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Microphthalmia, Syndromic 9

OMIM ID:

autosomal recessive

Microphthalmia, Syndromic 9

Alternate Names

MCOPS9
Matthew-Wood syndrome
anophthalmia/microphthalmia and pulmonary hypoplasia
Spear syndrome
STRA6
microphthalmia and pulmonary agenesis

Defective Genes

STRA6

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

Inheritance

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

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

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.

Publications

Displaying 1 - 3 of 3

Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation

PubMedID: 17273977

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

Chitayat, David, et al. “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”. Am J Med Genet A, vol. 12, no. 143A, June 2007, pp. 1268-81, https://doi.org/10.1002/ajmg.a.31788.
PubMedID: 17506106

Two novel STRA6 mutations in a patient with anophthalmia and diaphragmatic eventration

PubMedID: 19213032