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Abstract: VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000 –35,000 births, is a non-random association of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), were found to harbor deletions or mutations affecting FOXF1 and the FOX gene cluster on chromosome 16q24. We investigated this gene through direct sequencing and high-density SNP microarray in 12 patients with VACTERL association but without ACD/MPV. Our mutational analysis of FOXF1 showed normal sequences and no genomic imbalances affecting the FOX gene cluster on chromosome 16q24 in the studied patients. Possible explanations for these results include the etiologic and clinical heterogeneity of VACTERL association, the possibility that mutations affecting this gene may occur only in more severely affected individuals, and insufficient study sample size. [Copyright &y& Elsevier]

Abstract: VACTERL association involves the presence of specific congenital, multi-organ malformations that tend to co-occur. Clinical and research efforts typically center on pediatric patients, and there is a scarcity of information in the literature regarding VACTERL-related issues and outcomes in adulthood. We describe here 11 adults with features of VACTERL association ascertained through our research study on the condition. In our cohort of adult patients, approximately 25% of medically significant malformations that are component features of VACTERL association, including 40% of vertebral, 50% of cardiac, and 50% of renal anomalies, were not identified during childhood. Additionally, medical sequelae of many of the primary malformations identified in infancy or early childhood persist or are first reported in adulthood. These sequelae can involve challenging medical and surgical management in adulthood. As most adults with VACTERL association are not specifically followed for VACTERL-related issues, a more uniform diagnostic work-up and a low threshold for investigation of medical sequelae of the primary disorder may enhance the quality of clinical management in these patients. [Copyright &y& Elsevier]

Abstract: We report on the first case of a child with a de novo 7q terminal deletion [46,XX,del(7)(q35 → qter)] presenting esophageal stenosis. This cytogenetic abnormality was confirmed by FISH, using subtelomeric probes, and by a whole-genome array-CGH assay. The child also had phenotypic features previously described in patients with a similar deletion, as growth retardation, microcephaly, coloboma of papilla, ptosis, hearing loss, urinary tract anomalies, partial agenesis of sacrum, hypotonia and neuropsychomotor delay. The odontoid hypoplasia identified, in similarity with the esophageal stenosis, represents an uncommon finding. This report is also the first clinical description of a patient with an abnormality involving the sonic hedgehog gene and an esophageal alteration. It is discussed the possibility of a specific association between them, according to some results observed in studies with animal models. [ABSTRACT FROM AUTHOR]

Abstract: Patients with congenital anorectal malformations (ARM) often have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalences at birth of associated malformations in patients of a geographically defined population with ARM which were collected between 1979 and 2003 in 334, 262 consecutive births. Of the 174 patients with ARM during the study period, 49.4% had associated malformations. Patients with associated malformations were further classified into groups with nonsyndromic multiple congenital anomalies; chromosomal abnormalities; nonchromosomal syndromes including Townes–Brocks, Walker–Warburg, Ivemark, Fetal alcohol, Klippel–Feil, Pallister–Hall, Facio-auriculo-vertebral spectrum, deletion 22q11.2; sequences, including OEIS, Pierre Robin and sirenomelia; and associations including VATER and MURCS. Malformations of the urogenital system (81.1%) and of the skeletal system (45.5%) were the most common other congenital anomalies occurring with ARM in multiply malformed patients without recognized entities, followed by malformations of the cardiovascular system, the digestive system, and the central nervous system. Weight, length, and head circumference of children with ARM and multiple associated malformations were lower than in controls, as was the weight of the placenta. Prenatal detection by fetal ultrasonographic examination was rarely made in isolated ARM. However, even in multiple associated malformations, prenatal detection by fetal ultrasonographic examination had a low sensitivity, 36%. In conclusion the overall prevalence of malformations, which was close to 1 in two infants, emphasizes the need for a thorough investigation of patients with ARM. A routine screening for other malformations may be considered in patients with ARM, and genetic counseling seems warranted in most of these complicated cases. [Copyright &y& Elsevier]

Mabry syndrome is a glycophosphatidylinositol (GPI) deficiency characterized by intellectual disability, distinctive facial features, intractable seizures, and hyperphosphatasia. We expand the phenotypic spectrum of inherited GPI deficiencies with novel bi-allelic phosphatidylinositol glycan anchor biosynthesis class O (PIGO) variants in a neonate who presented with intractable epilepsy and complex gastrointestinal and urogenital malformations. [ABSTRACT FROM AUTHOR]