome and split-cord malformation in this child is probably coincidental. Spinal cord abnormalities have not been consistently reported in patients with Angelman syndrome; only one adult patient with Angelman syndrome and spina bifida occulta has been reported, and this association was probably considered fortuitous. However, some relatively uncommon clinical features such as deterioration of gait, lower limb malformations, and bladder dysfunction, particularly as the patients age, although nonspecific, are reminiscent of such a cause. We therefore urge clinicians to look for cutaneous stigmata along the spine and consider the evaluation of the spinal cord in children with apparent paraparesis, out of proportion to that usually seen in Angelman syndrome, should our case report not just be a coincidental observation.     

X-Linked agammaglobulinemia in a child with Klinefelter’s syndrome

Bruton’s agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter’s syndrome caused by an additional X chromosome is the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.     

Colobomatous microphthalmia,microcephaly with cerebellar hypoplasia: Association or new syndrome?

We report on a 3.5‐year‐old girl with microcephaly, microphthalmia, coloboma of the iris, mild developmental delay, and other minor anomalies. Neuroimaging showed marked cerebellar and vermian hypoplasia. This condition has not been described previously and is discussed in the context of the “micro syndrome,” together with other similar syndromes. Our case highlights the heterogeneity of the “microphthalmia plus brain malformations” group of patients. Am. J. Med. Genet. 92:278–280, 2000. © 2000 Wiley‐Liss, Inc.     

Apoptosis or necrosis for tumor immunotherapy: what's in a name?

Here we discuss how the mechanisms by which tumor cells are killed in vivo by gene transfer affects their immunogenicity. Our own work has shown that necrotic cell death induces immunological activation signals which recruit, load, activate and mature appropriate subsets of antigen-presenting cells. In contrast, for apoptotic cell death to be immunogenic, signals additional to cell death alone must be provided within the milieu of the dying tumor. Our conclusion is that the immunogenicity of tumor killing is determined by a combination of factors, including the mechanism of killing, the levels of cell death, the local environment that exists within the dying tumor and, as a result, the nature of the immune/scavenger cells which are present at the time of antigen release. Knowledge of how these factors can influence the immune system and lead to the breaking of tolerance to tumor-associated antigens, can potentially be exploited in the design of effective immunotherapies for cancer using gene transfer.     

Guillain-Barré syndrome in child with prolong intubation

Guillain-Barré syndrome (GBS) is an acute demyelinating disorder of the peripheral nervous system that results from an aberrant immune response directed at peripheral nerves. A typical GBS patient presents with rapidly ascending symmetrical weakness, which may progress to respiratory failure in 30% of patients. There are no definite criteria exists in GBS in children regarding prolonged ventilation. Here we report a child of GBS requiring prolonged intubation and ventilation for 60 days who afterward had a complete recovery. We present this case to highlight the importance that even in children prolonged intubation and ventilation of GBS case prognosis can be good.     

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node. Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.     

Is it a new syndrome or a clinical variability in cerebro-oculo-nasal syndrome?

We present a male infant 2.5-months old with asymmetric skull, anophthalmia, apparent hypertelorism, abnormal nares, unilateral cleft lip and palate, and structural abnormalities of the central nervous system. These findings are similar to cerebro-oculo-nasal syndrome except for the appearance of nose. This case is either a clinical variability in cerebro-oculo-nasal syndrome or a new entity.     

Prevalence of Acanthamoeba and superbugs in a clinical setting: coincidence or hyperparasitism?

Antibacterial strategies to eradicate superbugs from hospitals/nursing homes have had limited success, suggesting the need for employing innovative preventative measures and better understanding of the prevalence of microbial pathogens in close proximity of susceptible populations. A total of 120 environmental samples were collected from the Aga Khan University hospital. Amoebae were identified using morphological characteristics as well as PCR using genus-specific primers, while bacteria were identified using standard biochemical testing. Out of 120 samples tested, 52 (43.3 %) samples were positive for Acanthamoeba, while all 120 (100 %) samples were positive for bacteria. Following bacterial identification, samples showed mixed bacterial populations. Out of 120 samples, 76 (63.3 %) samples were positive for Bacillus spp., 64 (53.3 %) samples were positive for Corynebacterium spp., 32 (26.6 %) samples were positive for Staphylococcus spp., and 9 (7.5 %) samples were positive for Micrococcus spp. The antibiotic susceptibility showed that all bacterial isolates recovered were multiple drug-resistant. The current findings suggest that Acanthamoeba and bacteria coexist in a clinical environment. Given that Acanthamoeba can harbor bacteria, anti-amoebic approaches may represent a strategy in eradicating “superbugs” from the clinical setting in addition to the current measures.     

