Humero-radial synostosis, microcephaly, short corpus callosum, and abnormal genitalia in sibs.

We report on two male sib fetuses with humero-radial synostosis and thumb hypoplasia, microcephaly with simplified gyral pattern, short corpus callosum and ambiguous genitalia. The main clinical, anatomopathological and imaging findings are presented and compared with previous cases of humero-radial synostosis as a prominent manifestation and with the X-linked lissencephaly with ambiguous genitalia syndrome (X-LAG). To our knowledge, this combination of anomalies has never been described before, and we propose that this disorder comprises a new humero-radial synostosis syndrome with an autosomal recessive or X-linked pattern of inheritance.

A new syndrome of congenital generalized osteosclerosis and bilateral polymicrogyria.

We report a 29-week male fetus with healthy consanguineous parents. He showed a severe sclerosing bone disorder affecting all skeletal elements, resulting in insufficient modeling, generalized densification, and fragility of the skeleton. This skeletal dysplasia was associated with an abnormal craniofacial development (hypertelorism, severe microretrognathia, cleft palate, absent epiglottis, reduced number, and mineralization of teeth buds) and abnormal terminal phalanges. Neuropathologic examination showed bilateral fronto-parietal cerebral polymicrogyria. This syndrome appears to represent a new variant of congenital sclerotic bone disorder of unknown origin. Autosomal recessive inheritance is possible.

Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

Trisomy of the short arm of chromosome 4 is a well-known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi-lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations. The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1). The etiology of HPE is very heterogeneous; it includes non-genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4.