periorbital fullness

Gabriele-de Vries Syndrome

Clinical Characteristics
Ocular Features: 

A number of nondiagnostic signs occur in the periocular structures as part of the general facial dysmorphism.  There is a general fullness to the periocular area, most evident in the upper eyelids.  The lid fissures slant downward and the eyebrows are sparse.  Strabismus is often present.  Ptosis has been noted in a few individuals.

Systemic Features: 

Systemic signs are inconsistent and highly variable.  Intrauterine growth is usually below average.  Feeding problems are evident from birth.  The facial dysmorphology is highlighted by a high, broad forehead and accentuated by micrognathia and midface hypoplasia.  The ears are posteriorly rotated.  General development is delayed and milestones, if achieved, are delayed.  Behavioral problems can be manifest as anxiety and some individuals have features of the autism spectrum.  Abnormal movements such as tremor and dystonia are sometimes present.

Brain imaging may reveal delayed myelination, frontal gliosis, white matter abnormalities, and enlarged ventricles.

Genetics

Heterozygous mutations in the YY1 gene (14q32) have been identified in this condition.  The gene is a transcription factor that acts both as a repressor and an activator in specific circumstances.  Virtually all cases occur de novo.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective generalized treatment has been reported.

References
Article Title: 

YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction

Gabriele M, Vulto-van Silfhout AT, Germain PL, Vitriolo A, Kumar R, Douglas E, Haan E, Kosaki K, Takenouchi T, Rauch A, Steindl K, Frengen E, Misceo D, Pedurupillay CRJ, Stromme P, Rosenfeld JA, Shao Y, Craigen WJ, Schaaf CP, Rodriguez-Buritica D, Farach L, Friedman J, Thulin P, McLean SD, Nugent KM, Morton J, Nicholl J, Andrieux J, Stray-Pedersen A, Chambon P, Patrier S, Lynch SA, Kjaergaard S, Torring PM, Brasch-Andersen C, Ronan A, van Haeringen A, Anderson PJ, Powis Z, Brunner HG, Pfundt R, Schuurs-Hoeijmakers JHM, van Bon BWM, Lelieveld S, Gilissen C, Nillesen WM, Vissers LELM, Gecz J, Koolen DA, Testa G, de Vries BBA. YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction. Am J Hum Genet. 2017 Jun 1;100(6):907-925.

PubMed ID: 
28575647

Williams Syndrome

Clinical Characteristics
Ocular Features: 

Blue irides (77%) and a lacey or stellate pattern (74%) of the iris are characteristic.  The stroma appears coarse with radial or cartwheel striations.  The iris collarette is usually absent or anomalous.  Features of the Peters' anomaly may be present.  The periorbital tissues are described as 'full' and prominent.  Strabismus (usually esotropia) occurs in more than half of patients.  Retinal vessel tortuosity is present in 22% of patients.  Cataracts may be found in younger individuals but are uncommon. Hyperopia is the most common refractive error.  Keratoconus has been described in at least 3 patients.

Systemic Features: 

The phenotype is variable, likely depending upon the size of the deletion.  Cardiovascular disease, primarily hypertension and large vessel stenosis, are among the most important features.  The elastin arteriopathy lead to thickened arterial walls with peripheral pulmonary stenosis and supravalvular aortic stenosis.  The facies is considered unique with bitemporal narrowing, a wide mouth, full lips, malocclusion, small jaw, and prominent earlobes.  The teeth are small and widely spaced.  Connective tissue abnormalities include joint hyperextensibility, hernias, lax skin, hypotonia, and bowel/bladder diverticulae.  Small birth size is common and infants often fail to thrive but at puberty patients can experience a growth spurt.  Ultimate height in adults is usually in the third centile.

Vocal cord anomalies and paralysis can result in a hoarse voice.  A sensorineural hearing loss is common among adults but hyperacusis is often present in young children.

Hypercalcemia and hypercalciuria are common and some (10%) have hypothyroidism.

Most individuals have some cognition difficulties and delays but normal intelligence has also been reported.  Patient personalities consist of anxiety, attention deficit disorder, marked friendliness and a high level of empathy.  Visiospatial construction is often impaired.  Most adults are unable to live independently.

Genetics

This is a deletion syndrome but included in this database because the major features are due to the loss of a single gene (ELN).  The deletion segment consists of 1.4-1.8 Mb at 7q11.23 containing as many as 28 genes.   Most cases occur sporadically but parent-child transmission and affected siblings have been reported.  The recurrence risk is low.

Increased tortuosity of the retinal arterioles is also a feature of Fabry disease (301500) and of a condition known as isolated retinal arteriolar tortuosity (611773, 180000).

Treatment
Treatment Options: 

Feeding issues should be addressed early in infants who fail to thrive.  Early intervention with speech and physical therapy plus special education can be helpful.  Psychological evaluations may help in managing behavioral issues.

Hypertension can often be managed medically but surgery may be required for vascular stenoses.   Hypercalcemia and hypothyroidism often respond to medical therapy. Strabismus, vessel narrowing, and valvular malfunctions can be treated surgically.

References
Article Title: 

The iris in Williams syndrome

Holmstrom G, Almond G, Temple K, Taylor D, Baraitser M. The iris in Williams syndrome. Arch Dis Child. 1990 Sep;65(9):987-9.

PubMed ID: 
2221973

Ocular findings of Williams' syndrome

Hotta Y, Kishishita H, Wakita M, Inagaki Y, Momose T, Kato K. Ocular findings of Williams' syndrome. Acta Paediatr Scand. 1990 Aug-Sep;79(8-9):869-70.

PubMed ID: 
2239289
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