Congenital pulmonary lymphangiectasia and other anomalies in a child: Provisionally unique syndrome?

Congenital pulmonary lymphangiectasis is a rare anomaly that is causally heterogeneous. It can occur as either an isolated finding or one manifestation of several multiple congenital anomaly syndromes. We describe a child with congenital pulmonary lymphangiectasis and other anomalies who likely has a provisionally unique condition. © 1996 Wiley-Liss, Inc.     

CYP46: a risk factor for Alzheimer's disease or a coincidence?

Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46). Although serum and cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol are altered during the progress of Alzheimer's disease, studies carried out to date in different populations on the association of CYP46 gene polymorphisms and risk of AD have been inconclusive. In this report, we analyzed CYP46 polymorphisms in 215 Polish AD cases and 173 healthy individuals. A fragment of CYP46 intron 2 was amplified by PCR reaction and sequenced. We discovered a new single nucleotide substitution in CYP46 intron 2, but found no difference in particular genotype or allele frequencies between AD patients and controls. However, the GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE varepsilon4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable.     

Is autosomal recessive deafness associated with oculocutaneous albinism a “coincidence syndrome”?

Hearing impairment is frequently found associated with pigmentary disorders in many syndromes. However, total oculocutaneous albinism (OCA) associated with deafness has been described only once, by Ziprkowski and Adam (Arch Dermatol 89:151–155, 1964) in an inbred family. A syndrome associating deafness and OCA was suggested by the authors, but two separate recessive genes segregating in this inbred group were also proposed later by Fraser (OMIM # 220900). Combined deafness and total OCA were also observed by us in a family originally reported to be nonconsanguineous but in which haplotyping showed evidence of a common ancestry: the proband was affected by both diseases, one of his sisters had only OCA and another sister had only deafness. Both the proband and his deaf sister were found to be homozygotes for the 35delG mutation (GJB2 gene), the most frequent cause of hereditary deafness. Linkage analysis with markers close to the four known OCA loci excluded linkage to OCA1, OCA2, and OCA3, and homozygosity in markers near OCA4 locus was observed. Sequencing of the corresponding gene (MATP) revealed a c.1121delT mutation, which leads to a stop codon at position 397 (L374fsX397). Clearly, the combined occurrence of deafness and albinism in this pedigree was due to mutations in two different genes, showing autosomal recessive inheritance. We speculate that the putative syndrome reported by Ziprkowski and Adam might have resulted from the co-occurrence of autosomal recessive deafness and albinism in the same pedigree, as suggested by Fraser.     

Noonan-like syndrome with loose anagen hair: a new syndrome?

We present three children with short stature, the same facial phenotype, macrocephaly, enlarged cerebral spinal fluid spaces, short neck with redundant skin, severe GH deficiency, mild psychomotor delay with attention deficit/hyperactivity disorder (ADHD), mild dilatation of the pulmonary root in two of them, and a unique combination of ectodermal abnormalities. Their appearance, not completely typical of Noonan syndrome, the behavioral phenotype, GH deficiency, darkly pigmented and hairless skin, and the unusual aspect of the hair, defined as loose anagen hair syndrome did not fit any known condition. We postulate that these children may represent a distinct, previously unreported syndrome that we would name "Noonan-like syndrome with loose anagen hair".     

D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon?

Succinic semialdehyde dehydrogenase (SSADH) deficiency and D-2-hydroxyglutaric aciduria (D-2-HGA) are rare inborn errors of metabolism primarily revealed by urinary organic acid screening. Three patients with proven SSADH deficiency excreted, in addition to GHB considerable amounts of D-2-HG. We examined whether these patients suffered from two inborn errors of metabolism by measuring D-2-HG concentrations in the culture medium of cells from these patients. In addition, mutation analysis of the D-2-hydroxyglutarate dehydrogenase gene was performed. Normal concentrations of D-2-HG were measured in the culture media of fibroblasts or lymphoblasts derived from the three patients. In one patient, we found a heterozygous likely pathogenic mutation in the D-2-hydroxyglutarate dehydrogenase gene. These combined results argue against the hypothesis that the patients are affected with "primary" D-2-HGA in combination with their SSADH deficiency. Moderately increased levels of D-2-HG were also found in urine, plasma, and cerebrospinal fluid samples derived from 12 other patients with SSADH deficiency, revealing that D-2-HG is a common metabolite in this disease. The increase of D-2-HG in SSADH deficiency can be explained by the action of hydroxyacid-oxoacid transhydrogenase, a reversible enzyme that oxidases GHB in the presence of 2-ketoglutarate yielding SSA and D-2-HG.