Chromosome 1p36.22p36.21 duplications/triplication causes Setleis syndrome (focal facial dermal dysplasia type III).

Focal facial dermal dysplasias (FFDD) are characterized by congenital bitemporal or preauricular atrophic skin lesions, and either autosomal dominant or autosomal recessive inheritance. Setleis syndrome (SS), FFDD type III, is a severe form of FFDD with the ectodermal lesions plus other striking facial features. Autosomal recessive nonsense and frameshift mutations in TWIST2 have been found to cause SS in some but not all individuals.

Advancing our understanding of the inheritance and transmission of pectus excavatum.

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder.

Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene.

Fibrochondrogenesis is a severe, autosomal-recessive, short-limbed skeletal dysplasia. In a single case of fibrochondrogenesis, whole-genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions. Because of the predominantly skeletal nature of the phenotype, the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage-selective genes via the UCLA Gene Expression Tool, UGET.

Avoiding transmitting identified mutations to offspring using preimplantation genetic diagnosis.

Background: Preimplantation genetic diagnosis has been used to decrease or avoid the risk of transmitting identified mutations to offspring.

Case: A 29-year-old woman with spondyloepiphyseal dysplasia congenita and her 30-year-old husband with Marfan syndrome underwent in vitro fertilization with preimplantation genetic diagnosis. Two mutation-negative embryos were transferred into a gestational carrier, who became pregnant with twins and delivered two clinically normal neonates.

Polyhydramnios, fetal overgrowth, and macrocephaly: prenatal ultrasound findings of Costello syndrome.

Costello syndrome is a multiple congenital anomaly syndrome consisting of dysmorphic facies, cutis laxa, short stature, developmental delay, and mental retardation. Complications include failure to thrive, hypertrophic cardiomyopathy with arrhythmias, and benign and malignant tumors. This report describes a new case of Costello syndrome in a preterm infant born at 27 weeks gestation and diagnosed with Costello syndrome at 7 weeks of life who died at 6 months of age due to cardiac and pulmonary complications.

Hardikar syndrome: new features.

Hardikar syndrome (HS) is a disorder of multiple anomalies predominantly characterized by cleft lip/palate, liver and biliary tract disease, intestinal malrotation, obstructive uropathy, and retinopathy. To date, three patients have been reported with the unusual constellation of chronic liver/biliary tract disease and obvious defects in organogenesis [Hardikar et al. (1992): Am J Med Genet 44: 13-17; Cools and Jaeken (1997): Am J Med Genet 71: 472-474].

Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8.

Trismus-pseudocamptodactyly syndrome (TPS) is a rare autosomal dominant distal arthrogryposis (DA) characterized by an inability to open the mouth fully (trismus) and an unusual camptodactyly of the fingers that is apparent only upon dorsiflexion of the wrist (i.e., pseudocamptodactyly).

Family study of the inheritance of pectus excavatum.

Background: The most common congenital deformity of the chest wall is pectus excavatum, a malformation that is present in between 1 in 400 and 1 in 1000 live births and causes the body of the sternum to be displaced, producing a depression. There are many different shapes of the pectus, and multiple factors probably contribute to the final form. The etiology of pectus excavatum is uncertain, but a familial tendency has been found in clinical experience, where it may be seen in more than one sibling.

Classification of the dysmorphology of pectus excavatum.

Background/purpose: To describe the dysmorphology of pectus excavatum, the most common congenital chest wall anomaly.

Methods: A stratified sample of 64 patients, representative of a patient population with pectus excavatum of the Children's Hospital of King's Daughters in Norfolk, VA, was described and classified. The sample was stratified by sex to represent a 4:1 male-to-female ratio.

Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation.

We recently identified mutations of ARX in nine genotypic males with X-linked lissencephaly with abnormal genitalia (XLAG), and in several female relatives with isolated agenesis of the corpus callosum (ACC). We now report 13 novel and two recurrent mutations of ARX, and one nucleotide change of uncertain significance in 20 genotypic males from 16 families. Most had XLAG, but two had hydranencephaly and abnormal genitalia, and three males from one family had Proud syndrome or ACC with abnormal genitalia.

Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia.

Fanconi anemia is an inherited disease characterized by bone marrow failure, congenital malformations, and predisposition to cancer. The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1). We examined four kindreds afflicted with Fanconi anemia for the presence of germline BRCA2 mutations.

Early childhood hearing loss: clinical and molecular genetics. An educational slide set of the American College of Medical Genetics.

An educational slide set entitled "Early Childhood Hearing Loss: Clinical and Molecular Genetics" is offered by the American College of Medical Genetics (ACMG). The slide set is produced in Microsoft PowerPoint 2002. It is extensively illustrated and supported with teaching tools, explanations of each slide and figure, links to Internet resources, and a bibliography.

Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features.

Background: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling.

Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.

Russell-Silver syndrome (RSS) is a form of congenital short stature characterized by severe growth retardation and variable dysmorphic features. In some RSS individuals, alterations in imprinted genes may be involved because approximately 7% of sporadic patients have been observed to have maternal uniparental disomy (mUPD) of chromosome 7. RSS patients with structural abnormalities of chromosome 7 have also been described.