Tel Hashomer camptodactyly syndrome: 12-year follow-up of a Hungarian patient and review.

Tel Hashomer camptodactyly syndrome (THCS) was diagnosed in a 4-month-old boy whom we have followed for 12 years. In addition to the characteristic clinical findings, he had preductal coarctation of the aorta, persistent ductus arteriosus, and multiple ventricular septal defects. The electron-microscopic evaluation of his muscle biopsy showed anomalies of the sarcoplasmic reticulum and mitochondria; the organization of the myofibrils was normal. The morphological findings suggested primary or secondary involvement of neuromuscular signal transduction and involvement of mitochondria in the development of the myopathy in this child.

Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.

Clinical manifestations of genetic instability overlap one another.

Cancer syndromes are characteristic associations of specific malignancies with various congenital anomalies. In addition to such diseases, an increased prevalence in general of chromosomal instability, malformations, immunodeficiencies, altered growth and development, and reproductive loss has been observed in both childhood leukemias and solid tumors. The overlap among these congenital disorders suggests their common prenatal, possibly genetic origin and thus the existence of a nonspecific genetic instability leading to various clinical manifestations of disturbances in cell division. Seeking for related features in family members of a patient with malignancy may be of clinical value in detecting predisposition to cancer.

[Month of birth in childhood acute lymphoblastic leukemia]. / A születés idópontja gyermekkori lymphoid leukaemiában.

INTRODUCTION: An association between date of birth influenced by certain environmental factors (such as virus infections) and malignant diseases has been suggested in some previous papers. AIMS AND METHODS: The authors analyzed the birth dates of 814 children, 0-18 years of age, in whom acute lymphoblastic leukemia was diagnosed in the period between the 1st of January 1988 and 31st of December 2000. RESULTS: No association between month of birth and manifestation of leukemia in Hungarian children could be established. CONCLUSION: The results suggest that this approach was not capable of detecting any obvious prenatal environmental factors, including virus endemics, that could have influenced the appearance of leukemia.

Ulnar/fibular ray defect and brachydactyly in a family: a possible new autosomal dominant syndrome.

The ulnar-mammary syndrome (MIM 181450) includes postaxial ray defects, abnormalities of growth, delayed sexual development, and mammary and apocrine gland hypoplasia. Brachydactyly type E (MIM 113300) presents with shortening of the metacarpals and phalanges in the ulnar ray in association with moderately short stature. We describe a three-generation family with variable expression of ulnar/fibular hypoplasia, brachydactyly, ulnar ray defects and short stature. The proband had ulnar hypoplasia with missing IV-Vth fingers, fibular hypoplasia on the right, bilateral club feet, growth retardation, a hypoplastic mid-face, an ASD and hemangiomas. She had normal mammary tissue and normal sweating. The mother had short stature, midfacial hypoplasia, a hypoplastic ulna and hypoplasia of the IVth metacarpal (brachydactyly) on the right without other associated malformations. The maternal grandfather had mild bilateral fibular hypoplasia and midphalangeal brachydactyly of the IV-Vth toes. His sister had mild short stature and shortening of the IVth metacarpal of the left hand. Two-point linkage analysis with microsatellite markers spanning the Ulnar-Mammary locus at 12q24.1 did not confirm linkage. The patients may have a previously undescribed syndrome.

Association of wilms tumor with spinal dysraphism.

Previous data suggested an association of vertebral anomalies with Wilms tumor. At the same time, vertebral midline fusion defects are often indicated by dermal anomalies over the spine. In the present study the prevalence of both occult spina bifida and cutaneous signs of spinal dysraphism was significantly higher in 50 Wilms patients than in 180 control children (18.0 versus 4.4%, p <.01, and 35.9 versus 17.5%, p <.02, respectively). Family investigations are needed to answer the question whether signs of spinal dysraphism in parents and sibs of patients may be regarded as indicators of an increased risk of Wilms tumor in the family.

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia.

UNLABELLED: Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G > C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone. CONCLUSION: we suggest that the observed metabolic alterations are secondary to the RUNX2 gene mutation affecting early bone maturation and turnover. This is the first description of biochemical findings of hypophosphatasia in patients with cleidocranial dysplasia.