Monosomy1p36.3 and trisomy 19p13.3 in a child with periventricular nodular heterotopia.

Monosomy 1p36 is a clinically recognizable syndrome that is considered to be the most common terminal deletion syndrome. It has characteristic clinical features that include craniofacial dysmorphism, congenital anomalies, hearing deficits, developmental delay, mental retardation, hypotonia, seizures, and brain anomalies. Brain anomalies in patients with 1p36 deletion are frequent but inconsistent. To date, 2 cases with monosomy 1p36 associated with periventricular nodular heterotopia (PNH) have been reported. We report a 2-month-old boy with multiple congenital anomalies; brain magnetic resonance imaging revealed PNH. The first 2 described cases were pure terminal deletions, whereas our patient carried unbalanced translocation due to an adjacent 1 segregation of a balanced maternal translocation, resulting in monosomy 1p36.3 and trisomy 19p13.3 identified by whole-genome array comparative genomic hybridization analysis. Our patient, with a smaller deletion that the 2 previously reported cases, can help narrow the critical region for PNH in association with the 1p36 deletion. Several potential candidate genes are discussed.

Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1.

Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal-recessive disorder resulting from mutations in one of three peroxisomal genes essential for ether lipid biosynthesis, PEX7 (RCDP1), GNPAT (RCDP2), and AGPS (RCDP3). Affected patients have characteristic features including shortening of the proximal long bones, epiphyseal stippling, bilateral cataracts, growth and developmental delays. Whereas the majority of patients have RCDP type 1, around 5% have RCDP type 2 or 3. We identified a patient with RCDP type 2 and an apparent homozygous deletion, c.1428delC, after full sequencing of his GNPAT genes. The father was heterozygous for this mutation, while sequencing of the maternal GNPAT genes revealed only wild-type sequence. Southern analyses performed on parental gDNA did not show evidence of a maternal gene deletion. Amplification and fragment analysis of dinucleotide repeat markers spanning chromosome 1 in the patient and both parents revealed paternal uniparental inheritance. We discuss the potential mechanisms causing uniparental disomy (UPD) in this patient and review the literature on chromosome 1 UPD. The absence of non-RCDP clinical features in this patient was consistent with previous literature supporting the absence of imprinted genes on chromosome 1. This first description of RCDP caused by UPD dramatically changes the parental recurrence risk, highlighting the value of obtaining parental genotypes when the proband has a putative homozygous mutation by sequence analysis.

The multidisciplinary evaluation and management of cleft lip and palate.

Cleft lip with or without a cleft palate (CLP) and cleft palate alone (CPA) are common birth defects, with a combined birth prevalence of about 1 to 2/1,000. Affected children have a number of medical issues and potential complications, and therefore require a wide variety of healthcare specialists beyond plastic surgeons and dental specialists. For this reason, the best environment in which to deliver this care is a multidisciplinary cleft clinic (MCC) that features a team of healthcare providers, including audiology, pediatric otolaryngology, speech pathology, occupational/feeding therapy, and genetics. In this setting, the many medical issues that these children face are comprehensively addressed in the most convenient manner, as all the specialists can be seen in a single busy day. Furthermore, the referring primary care provider (PCP) will receive a concise letter that documents the team evaluation, including future management plans and recommendations for therapy. Unfortunately, few papers are available in the literature that review the workings of these clinics. In this paper we will provide such an overview, discussing the management issues for children with CLP/CPA, and how these are addressed by members of the MCC.

Clefting, amniotic bands, and polydactyly: a distinct phenotype that supports an intrinsic mechanism for amniotic band sequence.

Amniotic band sequence (ABS) is a well-described condition involving a variety of congenital anomalies in association with fibrous bands. However, many cases are associated with birth defects that are not readily explained by the mechanism of fibrous strings entangling body parts and causing disruption of the fetal structures. The most common of these is typical cleft lip and palate (CLP). Here we describe such a case, with typical ABS limb defects and constriction bands, along with CLP, supernumerary left nipple, polydactyly, and a skin papilla. This case is nearly identical to a child previously described by Guion-Almieda and Richieri-Costa [2000] and may, therefore, represent a previously unrecognized syndrome that overlaps with ABS. Furthermore it may be that cases with ABS-like anomalies associated with CLP represent a different condition, possibly caused by mutations in the genes Disorganization, p63, or IRF6.