American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP–HHT was described that is also caused by mutations in SMAD4. Although both JP and JP–HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all...
Several duplications of chromosome 21q helped to narrow down the Down syndrome (DS) critical region (DSCR) to chromosomal band 21q22 with an approximate length of 5.4 Mb. Recently, it has been suggested that the facial gestalt of DS has been linked to the distal part of the DSCR whereas the proximal region harboring DSCR1/RCAN and DSCAM should be associated with the cardiac abnormalities. Here, we...
Aortic aneurysm and dissection cause significant morbidity and mortality. There are several known single gene disorders that predispose to isolated aortic disease and eventually aneurysm and dissection. FBN1 mutations are associated with multiple clinical phenotypes, including Marfan syndrome (MFS), MASS phenotype, and familial ectopia lentis, but rarely with isolated aortic aneurysm and dissection...
The recent series of articles describing human surface anatomy included an article on the ear by Hunter et al. [Hunter et al. (2009); Am J Med Genet Part A 149A: 40–60]. That publication did not include the incisura. This article provides an approach to assessing the incisura in the hope that others may find it useful and/or modify it as appropriate. © 2010 Wiley‐Liss, Inc.
The facial anomalies associated with fetal alcohol syndrome (FAS), some of which are also present in individuals with less severe forms of the broader category of fetal alcohol spectrum disorders (FASD), are typically identified with the aid of linear distance measurements taken between facial landmarks. Digital facial imaging methods are increasingly being used in syndrome delineation. Distance measurements...
Weaver syndrome comprises pre‐ and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance and developmental delay; it is a generally sporadic disorder, although autosomal dominant inheritance has been reported. Some of the manifestations characterize both the Weaver and Sotos syndrome, and distinction between the two is mainly by clinical examination and molecular...
Loeys–Dietz Syndrome (LDS) is an autosomal dominant aortic aneurysm syndrome with multisystem involvement, caused by heterozygous mutations of transforming growth factor β receptor type 1 (TGFBR1) or type 2 (TGFBR2) genes. We report on a neonate with the disorder caused by a known TGFBR2 mutation, who developed neonatal‐onset progressive dilation of the aortic valve and aneurysms of the aortic root...
Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought...
Mutations in the FGD1 gene have been shown to cause Aarskog–Scott syndrome (AAS), or facio‐digito‐genital dysplasia (OMIM#305400), an X‐linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed...
Diagnosing the specific type of severe intrauterine growth restriction (IUGR) that also has post‐birth growth restriction is often difficult. Eight relatively common syndromes are discussed identifying their unique distinguishing features, overlapping features, and those features common to all eight syndromes. Many of these signs take a few years to develop and the lifetime natural history of the...
Presented here is a young girl with a rare interstitial duplication of 8q23.3‐q24.21. At birth, unusual facial features led to karyotype analysis with a finding of increased material in 8q. Specific determination of where the extra material came from required comparative genomic hybridization (CGH). The affected girl has dysmorphic facial features including hypertelorism, a wide nasal bridge, retrognathia,...
The 3p deletion syndrome is a rare disorder caused by deletions of different sizes in the 3p25‐pter region. It is characterized by growth retardation, developmental delay, mental retardation, dysmorphism, microcephaly, and ptosis. The phenotype of individuals with deletions varies from normal to severe. Most cases occur de novo, but a few familial cases have been reported. We describe two families...
Russell–Silver syndrome (RSS) is a heterogeneous disorder associated with pre‐ and post‐natal growth restriction and relative macrocephaly. Involvement of imprinted genes on both chromosome 7 and 11p15.5 has been reported. To further characterize the role of epimutations in RSS we evaluated the methylation status at both 11p15.5 imprinting control regions (ICRs): ICR1 associated with H19/IGF2 expression...
Duplications involving portions of the long arm of the X‐chromosome can be associated with mental retardation, short stature, microcephaly, panhypopituitarism, and a wide range of physical findings. Less common are duplications in distal Xq associated with hemihyperplasia and digital anomalies. We report on a 4‐year‐old female with hemihyperplasia, syndactyly of fingers and toes, bilateral 5th finger...
Congenital pancreatic hypoplasia is a rare cause of neonatal diabetes. We report on a series of three patients with pancreatic agenesis and congenital heart defects. All had abdominal scan evidence of pancreatic agenesis. In addition, Patient 1 had a ventricular septal defect, patent ductus arteriosus and pulmonary artery stenosis; Patient 2 had a truncus arteriosus and Patient 3 had tetralogy of...