redundant skin

Barber-Say Syndrome

Clinical Characteristics
Ocular Features: 

The ocular features consist mainly of skin changes in the lids including hyperlaxity and redundancy.  There may be ectropion of the lower eyelids and sparsity of the eyebrows.  Some evidence of micro- or ablepharon is often present.  Hypertelorism and exophthalmia have been described.

Systemic Features: 

Multiple external congenital anomalies are present at birth including skin laxity, hypertrichosis (especially of the forehead, neck and back), and low-set and malformed pinnae.  Macrostomia and thin lips with redundant facial skin are often evident.  The nose appears bulbous.  The thoracic skin can be atrophic and the nipples may be hypoplastic.  Hypospadias has been reported.  A highly arched or cleft palate may be present and some individuals have a conductive hearing loss.  The teeth are small and eruption may be delayed.  Cognitive deficits may be present and mental retardation has been reported. 

Genetics

Based on genotyping and the limited number of reported pedigrees, inheritance most likely follows an autosomal dominant pattern.  Direct parent to child transmission has been reported.  Detailed examination of parents sometimes reveals mild features that are easily missed.  Mutations in the TWIST2 gene have been found in 10 unrelated individuals with Barber-Say syndrome.

TWIST2 mutations have also been found in Setleis syndrome (227260) and in ablepharon-macrostomia syndrome (200110).  These conditions have some clinical features in common with Barber-Say syndrome.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no known treatment for this disorder but correction of selected anomalies such as ectropion and cleft palate may be indicated.

References
Article Title: 

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes

Marchegiani S, Davis T, Tessadori F, van Haaften G, Brancati F, Hoischen A, Huang H, Valkanas E, Pusey B, Schanze D, Venselaar H, Vulto-van Silfhout AT, Wolfe LA, Tifft CJ, Zerfas PM, Zambruno G, Kariminejad A, Sabbagh-Kermani F, Lee J, Tsokos MG, Lee CC, Ferraz V, da Silva EM, Stevens CA, Roche N, Bartsch O, Farndon P, Bermejo-Sanchez E, Brooks BP, Maduro V, Dallapiccola B, Ramos FJ, Chung HY, Le Caignec C, Martins F, Jacyk WK, Mazzanti L, Brunner HG, Bakkers J, Lin S, Malicdan MC, Boerkoel CF, Gahl WA, de Vries BB, van Haelst MM, Zenker M, Markello TC. Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes. Am J Hum Genet. 2015 Jul 2;97(1):99-110.

PubMed ID: 
26119818

Pseudoxanthoma Elasticum

Clinical Characteristics
Ocular Features: 

Breaks in Bruch membrane lead to the classic non-diagnostic ocular sign in this disease known as angioid streaks.  These are typically bilateral, reddish-brown curvilinear bands that vaguely resemble a vascular pattern seen most commonly in the posterior pole radiating from the peripapillary area.  They typically have their onset after the skin lesions appear.  The fundus may also have areas of yellow mottling temporal to the fovea suggestive of an orange peel surface.  These are sometimes labeled 'peau d'orange' and their appearance frequently precedes the appearance of angioid streaks.  Optic disc drusen are said to occur 20-50 times more frequently than in the general population and may be apparent before the appearance of angioid streaks.  A significant proportion of patients have atrophy of the RPE and outer retina, especially those with early onset and rapid progression of the disease.

The major threat to vision comes from the formation of subretinal neovascular nets which often bleed resulting in secondary scarring and fibrosis.  These frequently involve the central macula which is why central vision is primarily impacted and peripheral vision usually remains normal.  Macular involvement is evident at a mean age of 44 years and the majority of patients are visually handicapped by the age of 52 years.

Systemic Features: 

The skin has characteristic changes of several types due to defective elastin.  It is often lax and redundant with localized plaques of hyperkeratotic papules giving the typical 'plucked chicken' appearance.  The latter are typically seen in the skin of the neck, in inguinal folds and in the popliteal and antecubital spaces.  These may have their onset in childhood but sometimes later.  They are generally asymptomatic and primarily of cosmetic importance.  The oral, rectal, and vaginal mucosa may also be involved.  Focal deposits of calcium are often seen.

Vascular disease secondary to calcification of elastic media and intima are responsible for the major health problems in this disease but they usually are not evident until later in life.  Hemorrhage or occlusion often results.  At least 10% of individuals with this disease experience a gastrointestinal hemorrhage at some point in their lives and this can be life-threatening.  Intermittent claudication can be incapacitating.  Coronary artery disease is frequently a symptom.  Occlusive disease of the renal arteries can result in hypertension.  Malfunction of heart valves, especially the mitral valve, is common.

Genetics

This is an autosomal recessive disorder caused by mutations in the ABCC6 gene (16p13.1).  Females are affected nearly twice as often as males.  Some heterozygotes have minor manifestations of the disease but the full clinical picture is only seen in homozygotes.

Rare variant mutations in the ABCC6 gene may cause typical ocular changes without systemic manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Choroidal neovascularization should be treated.  Intravitreal injections of ranibizumab may be beneficial as a prophylactic measure for the preservation of central vision.  GI bleeds require prompt and vigorous treatment and cardiac valves sometimes require repair.  Redundant skin can be surgically removed.  Patients should avoid contact sports and activities requiring heavy lifting or straining.  Antibiotic prophylaxis should be considered for patients with heart valve disease before undergoing procedures.

References
Article Title: 
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