This condition is also known as the Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or postaxial acrofacial dystosis (POADS). The incidence of this condition is not known but it is considered extremely rare. Nothing is presently known of its pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

.

History

This condition was first described by in 1969 by Genée who assumed the condition to be an extreme form of dysostosis mandibulofacialis Wiedemann in 1975 described it as a separate entity. Further cases were reported by Wildervanck in 1975 and by Miller et al in 1979 The syndrome was named the Genée-Wiedemann syndrome in 1987

Genomics

The gene responsible for this disorder is DHODH located at chromosome 16q22. This gene encodes an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 - dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It converts dihydroorotate to orotate:...

 - which catalyses the ubiquinone-mediated oxidation of dihydroorotate to orotate, the fourth enzymatic step in de novo pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

 biosynthesis. The protein is normally located on the outer surface of the inner mitochondrial membrane.

Genetics

A mutation in this gene was reported by Morgan in 1910 in the fruit fly Drosophila melanogaster

Drosophila melanogaster

Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

. In the fly this mutations is characterized by wing anomalies, defective oogenesis

Oogenesis

Oogenesis, ovogenesis or oögenesis is the creation of an ovum . It is the female form of gametogenesis. The male equivalent is spermatogenesis...

, as well as malformed posterior legs.

Clinical

The syndrome consists of severe micrognathia, cleft lip and/or palate

Palate

The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...

, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma

Coloboma

A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid or optic disc...

 of the eyelids and supernumerary nipple

Nipple

In its most general form, a nipple is a structure from which a fluid emanates. More specifically, it is the projection on the breasts or udder of a mammal by which breast milk is delivered to a mother's young. In this sense, it is often called a teat, especially when referring to non-humans, and...

s. Additional features of the syndrome include
downward slanting palpebral fissures, malar hypoplasia, malformed ear

Ear

The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....

s and a broad nasal ridge. Other features include supernumerary vertebrae and other vertebral segmentation and rib

Rib

In vertebrate anatomy, ribs are the long curved bones which form the rib cage. In most vertebrates, ribs surround the chest, enabling the lungs to expand and thus facilitate breathing by expanding the chest cavity. They serve to protect the lungs, heart, and other internal organs of the thorax...

 defects, heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

 defects (patent ductus arteriosus

Patent ductus arteriosus

Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...

, ventricular septal defect

Ventricular septal defect

A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...

, ossium primum and endocardial cushion defect), lung

Lung

The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

 disease from chronic infection

Infection

An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

, single umbilical artery

Artery

Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....

, absence of the hemidiaphragm, hypoplasia of the femora, ossification defects of the ischium and pubis

Pubis

Pubis may refer to:* Pubis * Mons pubis, a padding of fat that protects the pubis bone...

, bilobed tongue

Tongue

The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...

, lung hypoplasia and renal reflux.

The differential diagnosis includes Treacher Collins syndrome

Treacher Collins syndrome

Treacher Collins syndrome , also known as Treacher Collins–Franceschetti syndrome, or mandibulofacial dysostosis is a rare autosomal dominant congenital disorder characterized by craniofacial deformities, such as absent cheekbones. Treacher Collins syndrome is found in about 1 in 10,000 births, ....

, Nager acrofacial dysostosis

Nager acrofacial dysostosis

Nager acrofacial dysostosis is a congenital anomaly syndrome that may be characterized by accessory tragi.Nager Syndrome displays several or all of the following characteristics: underdevelopment of the cheek and jaw area, down-sloping of the opening of the eyes, lack or absence of the lower...

(pre axial cranial dysostosis). Other types of axial cranial dysostosis included the Kelly, Reynolds, Arens (Tel Aviv), Rodríguez (Madrid), Richieri-Costa and Patterson-Stevenson-Fontaine forms.