hypotrichosis

Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome

Clinical Characteristics
Ocular Features: 

Sparse hair can be noted at birth and by several years of age the alopecia of the eyelids and eyebrows is complete.  The upper eyelids may be swollen at birth as well. 

Systemic Features: 

The facial features are unusual.  The nose appears long and may have a broad nasal root.  The lips are full and the lower jaw is prominent. Evidence of developmental delay has been reported in one patient.

The scrotum can be edematous at birth and sometimes contains large hydroceles.  Hair is sparse in infancy but within a few years alopecia is complete.  Telangiectases on the scalp, scrotum, and limbs are evident at several years of age.  Pulmonary vascular congestion and lymphangiectasia may be present in some individuals antenatally.  Renal failure, sometimes with hypertension can occur at any time from early childhood to young adulthood.  Renal biopsy has shown histologic features consistent with membranoproliferative glomerulonephritis and thrombotic microangiopathy.  This may be preceded by proteinuria in infants as young as 2 years. 

Genetics

This condition is the result of heterozygous mutations in the SOX18 gene (20q13.33). 

Homozygous mutations in the same gene may be responsible for a somewhat similar disorder (HLTS) (607823) which has many of the same facial and systemic features but lacks the renal disease. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Some patients have benefitted from renal transplantation.

References
Article Title: 

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

EEM Syndrome

Clinical Characteristics
Ocular Features: 

Granular pigmentation and a grayish coloration of the retina may be present.  The peripheral retina usually appears normal but the posterior pole and macula have pigmentary changes consisting of clumping and geographic atrophy.  Fluorescein angiography shows patchy areas of hyperfluorescence.  Patients in their 30s have been reported to have normal ERGs in one study.  Reduced acuity can be noted in the first decade but progression is slow.  Acuity levels in the 20/200 range may be seen in the fourth decade of life. 

Systemic Features: 

Ectodermal dysplasia with ectrodactyly and syndactyly are prominent features of this syndrome.  Hypotrichosis of the scalp, eyebrows and eyelashes is often seen.  Partial anodontia and diastema are also features.  Syndactyly of the toes is present more frequently than found among the fingers. 

Genetics

This is an autosomal recessive disorder resulting from mutations in the CDH3 gene (16q22.1).

EEM syndrome is allelic to the Hypotrichosis with Macular Dystrophy syndrome (601553).  However, the latter lacks the dental, limb, and digital anomalies as well as the hypotrichosis of eyebrows and eyelashes.  

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for this disease. 

References
Article Title: 

Hypotrichosis with Juvenile Macular Degeneration

Clinical Characteristics
Ocular Features: 

Macular dystrophy usually becomes symptomatic before the second decade of life but retinal evidence of macular degeneration can be seen in the first decade.   EOG is usually normal while the ERG responses are decreased early and with time decrease further in amplitude.  Pattern reversal VEPs are significantly subnormal even while vision is relatively good.  Visual acuity decreases slowly in spite of significant deterioration of cone- and rod-mediated retinal function.  Retinal pigmentary changes consisting of irregular clumping and areas of hypopigmentation are evident in the macular and perimacular areas and sometimes beyond.  Most patients eventually become blind. 

Systemic Features: 

Scalp hair loss occurs during the first months of life but the alopecia does not affect eyebrows or eyelashes unlike that seen in the EEM disorder (225280)  which in addition has digital and dental anomalies.  Partial regrowth may occur during puberty.  Light and electron microscopy of hair shafts may reveal pili torti, longitudinal ridging with scaling, and fusiform beading but these are not present in all patients. 

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the CDH3 gene located at 16q22.1.

EEM syndrome (225280) is an allelic disorder with similar hair and retinal features plus dental, digital and limb anomalies.  The hypotrichosis also involves the eyebrows and eyelashes in this disorder, however. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no known treatment for this disorder. 

References
Article Title: 

Hallermann-Streiff Syndrome

Clinical Characteristics
Ocular Features: 

Nearly all patients (80+ %) have microphthalmia and bilateral congenital cataracts.  Microcornea is common.  The eyebrows may be hypoplastic and the eyelashes likewise are sparse.  The lid fissures often slant down and telecanthus has been noted.  The distance between the two eyes appears reduced.  Blue sclerae, nystagmus, strabismus, and glaucoma are present in 10 to 30% of patients.

Systemic Features: 

The facies are sometimes described as 'bird-like' with a beaked nose, brachycephaly, and micrognathia.  Microstomia with a shortened ramus and forward displacement of the termporomandibular joints is characteristic. Upper airway obstruction may occur with severe respiratory distress.  The forehead is relatively prominent, the palate is highly arched, and the teeth are often small and some may be missing with misalignment of others.  A few teeth may even be present at birth (natal teeth).  Children appear petite and are often short in stature.  Scalp hair is thin, especially in the frontal and occipital areas, and the skin is atrophic.  Developmental delays are common but most patients have normal or near-normal intelligence.

Genetics

Most cases are sporadic but some have mutations in the GJA1 gene (6q21-q23.2).  Both autosomal dominant and autosomal recessive inheritance have been postulated.  Reproductive fitness may be low but rare affected individuals have had affected offspring.  Males and females are equally affected.

This disorder is allelic to oculodentodigital dysplasia (257850, 164200).

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

Airway obstruction may require intervention and its risks must be considered during administration of general anesthesia.  Lens opacification may be severe even early in life and requires prompt surgical intervention to prevent amblyopia.

References
Article Title: 
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