New mutation in the CYLD gene within a family with Brooke‐Spiegler syndrome

Brooke‐Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12‐q13. We describe a family, in which we performed a molecular‐genetic examination and found a new mutation in exon 19 in the CYLD gene leading to a frameshift. It is important to be aware of this syndrome and its pathogenesis as its phenotypic features can vary so that apparently different diseases are caused by the same genetic defect. In addition, there may be malignant transformation of the generally benign tumors, so that a timely diagnosis is essential for appropriate monitoring and therapy.     

Maternal isochromosome 7q and paternal isochromosome 7p in a boy with growth retardation

A 12-year 9-month-old boy with postnatal growth retardation, normal psychomotor development, and minor anomalies that included a triangular-shaped face, small nose, and narrow and high-arched palate is reported. The constitutional karyotype was 46,XY,i(7)(p10),i(7)(q10). Molecular investigations revealed the presence of a maternal isodisomy 7q and a paternal isodisomy 7p. The clinical and molecular findings are notably congruent with a recently reported case and support the hypothesis of one or more maternally imprinted genes located on the long arm of chromosomes 7 that regulate, in particular, postnatal growth.     

Upper limb deficiencies and associated malformations: A population-based study

As part of an ongoing analysis of limb deficiencies occurring among 1,213,913 consecutive livebirths in British Columbia during the years 1952–1984, all cases with deficiencies of the upper limbs were analysed with a view to identifying associated patterns of anomalies. This analysis resulted in seven subgroups. For each subgroup, incidence figures for cases with and without additional anomalies were calculated separately. The proportion of cases with additional anomalies varied markedly by subgroup. For example, 89% of cases with longitudinal defects of the radius had additional malformations, while only 28% of cases with transverse defects of the radius had other organ anomalies (χ² = 40.55; P < 0.001, one degree of freedom). A preponderance of males was found among the cases with associated defects, particularly in the group with longitudinal defects of the radius (28 males, 14 females; χ² = 14.10; P < 0.001). Clustering of specific patterns of associated malformations is described within subgroups. © 1992 Wiley-Liss, Inc.     

Microcephaly-lymphedema syndrome: Report of a family with short stature as additional manifestation

Patients with the rare autosomal dominant microcephaly-lymphedema syndrome have apparently normal intelligence. We report on a boy with microcephaly, lymphedema, and short stature as an additional manifestation. The family history of our patient suggests autosomal dominant inheritance with reduced penetrance and variable expressivity. However, X-linked inheritance cannot be excluded. Am. J. Med. Genet. 80:506–509, 1998. © 1998 Wiley-Liss, Inc.     

Lethal multiple pterygium syndrome: Suggestion for a consistent pathological workup and review of reported cases

We report on 2 brothers with lethal multiple pterygium syndrome (LMPS) born to non-consanguineous parents as late spontaneous abortions. Both fetuses presented with massive nuchal edema, and facial anomalies including cleft palate and broad ribs. Apparently, several subgroups of LMPS exist. Differentiation is difficult, as there is no consistent agreement on a workup protocol for autopsies. We compared the findings in the literature on cases with LMPS, and we suggest a standardized workup as an initial step for more efficient differentiation between various subgroups. Am. J. Med. Genet. 68:82–85, 1997 © 1997 Wiley-Liss, Inc.     

Neurofibromatosis type 1 and associated clinical abnormalities in 27 children

Neurofibromatosis type 1 is the most common of the phakomatoses and the clinical follow-up is an interdisciplinary challenge. The data of 27 patients with NF1 were systematically reviewed and compared to data from the literature. All of our patients had clinical signs of NF1. Besides the classic criteria café-au-lait spots (100%), freckling (48,1%), positive family history (44,1%), neurofibromas (40,7%), Lisch nodules (22,2%) and optic pathway tumors (22,2%) there were developmental delay (40,7%), macrocephaly (33,3%), strabism (29,6%), scoliosis (18,5%), epilepsy (14,8%), pubertal anomalies (14,8%), short stature (11,1%) and tics. Morphologically, CNS hamartomas (55,5%), astrocytomas (22,2%) and one pheochromocytoma became apparent. Special findings consist of one aneurysm of internal carotic arteria, juvenile xanthogranulomas, a case of pulmonary stenosis and an intracardial tumor. Four new mutations in the NF1 gene were found. Regular screening of optic glioma with MRI had no clinical significance. In contrast to other authors, one of our patients with optic glioma showed clinical progress after twelve years of age. The detection of astrocytomas led only to therapeutic consequences, when clinical signs or symptoms occurred. As with other authors, we found no potential for CNS hamartoma to proliferate. In three cases with pubertal anomalies we found CNS gliomas, which indicates the need for MRI. The expense of screening, apart from clinical surveillance, seems inadequate in relation to clinical relevance and costs. We describe four new mutations in the NF1 gene; there have been no specific genotype-phenotype correlations. Neurofibromatosis type 1 and associated clinical abnormalities in 27 children.