Microphthalmia, Syndromic 9

Clinical Characteristics

Ocular Features:

Both microphthalmia and clinical anophthalmia have been described in this syndrome. However, autopsy has shown true anophthalmia in a few cases who were stillborn or died in the neonatal period. At least one eye can be cystic. The optic nerves are often hypoplastic and may be absent. High, upward-arching eyebrows may be seen.

Systemic Features:

An early manifestation of this disorder is neonatal pulmonary distress. The lungs are usually hypoplastic or malformed. Cardiac malformations such as patent ductus arteriosus, septal and valvular defects, tetralogy of Fallot, and single ventricles are often present. Diaphragmatic hernias or defects are common but hiatal hernias and frank eventration of abdominal contents have also been reported. Renal anomalies and intrauterine growth retardation have been noted.

Some infants have micrognathia, low-set ears, a broad nasal bridge, brachycephaly, and midline clefts of the palate. Cerebral malformations are seldom present.

Genetics

Homozygous mutations in the STRA6 [1] gene (15q24.1) have been found in a few cases which suggests autosomal recessive inheritance. Parental consanguinity has been reported in some families.

Treatment

Treatment Options:

Treatment is directed at the repair of the organ defects in selected cases that have survival potential. Survival rates are poor but those less severely affected may live for a decade.

References

Article Title:

Two novel STRA6 mutations in a patient with anophthalmia and diaphragmatic eventration (Letter) [2]

West B, Bove KE, Slavotinek AM. Two novel STRA6 mutations in a patient with anophthalmia and diaphragmatic eventration (Letter). Am J Med Genet A. 2009 Mar;149A(3):539-42.

PubMed ID:

19213032

The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal [3]

Chitayat D, Sroka H, Keating S, Colby RS, Ryan G, Toi A, Blaser S, Viero S, Devisme L, Boute-B?(c)n?(c)jean O, Manouvrier-Hanu S, Mortier G, Loeys B, Rauch A, Bitoun P. The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal recessive inheritance. Am J Med Genet A. 2007 Jun 15;143A(12):1268-81.

PubMed ID:

17506106

Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation [4]

Pasutto F, Sticht H, Hammersen G, Gillessen-Kaesbach G, Fitzpatrick DR, N?ornberg G, Brasch F, Schirmer-Zimmermann H, Tolmie JL, Chitayat D, Houge G, Fern?degndez-Mart??nez L, Keating S, Mortier G, Hennekam RC, von der Wense A, Slavotinek A, Meinecke P, Bitoun P, Becker C, N?ornberg P, Reis A, Rauch A. Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am J Hum Genet. 2007 Mar;80(3):550-60.

PubMed ID:

17273977