V. Consiglio

14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with intellectual disability and bilateral microphthalmia, but without holoprosencephaly.

Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at least 10 cases involving this region have been described and all patients showed a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated with intellectual disability (ID), bilateral microphthalmia, and coloboma, without cerebral anomalies typical of HPE. Except for ocular defects (i.e., microphthalmia, coloboma) consistent with HPE‐type anomalies, the minor facial dysmorphia was not suggestive for HPE and the absence of cerebral anomalies should rule out this diagnosis. The deletion of the potential HPE candidate genes NPAS3, EAPP, SNX6, and TULIP1, raises doubts about their pathologic role in determining HPE. It is likely that deletions of HPE genes are not sufficient to cause HPE, and that multiple genetic, chromosomal, and environmental factors interact to determine the variable clinical expression of HPE. This is the first case of a 14q deletion encompassing the HPE8 locus with the only features consistent with HPE‐type anomalies affecting the ocular system (i.e., microphthalmia, coloboma), and without cerebral anomalies specific for HPE. The inclusion of potential HPE candidate genes in the deletion raises the question whether this patient is affected by a less severe form of HPE (HPE microform), or whether he has a new ID/MCA deletion syndrome.

Deletion of NSD1 exon 14 in Sotos syndrome: first description

Sotos syndrome (OMIM 11755) is a congenital disorder characterized by overgrowth, advanced bone age, macrocephaly, facial dysmorphic features and variable degrees of mental retardation. Most cases are sporadic (Cole and Hughes 1990), but familial cases with autosomal dominant inheritance have also been described (Tei et al. 2006). The major diagnostic criteria established by Cole and Hughes were in force for clinical diagnosis of Sotos syndrome until 2002, when Kurotaki et al. (2002) discovered that haploinsufficiency of the nuclear receptor set domain containing protein 1 gene (NSD1) causes Sotos syndrome. Tatton-Brown et al. (2005) reviewed 239 patients with NSD1 abnormalities: overgrowth, facial dysmorphisms and learning disability were present in 90% of these patients; the height and head circumference of 10% of the subjects were within normal range. Advanced bone age was found in 76% of individuals. The authors concluded that overgrowth is not obligatory for the diagnosis of Sotos syndrome and advanced bone age should not be considered as mandatory diagnostic criterion, in agreement with other authors (Leventopoulos et al. 2009a). However, classic phenotype of Sotos syndrome is conventionally considered as one of the most frequent overgrowth conditions, although its variable expressivity has been clearly noted. Craniofacial abnormalities include macrocephaly, broad forehead, high hairline, downslanting palpebral fissures, prominence of the pointed chin, mild micrognatia. Cardiac and renal anomalies, seizures and scoliosis are described in 15%–30% of cases with variable degrees of severity (Tatton-Brown and Rahman 2007; Leventopoulos et al. 2009b). A broad spectrum of other clin-

Non-mosaic Tetrasomy Yp by Complex Isodicentric Rearrangement of the Y Chromosome: Prenatal Diagnosis with Cordocentesis in a Fetus with Abnormal Obstetric Ultrasound

Tetrasomy Y is a very rare event, especially when it is present in a complete form. It is determined by complex rearrangement of the Y chromosome. Clinical features include psychomotor delay, skeletal abnormalities and facial dysmorphism. We report on a case of prenatal diagnosis of non-mosaic tetrasomy Yp, performed by karyotype and fluorescence in situ hybridization (FISH) on fetal blood. These analyses showed the presence of two isodicentric Y, with two copies of SRY and one copy of DXZ1 (XCEN) in each one. Karyotype was characterized as 47; X, Isodicentric (Y) (pter→q12::q12→pter) x2 (SRYx4). Cytogenetic studies were performed after detection of abnormal prenatal ultrasound, showing severe intrauterine growth restriction (symmetric IUGR), hydropic placenta, mild cerebellar hypoplasia, microretrognathia, hyperechogenic bowel with slight distension, dilation of recto-sigmoid tract, ambiguous genitalia, clinodactyly of the right fifth finger, suspected polydactyly. It was not possible to make a clear genotypephenotype correlation because a pregnancy interruption was performed.