tented upper lip

Basel-Vanagaite-Smirin-Yosef Syndrome

Clinical Characteristics
Ocular Features: 

The eyes appear abnormally far apart.  Ptosis, microcornea, congenital cataracts, sparse eyebrows, and strabismus are usually present.  Epicanthal folds are often seen.

Systemic Features: 

Psychomotor development is severely delayed and with delay or absence of milestones.  DTRs are often hyperactive but some infants are described as hypotonic.  Some individuals have seizures.  There may be a nevus flammeus simplex lesion on the forehead and body hair is sparse.  Cleft palate, cardiac septal defects, hypospadius, thin corpus callosum and cerebral ventricular dilation have been observed.  The upper lip may have a tented morphology with everted lower lip vermilion. A short philtrum is common. 

Genetics

A homozygous missense mutation in the MED25 gene (19q13.33) has been reported and the transmission pattern is consistent with autosomal recessive inheritance.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No known treatment has been reported.

References
Article Title: 

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

Basel-Vanagaite L, Smirin-Yosef P, Essakow JL, Tzur S, Lagovsky I, Maya I, Pasmanik-Chor M, Yeheskel A, Konen O, Orenstein N, Weisz Hubshman M, Drasinover V, Magal N, Peretz Amit G, Zalzstein Y, Zeharia A, Shohat M, Straussberg R, Monte D, Salmon-Divon M, Behar DM. Homozygous MED25 mutation implicated in eye-intellectual disability syndrome. Hum Genet. 2015 Jun;134(6):577-87.

PubMed ID: 
25792360

PEHO Syndrome

Clinical Characteristics
Ocular Features: 

Optic atrophy is a common feature.  There may be lack of visual fixation from birth or sometimes several months later, attributed to cortical inattention.  Flash visual evoked potentials may be unrecordable. Pupillary responses to light are 'weak' and sluggish. Epicanthal folds may be seen.

Systemic Features: 

Infants are usually born with a normal head circumference but fall behind (2 SD or more) in the first year.  They have neonatal and infantile central hypotonia with brisk peripheral tendon reflexes during early childhood.  They are sometimes described as drowsy or lethargic.  Facial and limb edema can be extensive but transient sometimes and can disappear later in childhood.  The fingers are tapered.  The cheeks are full, the mouth is usually open and the upper lip appears 'tented'.  Global developmental delay is common and normal milestones are seldom attained.  Some patients have been described as severely retarded mentally.  Infantile spasms and myoclonic jerkingcan be seen within the first months of life while frank seizures with hypsarrhythmia are common in the first year of life.  Status epilepticus is a common occurrence.  General drowsiness and poor feeding are often features.  Death usually occurs in infancy or early childhood.  Midface hypoplasia and micrognathia are often present.

Brain imaging (MRI) and histology show severe alterations in myelination and cellular organization.  Neuronal loss is seen in the inner granular layer of the cerebellum but there is relative preservation of Purkinje cells.  General and progressive atrophy of the cerebellum and brain stem have been described.

Genetics

Homozygous frameshift mutations in ZNHIT3 (17q12) have been identified in affected members of several consanguineous families.  The presumed mutation seems to be most prevalent in Finland.

A somewhat similar disorder known as PEHO-like syndrome (617507) is the result of homozygous mutations in the CCDC88A gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Physical therapy to prevent contractures and general supportive care can be helpful.  Supplemental feeding may be required. 

References
Article Title: 

The PEHO syndrome

Riikonen R. The PEHO syndrome. Brain Dev. 2001 Nov;23(7):765-9. Review.

PubMed ID: 
11701291
Subscribe to RSS - tented upper lip