Hollander, N. den

Further delineation of Pitt-Hopkins syndrome: Phenotypic and genotypic description of 16 novel patients (Article)

2008-11-01T00:00:00Z

Background: Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation. Methods: TCF4 mutational analysis was performed in 117 patients with PTHS-like features. Results: In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies. Conclusion: This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.

Congenital disorder of glycosylation type Ia presenting with hydrops fetalis (Article)

2007-04-01T00:00:00Z

There is a growing awareness that inborn errors of metabolism can be a cause of non-immune hydrops fetalis. The association between congenital disorders of glycosylation (CDG) and hydrops fetalis has been based on one case report concerning two sibs with hydrops fetalis and CDG-Ik. Since then two patients with hydrops-like features and CDG-Ia have been reported. Two more unrelated patients with CDG-Ia who presented with hydrops fetalis are reported here, providing definite evidence that non-immune hydrops fetalis can be caused by CDG-Ia. The presence of congenital thrombocytopenia and high ferritin levels in both patients was remarkable. These might be common features in this severe form of CDG. Both patients had one severe mutation in the phosphomannomutase 2 gene, probably fully inactivating the enzyme, and one milder mutation with residual activity, as had the patients reported in literature. The presence of one severe mutation might be required for the development of hydrops fetalis. CDG-Ia should be considered in the differential diagnosis of hydrops fetalis and analysis of PMM activity in chorionic villi or amniocytes should also be considered.

Sonographic assessment of normal and abnormal fetal development; early and late aspects (Doctoral Thesis)

2002-01-09T00:00:00Z

This thesis consists of two parts. The first part deals with an increasingly important area of first and early second trimester (<14 weeks) normal and abnmmal fetal sonoanatomy and its validity and impact in the early diagnosis of fetal anomalies in a high-risk population. The second part of the thesis focuses on the clinical genetic aspects of fetal anomaly scanning with emphasis on the second half of gestation. Single fetal anomalies diagnosed by ultrasound may be associated with other and often minor anomalies. which pre- or postnatally may be identified as exogenic or genetic syndromes with specific recurrence risks. This will have important implications for genetic counseling

Two cases of Robertsonian translocations in oligozoospermic males and their consequences for pregnancies induced by intracytoplasmic sperm injection (Article)

1997-01-01T00:00:00Z

Two case histories are presented documenting structural chromosome abnormalities in infertile males. The abnormalities were detected only after application of intracytoplasmic sperm injection (ICSI) was repeatedly unsuccessful or resulted in an abnormal pregnancy. A mosaic Robertsonian translocation 45,XY,der(13;13)(q10; q10)/46,XY,t(13;13)(p10;p10), der(13p;13p) incompatible with normal offspring was found in a male with extreme oligozoospermia after three subsequent ICSI treatments were unsuccessful and one had resulted in a spontaneous abortion. A second case involved a Robertsonian translocation 45,XY,der(13;14)(q10;q10) which was detected in a male with extreme oligozoospermia after ultrasound abnormalities were found in an ICSI-induced twin pregnancy. Amniocentesis showed an unbalanced 46,XY,+13,der(13;14)(q10;q10) karyotype in one twin and a Robertsonian 45,XX,der(13;14)(q10;q10) karyotype in the other twin. Chromosome analysis of males with abnormal sperm characteristics is advised prior to ICSI.