Jan-Hein Cobben

Oculocerebrocutaneous syndrome: report of three additional cases and aetiological considerations

The oculocerebrocutaneous (OCC) syndrome is characterized by the presence of orbital cysts and microphthalmia/anophthalmia, focal hypo‐and aplastic skin defects, skin appendages and cerebral malformations. Most of the patients suffer from psychomotor retardation and seizures. To date, 23 patients in total have been reported. We report on three additional cases which illustrate the broad clinical spectrum of this disorder. In one case, the differentiation between OCC syndrome and encephalocraniocutaneous lipomatosis was difficult. A brief review of the clinical features of OCC syndrome is given. Possible aetiological hypotheses are discussed, namely survival of a lethal mutation by mosaicism, an autosomal dominant mutation and external causal factors. Disruption of the anterior neuroectodermal plate seems to be the most probable pathogenic mechanism.

Variable expression of the popliteal pterygium syndrome in two 3-generation families

Three successive generations in two families affected with the popliteal pterygium syndrome are reported. While expression of the syndrome was relatively mild in the first and second generation, the patients in the third generation showed the full‐blown syndrome. Differential diagnosis between mildly affected patients with the popliteal pterygium syndrome and those with Van der Woude syndrome is difficult and may even be impossible. The present observations further support the hypothesis that both syndromes may in fact represent variants of the same condition.

On the many faces of Leber hereditary optic neuropathy

Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between the eyes becoming affected, course of the disease, concomitant disorders, additional test results, final visual acuity, and/or results of mtDNA analysis. Moreover, the pedigrees themselves did not suggest maternal inheritance. We analysed the diagnostic and clinical genetic difficulties related to the atypical aspects of these pedigrees. We conclude that mtDNA analysis is justified in every case of optic nerve atrophy with no clear cause. Identification of one of the three LHON specifically associated mtDNA mutations is essential to confirm the diagnosis.

A SUBLOCUS OF THE MULTICOPY MICROSATELLITE MARKER CMS1 MAPS PROXIMAL TO SPINAL MUSCULAR-ATROPHY (SMA) AS SHOWN BY RECOMBINANT ANALYSIS

The critical region containing the spinal muscular atrophy (SMA) gene is flanked by the 5q11–q13 markers, D5S435 and D5S557, as determined by linkage analysis. Here we present the results of an analysis of a Dutch SMA family with the multicopy microsatellite marker CMS1. A crossover is revealed in the critical SMA region. We conclude that at least one of the CMS1 subloci maps proximal to the SMA gene. This reduces the minimal SMA region from approximately 1.4 Mb to 600–700 kb.