Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype-phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions.

Pyloric atresia associated with Dieulafoy lesion and gastric dysmotility in a neonate.

In this case study, we report a male infant with pyloric atresia, extreme gastric distension, and a caliber-persistent gastric artery (Dieulafoy lesion) with massive gastric bleeding. After a transverse pyloroplasty and endoscopic hemoclip application to the caliber-persistent gastric artery, very slow gastric emptying developed, which required repeated surgical interventions. Gastroduodenostomy failed to promote gastric emptying. The intraoperative and postmortem histologic examinations of the gastric wall revealed a loss of interstitial cells of Cajal, which possibly explains the extreme motility disorder.

In utero incarceration of congenital diaphragmatic hernia.

In utero diagnosis of incarcerated congenital diaphragmatic hernia has never been reported. In our case, congenital diaphragmatic hernia presented at 34 weeks of gestation with dilated bowel loops, pleural effusion, and ascites on fetal ultrasound. Preterm delivery and emergency exploration revealed a tight posterolateral diaphragmatic defect with extensive bowel infarction.