Shanklin, D. Radford; Mullins, Amanda C.; Baldwin, Heather S.
Ventilatory treatment of neonatal respiratory distress often results in bronchopulmonary dysplasia
from congenital surfactant deficiency due to mutants of transporter protein ABCA3. Association
of this condition with other severe disorders in premature newborns has not heretofore been
reported. A neonatal autopsy included an in vivo whole blood sample for genetic tcsting.
Autopsy revealed severe interstitial pulmonary fibrosis at age 8 days with heterozygotic mutation
p.E292V of ABCA3 and severe dystrophic retardation of cerebral cortcx and cerebellum.
Subsequently, 1300 archival neonatal autopsies, 1983-2006, were reviewed for comparable
concurrent findings and bronchopulmonary dysplasia or retarded cerebral dystrophy lacking the
other principal feature of this syndrome. Archival review revealed four similar cases and eight
less so, without gene analysis. Further review for bronchopulmonary dysplasia revealed 59 cases,
1983-2006. Several other examples of similar retarded migration of germinal matrix and
underdevelopment of cortical mantle, without pulmonary lesions of this type, were identified. The
determination of an ABCA3 mutation in one case of severe pulmonary fibrosis with significant
dystrophy of the brain and the identification of four highly similar archival cases and eight others
with partial pathological findings supports the designation of an independent disorder, here
referred to as the cerebroprrlmonary dysgenetic syndrome.