Fragile X syndrome and myelodysplasia discovered during pregnancy.

We describe a female patient who presented at pregnancy with leucopenia and was found to suffer from both fragile X syndrome [Fra(X)] and myelodysplastic syndrome with cytogenetic abnormalities in bone marrow cells including 4q+ and deletion D13. To date only four cases of Fra(X) syndrome with malignant tumours (one haematological), all in male patients, have been reported. We believe that the occurrence of the myelodysplastic syndrome in this patient could be more than coincidental.

[Huntington's disease: ethical aspects of presymptomatic testing].

Huntington's disease is an autosomal dominant entity with onset mostly in middle age. Neurological signs and psychosis evolve without possibility of treatment or alleviation. Genetic counseling of relatives of patients has changed since the development of presymptomatic testing. Ethical issues and dilemmas associated with the application of this technological advance are reviewed as a result of a request by a mother to perform presymptomatic testing in her young daughter whose father has Huntington's disease.

The dilemma of chromosomal mosaicism in chorionic villus sampling--'direct' versus long-term cultures.

Chromosomal mosaicism is one of several unanswered dilemmas in first-trimester prenatal diagnosis. We report the course of a pregnancy in which a normal karyotype was detected on direct CVS preparation and fetal blood, 100 per cent trisomy 21 in one long-term CVS culture, and low-rate trisomy 21 mosaicism in a second long-term CVS culture and amniocentesis. The phenotypically normal infant had a 6 per cent mosaicism of trisomy 21. It appears that a persistent low-rate mosaicism in different tissues may be indicative of the true status of the fetus.

Homozygosity for autosomal dominant Marfan syndrome.

Marfan syndrome is an autosomal dominant condition with varying phenotypic manifestations. Affected persons are usually heterozygotes. A family is presented in which the gene for this syndrome is segregating in a large number of members. Two sibs suffered from unusually severe, identical, and fatal manifestations from birth, their parents having mild cardiovascular and somatic symptoms common in Marfan syndrome. Investigation of collagen biosynthesis in fibroblasts revealed no abnormalities in fibronectin and procollagen I and III synthesis and secretion or in the procollagen to collagen conversion. We suggest that these two sibs are examples of homozygosity for the Marfan syndrome gene, based on the large number of affected members, the absence of additional consanguinity, manifestation of the syndrome in both parents, and the severity of the disease in the two sibs.

Genetic counselling for trisomy 20 mosaicism in amniotic fluid cell cultures.

Trisomy 20 mosaicism in amniotic fluid cell cultures has an obscure origin and significance. In only a few cases has the mosaicism been confirmed in fetal tissues, but never in neonatal tissues. There is some indication that the trisomic cells might originate from epithelial cells deriving from the urinary tract. A review of 20 demonstrated cases reveals that no consistent malformation pattern is associated with this finding. Since it is questionable whether the presence of this mosaicism in amniocentesis can be regarded as a manifestation of abnormal fetal development, we suggest that it does not justify interruption of pregnancy. Postnatal cytogenetic studies and follow-up are indicated in these infants.

Bisatellited microchromosomes and multiple congenital malformations.

The significance of small additional metacentric chromosomes is still unclear. A patient is reported with multiple congenital malformations involving craniofacial structures, the cardiovascular system and gastrointestinal tract, in whom an extra small bisatellited chromosome was detected. The maternal karyotype revealed a marker number 9 chromosome. These cases present a true diagnostic dilemma in genetic counseling, since chromosomal instability may occur in the presence of parental minor structural chromosomal changes.

Absent ulna in the Klippel-Feil syndrome: an unusual associated malformation.

A patient is reported with a severe type 2 Klippel-Feil syndrome, and absent ulna and ulnar ray. The severity of the musculo-skeletal involvement did not allow for corrective procedures. This uncommon association of skeletal malformations has not been previously reported. Since this syndrome has been described in families as a possible autosomal recessive trait, a 25% recurrence risk and the possibility of prenatal detection by fetal visualization methods should be taken into consideration.

Prenatal diagnosis of severe congenital malformations associated with elevated amniotic fluid alpha-feto protein.

Two cases of severely malformed infants with abnormal fetal images on B-scan sonography and markedly elevated amniotic fluid AFP are presented. There was no evidence of neural tube anomalies. The importance of an amniocentesis and AFP in pregnancies with an abnormal fetal image on B-scan sonography is emphasized, taking into consideration that most pregnancies with elevated fluid AFP have serious fetal anomalies.