OMIM ID:
Setleis Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The eyebrows slant upward and the lashes may be absent or appear in double rows as in distichiasis. The periorbital skin can appear 'puckered with puffiness'. The palpebral fissures appear short in some individuals.
Systemic Features
This condition is associated with a variety of facial skin anomalies. The overall facial appearance has been described as 'leonine". The facial skin often has some redundancy with a rubbery feel and may appear ‘puffy’ or wrinkled and puckered about the eyes. The lips are large. The overall appearance has been described as 'leonine'. The nasal ridge can be flat and the nose can have a bulbous tip. The teeth may be conical in shape.
Genetics
Inheritance
The genetic basis for this disorder seems to lie in heterozygous mutations in the TWIST2 gene (2q37.3). Parent to child transmission has also been reported for some features but the signs in parents may be subtle..
The TWIST2 mutation was not present in several unrelated probands suggesting there is some genetic heterogeneity. Further, Brauer syndrome (136500) (focal facial dermal dysplasia or FFDD type I) is clinically somewhat similar to Setleis syndrome with respect to the distribution and nature of facial skin lesions and it has been suggested that the two disorders may be one and the same. The gene responsible for Brauer syndrome has not been found but the condition is inherited in autosomal dominant fashion. It is possible therefore that families labeled Setleis with an AD pattern of transmission actually have Brauer syndrome. It should also be noted that the ablepharon-macrostonia syndrome (200110) and Barber-Say syndrome (209885) are also caused by mutations in TWIST2 and have some features in common with Setleis syndrome.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.