periocular skin tags

Encephalocraniocutaneous Lipomatosis

Clinical Characteristics
Ocular Features: 

Ocular choristomas of the periocular tissue such as epibulbar dermoids or lipodermoids are seen in 80% of individuals.  Some degree of microphthalmia, a 'hypertrophic' conjunctiva, and sclerocornea have been reported.  The pupils are small and iris hypoplasia with anterior chamber anomalies has been described.  The macular reflex can be absent and colobomas of the eyelids (and rarely uveal tract) have been seen.

Systemic Features: 

Preauricular skin tags may be present.   Fatty tissue nevi associated with alopecia as well as frontotemporal or zygomatic subcutaneous fatty lipomas, and focal dermal hypoplasia are seen externally in many patients.   Coarctation and/or hypoplasia of the thoracic aorta along with aortic valve anomalies are sometimes present.

Intracranial and intraspinal lipomas are present in over 60% of individuals.  Arachnoid cysts with ventricular enlargement, and leptomeningeal angiomatosis are frequently present.  Jawbone cysts and tumors are common. The skull and heart may also have lipomas.  Seizures and some intellectual disability have been diagnosed in many affected individuals but a third or more have normal intellect.  The affected cortex may calcify later in life.

Genetics

ECCL is considered to result from postzygotic activating mutations in the FGFR1 gene (8p11.23) resulting in a mosaic distribution.  This may help explain the highly variable and widespread distribution of skin and CNS lesions.  A 5-year-old female with an affected father and paternal grandmother have been reported suggesting autosomal dominant inheritance.

Mutations in the same gene have been found in Pfeiffer syndrome (101600).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment for the overall condition but selective removal of tumors with cosmetic and pressure consequences should be considered.

References
Article Title: 

Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis

Bennett JT, Tan TY, Alcantara D, Tetrault M, Timms AE, Jensen D, Collins S, Nowaczyk MJ, Lindhurst MJ, Christensen KM, Braddock SR, Brandling-Bennett H, Hennekam RC, Chung B, Lehman A, Su J, Ng S, Amor DJ; University of Washington Center for Mendelian Genomics; Care4Rare Canada Consortium, Majewski J, Biesecker LG, Boycott KM, Dobyns WB, O'Driscoll M, Moog U, McDonell LM. Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis. Am J Hum Genet. 2016 Mar 3;98(3):579-87.

PubMed ID: 
26942290

Beare-Stevenson Syndrome

Clinical Characteristics
Ocular Features: 

The midface hypoplasia and shallow orbits result in the appearance of prominent eyes.  Ptosis and hypertelorism have been reported while the palpebral fissures are downslanting. One patient has been reported to have optic atrophy.  Another patient was described with cloudy corneas, irregular irides and nonreactive pupils.

Systemic Features: 

Pregnancies may be complicated by polyhydramnios.  Infants are born with craniosynostosis with a cloverleaf pattern usually.  The skull is often shortened in the anteroposterior axis with flattening of the occipital region.  The skin is deeply furrowed with the cutis gyrata patterns most prominent in the posterior scalp but also present on the palms, soles, pinnae, and elsewhere.  Acanthosis nigricans is often present.

There is midface hypoplasia and nearly all individuals have intellectual disability.

The external ear canals can be atretic, the nares are often anteverted, and the mouth may be small.  An excess number of neonatal teeth and hypoplastic nails have been noted.  Hydrocephalus is common.  The umbilical stump is often unusually prominent.  Anogenital anomalies such as an anteriorly placed anus, cryptorchidism, and bifid scrotum may be present.  Pyloric stenosis is sometimes present.

Upper airway obstruction with respiratory distress may necessitate a tracheotomy. A cartilaginous tracheal sleeve replacing the normal C rings of cartilage has been found in several infants. These can be difficult to detect and their presence may have been responsible for breathing restrictions that has led to the demise of some children before two years of age.

Genetics

Reported cases have occurred sporadically.  Increased paternal age has been suggested as a factor in the occurrence of heterozygous mutations in the FGFR2 gene (10q26.13) which have been identified in some individuals.

Other forms of craniosynostosis in which mutations in FGFR2 have been found are: Crouzon Syndrome (123500), Pfeiffer Syndrome (101600), Apert Syndrome (101200), Jackson-Weiss Syndrome (123150), and Saethre-Chotzen Syndrome (101400).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no general treatment for this syndrome.  Several infants have had tracheotomies and CNS shunts.

References
Article Title: 

Beare-Stevenson cutis gyrata syndrome

Hall BD, Cadle RG, Golabi M, Morris CA, Cohen MM Jr. Beare-Stevenson cutis gyrata syndrome. Am J Med Genet. 1992 Sep 1;44(1):82-9. PubMed PMID: 1519658.

PubMed ID: 
1519658
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