dental anomalies

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: 

Axenfeld-Rieger Syndrome, Type 1

Clinical Characteristics
Ocular Features: 

Axenfeld-Rieger syndrome consists of a heterogeneous group of disorders with overlapping features.  Common to all types are the presence of ocular, dental, facial, skeletal abnormalities and autosomal dominant inheritance.  Anterior chamber dysgenesis of some form is universally present and severe glaucoma occurs in 50% of patients.  This may have its onset in childhood with typical symptoms of congenital glaucoma such as photophobia, excessive tearing and corneal clouding.  Hypoplasia of the iris is common and when progressive may result in an ectopic pupil and/or pseudopolycoria.  Iris insertion and Schwalbe's line are often anteriorly displaced with iridocorneal adhesions, a pattern that leads to the inclusion of this disorder among those with iridogoniodysgenesis or anterior chamber dysgenesis.  Pupillary ectropion of the posterior pigmented layer of the iris may be seen.

There is considerable clinical overlap among conditions with iris dysgenesis.  Some patients with typical systemic features of Axenfeld-Rieger syndrome may even have typical anterior chamber features of Axenfeld-Rieger anomaly in one eye and severe iris hypoplasia resembling aniridia in the other.

Systemic Features: 

Dental anomalies and mid-facial hypoplasia secondary to underdeveloped maxillary sinuses are among the most common systemic features in type 1.  The nasal root often appears abnormally broad and the lower lip appears to protrude. The teeth are frequently small and conical in shape with wide spaces between them (diastema).  Some teeth may be missing.  The umbilicus may fail to involute normally and retains excessive, redundant skin that sometimes leads to the erroneous diagnosis of an umbilical hernia for which unnecessary surgery may be performed.  Hypospadius is frequently present while cardiac defects, sensorineural deafness, and anal stenosis are less common.

Genetics

There is clinical and genetic heterogeneity in this syndrome and precise classification of many families remains elusive without knowing the genotype.  Mutations in at least four genes are responsible and all are are responsible for phenotypes transmitted in autosomal dominant patterns.  Type 1 discussed here is caused by a mutation in the homeobox transcription factor gene, PITX2, located at 4q25-q26.  A type of iris hypoplasia (IH)/iridogoniodysgenesis (IGDS) (IRID2; 137600) disorder has been classified separately but is caused by a mutation in PITX2 as well and many cases have the same systemic features.  Mutations in the same gene have also been found in ring dermoid of the cornea (180550) and in some cases of Peters anomaly (604229).

RIEG2 (601499) is rare but a deletion of 13q14 has been reported in several cases.  Mapping in a large family with 11 affected individuals yielded a locus in the same region.  Clinical signs overlap types 1 and 3 with dental, craniofacial, and ocular features, but with hearing impairment and rare umbilical anomalies.

Mutations in the FOXC1 gene (6p25) may be responsible for RIEG3 (602482).  However, a family has been reported with a severe 'Axenfeld-Rieger phenotype' in which a digenic etiology may have been responsible: patients had mutations in both FOXC1 and PITX2. 

Heterozygous mutations in the PRDM5 gene (4q25-q26) have been identified in 4 members of a Pakistani family with typical features of the Axenfeld-Rieger syndrome. It is labeled type 4 Axenfeld-Rieger syndrome in this database. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

The presence of glaucoma requires prompt and vigorous treatment but control is difficult with blindness too often the result.  Oral surgery may be beneficial for dental problems.  Low vision aids can be useful.

References
Article Title: 

Axenfeld-Rieger syndrome

Seifi M, Walter MA. Axenfeld-Rieger syndrome. Clin Genet. 2017 Oct 3. doi: 10.1111/cge.13148. [Epub ahead of print] Review.

PubMed ID: 
28972279

The Rieger syndrome

Jorgenson RJ, Levin LS, Cross HE, Yoder F, Kelly TE. The Rieger syndrome. Am J Med Genet. 1978;2(3):307-18.

PubMed ID: 
263445

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