N. Van Regemorter

Two unrelated children with partial trisomy 1q and monosomy 6p, presenting with the phenotype of the Larsen syndrome

SummaryTwo unrelated children presented with similar clinical features (facial dysmorphism and multiple joint dislocations) suggesting the diagnosis of Larsen syndrome. Both carried an inherited unbalanced translocation resulting in partial trisomy 1q and partial monosomy 6p. Analysis of skin collagen from one of the probands disclosed a decreased α1/α2 chain ratio of collagen type I, increased thermal stability and increased hydroxylation of proline and lysine. The present findings suggest that, as a result of the chromosome rearrangements, both patients have a mutation on a gene involved in collagen production, located either on chromosome 1q or, more probably, on 6p. It is furthermore suggested that other cases of Larsen syndrome are the result of a similar mutation.

A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late-infantile metachromatic leukodystrophy

SummaryMetachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two unrelated Belgian patients with late-infantile MLD. The mutation predicts an aspartic acid-to-histidine substitution at position 255 in arylsulphatase A (D255H), in a highly conserved region among sulphatases. Transient expression of the mutation in COS cells did not show an increase in ARSA activity. Both patients were compound heterozygotes carrying the frequent splice site mutation in intron 2 (459+1G→A) on the other allele.

Alphafetoprotein (AFP), concanavalin A non-reactive AFP and specific acetylcholinesterase in amniotic fluid from pathological pregnancies. Predictive values for open spina bifida.

Alphafetoprotein (AFP) and concanavalin A non-reactive alphafetoprotein determination and the acetylcholinesterase (AchE) qualitative test have been performed on amniotic fluid samples from 33 normal pregnancies, 44 pregnancies with fetal malformations and 8 normal pregnancies with elevated amniotic fluid alphafetoprotein (3 false positive AFP results, 5 contaminations with fetal blood). The validities of these three tests in detecting abnormal pregnancies are compared. The usefulness of the existing complementary tests in the detection of neural tube defects in a low neural tube defect incidence area is discussed. Risk figures for open spina bifida according to the prior risk situation and the results of maternal serum AFP, amniotic fluid AFP, AchE qualitative test and ultrasound examination have been calculated.

Charcot-Marie-Tooth disease associated with retinal pigment dystrophy and protanopia

SummaryNeurological, ophthalmological and genetic investigations were performed on a family, a member of which presented with a rare association of tapeto-retinal degeneration, protanopia and Charcot-Marie-Tooth disease (CMT), and asked for genetic counselling. The neurological enquiry was completed by measurement of motor nerve conduction velocity in several members of the family. The propositus was submitted to a muscle biopsy. The ophthalmological examination included ophthalmoscopy, fluorescein angiography, electroretinogram and electrooculogram. The propositus, a woman aged 40, had typical CMT disease and her father also had a mild form of it. She had protanopia as had her father, her son and her nephew. In addition she had large macular pigmented changes, described as retinal dystrophy, “flavus flavimaculatus.” Her mother had only senile pigmented modification of the fundus and her three daughters had mild macular pigmented changes, like “salt and pepper.” Two genes are probably involved: one for protanopia with X linked recessive inheritance, the other responsible of CMT and tapetoretinal degeneration, with an autosomal dominant inheritance, giving a 50% risk of recurrence.ZusammenfassungEin Patient wies die seltene Kombination einer tapetoretinalen Degeneration, einer Protanopie und einer Charcot-Marie-Tooth-Krankheit auf. Die Familie dieses Kranken wurde dann eingehend neurologisch, ophthalmologisch und genetisch analysiert. Es wurde auch eine Bestimmung der motorischen Erregungsleitungsgeschwindigkeit bei mehreren Familienmitgliedern durchgeführt. Beim Patienten wurde auch eine Muskelbiopsie ausgeführt. Die ophthalmologische Untersuchung umfaßte Ophthalmoskopie, Fluoreszenzangiographie, Elektroretinographie und Elektrookulographie. Die 40jährige Proposita wies eine typische Charcot-Marie-Tooth-Krankheit auf, und ihr Vater hatte die Erkrankung in einer milden Form. Sowohl die Proposita wie ihr Vater wiesen eine Protanopie auf, ebenso Sohn und Neffe der Patientin. Sie hatte außerdem ausgedehnte Pigmentverschiebungen im Makulabereich, die als retinale Dystrophie im Sinne eines Fundus Flavus flavimaculatus“ beschrieben wurden. Ihre Mutter hatte lediglich senile Pigmentveränderungen des Augenfundus, und ihre drei Töchter hatten diskrete makulare Pigmentveränderungen im Sinne eines „Pfeffer-und-Salz“-ähnlichen Fundus. Wahrscheinlich sind zwei Gene für die Veränderungen verantwortlich: das eine für die Protanopie mit X-chromosomal gebundener rezessiver Vererbung, das andere für die Charcot-Marie-Tooth-Erkrankung verantwortlich sowie für die tapetoretinale Degeneration, mit einer autosomal dominanten Vererbungsweise, welche mit einem 50%igen Risiko der Übertragung verbunden ist.

Alpha-thalassémie majeure : à propos d’un cas de dépistage anténatal et revue de la littérature

Homozygous alpha-thalassaemia or Barts hydrops fetalis is a genetic disease with autosomal recessive transmission. The condition is lethal for the fetus because of hypoxia and anemia. For the mother there is an increased risk of the severe forms of preeclampsia and its complications. The diagnosis can be suspected in presence of suggestive ultrasonographic anomalies, where both parents come from South-East Asia or China. Confirmation is based on the identification of the typical deletions or mutation of the alpha globin gene by molecular genetics. We report a rare clinical case of Barts hydrops fetalis diagnosed because of fetal growth retardation, fetal cardiomegaly and increased size of placenta on the 26 weeks fetal echography. This case underscores the need to include the alpha thalassemias in medical and midwifery education in countries where they were almost inexistent a generation ago.

Cas cliniqueAlpha-thalassémie majeure : à propos d’un cas de dépistage anténatal et revue de la littératureMajor alpha-thalassemia: Antenatal diagnosis, case report and literature review

Homozygous alpha-thalassaemia or Barts hydrops fetalis is a genetic disease with autosomal recessive transmission. The condition is lethal for the fetus because of hypoxia and anemia. For the mother there is an increased risk of the severe forms of preeclampsia and its complications. The diagnosis can be suspected in presence of suggestive ultrasonographic anomalies, where both parents come from South-East Asia or China. Confirmation is based on the identification of the typical deletions or mutation of the alpha globin gene by molecular genetics. We report a rare clinical case of Barts hydrops fetalis diagnosed because of fetal growth retardation, fetal cardiomegaly and increased size of placenta on the 26 weeks fetal echography. This case underscores the need to include the alpha thalassemias in medical and midwifery education in countries where they were almost inexistent a generation ago.