Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect (PDAC) syndrome due to STRA6 mutations--what are the minimal criteria?
Microphthalmic syndrome 9 (OMIM601186) is a genetically and phenotypically variable condition, comprising anophthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac malformations (PDAC syndrome). Reported cases have all been associated with fetal/neonatal death or developmental delay. Recessive stimulated by retinoic acid gene 6 homolog (STRA6) mutations have recently been identified as the cause of cases of PDAC in which distinct, "bushy" eyebrows have been observed. We describe a patient with clinical anophthalmia, bushy eyebrows, patent ductus arteriosus, and normal development at age 30 months, who is a compound heterozygote for two novel STRA6 missense mutations. This patient's phenotype is consistent with the multisystemic malformations of PDAC syndrome, but is somewhat milder. This is the first living patient with compound heterozygous STRA6 mutations, which may explain her milder phenotype. We conclude that STRA6 analysis should be considered in all patients with clinical anophthalmia. Genetic counseling should be cautious with respect to long-term developmental outcomes.
Segel
Reeval
R
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. reevals@szmc.org.il
Levy-Lahad
Ephrat
E
Pasutto
Francesca
F
Picard
Elie
E
Rauch
Anita
A
Alterescu
Gheona
G
Schimmel
Michael S
MS
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D000853:Anophthalmos / Q000150:complications* / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000000981:diagnostic imaging; D002675:Child, Preschool; D020090:Chromosome Segregation; D004252:DNA Mutational Analysis; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics; D006548:Hernia, Diaphragmatic / Q000150:complications* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013902:Radiography, Thoracic; D013577:Syndrome; D014057:Tomography, X-Ray Computed
D008565:Membrane Proteins; C519685:STRA6 protein, human