dysmorphic facies

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

Congenital Heart Defects, Dysmorphic Facies, and Intellectual Developmental Disorder

Clinical Characteristics
Ocular Features: 

The dysmorphic facial features primarily involve the periocular structures.  These include hypertelorism, ptosis, epicanthal folds, strabismus and upslanted palpebral fissures.

Systemic Features: 

Septal defects involving both the atrium and the ventricle are consistently present.  Pulmonary valve abnormalities are present in some patients.

Posteriorly rotated pinnae and a small mouth with a thin upper lip have been observed.  Camptodactyly and clinodactyly are common.  Some patients have mild microcephaly.

Global developmental delay is a consistent feature manifest as delays in walking and speech and eventual intellectual disability.  Feeding difficulties are common.  Hypotonia and hypermobile joints are often noted.  Imaging of the brain may reveal agenesis of the corpus callosum, incomplete formation of the inferior vermis, and leukomalacia of periventricular tissue.

Genetics

Heterozygous mutations have been identified in the CDK13 gene (7p14.1) in seven unrelated individuals.  Heterozygous parents may not have the full phenotype.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for the generalized condition.

References
Article Title: 

Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing

Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, McRae J, Fitzgerald TW, Singh T, Swaminathan GJ, Prigmore E, Rajan D, Abdul-Khaliq H, Banka S, Bauer UM, Bentham J, Berger F, Bhattacharya S, Bu'Lock F, Canham N, Colgiu IG, Cosgrove C, Cox H, Daehnert I, Daly A, Danesh J, Fryer A, Gewillig M, Hobson E, Hoff K, Homfray T; INTERVAL Study., Kahlert AK, Ketley A, Kramer HH, Lachlan K, Lampe AK, Louw JJ, Manickara AK, Manase D, McCarthy KP, Metcalfe K, Moore C, Newbury-Ecob R, Omer SO, Ouwehand WH, Park SM, Parker MJ, Pickardt T, Pollard MO, Robert L, Roberts DJ, Sambrook J, Setchfield K, Stiller B, Thornborough C, Toka O, Watkins H, Williams D, Wright M, Mital S, Daubeney PE, Keavney B, Goodship J; UK10K Consortium., Abu-Sulaiman RM, Klaassen S, Wright CF, Firth HV, Barrett JC, Devriendt K, FitzPatrick DR, Brook JD; Deciphering Developmental Disorders Study., Hurles ME. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat Genet. 2016 Sep;48(9):1060-5.

PubMed ID: 
27479907
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