For Medical Professionals


Baylor Miraca Genetics Laboratories
FOXF1 – Related Disorders


Baylor College of Medicine
Clinical Trial – Genetic and Rare Diseases – Observational and Gene Discovery:
Molecular Genetics of Alveolar Capillary Dysplasia With Misalignment of Pulmonary Veins (ACDMPV) (H-8712)
*Currently Enrolling*

We demonstrated that haploinsufficiency of the transcriptional factor FOXF1 gene on 16q24.1 results in a lethal neonatal diffuse lung developmental disorder alveolar capillary dysplasia with misalignment of pulmonary veins. Infants affected with ACDMPV develop severe respiratory distress with pulmonary hypertension within the first two days of life and despite of intensive care die within first few days of life. We investigate the role of lncRNAs in a long range regulation of FOXF1 expression.

 

Postmortem genetic testing of the FOXF1 gene in the infant’s blood or lung autopsy or biopsy sample and parents’ blood samples will be performed on a research basis after the initial ACDMPV diagnosis is verified by an experienced pathologist at Texas Children’s Hospital in Houston. First it’s important to speak to your pathologist or physician so that your infant’s samples can be sent to Baylor College of Medicine. Your medical team should be able to coordinate this for you.

 

The samples and information required are:

 

1. A lung biopsy or autopsy sample of lung tissue. These can be sent as slides (stained or unstained) and/or formalin fixed paraffin embedded (FFPE) lung tissue block.

 

2. The local pathology report of the lung biopsy or autopsy, if available.

 

3. Your infant’s blood (if stored in +4C fridge) or isolated blood DNA (blood sample containing only genetic material) in EDTA tubes (purple top) if available. If a blood sample is not available frozen lung tissue can also be used to obtain DNA.

 

4. Completed and signed consent forms.

 

Contact Information:

 

Pawel Stankiewicz, M.D., Ph.D.
Associate Professor
Department of Molecular & Human Genetics
Baylor College of Medicine
One Baylor Plaza, Room ABBR-R809
Houston TX, 77030
Phone: (713) 798-5370
Fax: (713) 798-7418
Email: pawels@bcm.edu


In addition to the samples requested above, consider also providing other tissue (i.e. liver, stomach or intestine), to be preserved frozen along with paraffin embedded.

At a minimum, for babies with imminent death with one or more anomalies where ACDMPV is suspected, offer the option of DNA blood banking in the event that a possible genetic/inherited diagnosis is reached on autopsy and additional genetic testing may be warranted for genetic counseling purposes. A blood sample for genetic testing can be collected prior to or after an infant is placed on ECMO as the donor blood used for ECMO is depleted of the white blood cells that are used in genetic testing before it is given to the infant and therefore there is no chance of contamination.


Bilateral Lung Transplantation:

St. Louis Children’s Hospital in St. Louis, Missouri, United States, has the most active pediatric lung transplant program in the world. As of May 2013, a case study confirmed there are four patients with atypical presentations of ACDMPV currently living after each undergoing successful bilateral lung transplantation (BLT) (ages 4 months, 5 months, 9 months and 20 months of age at time of transplant). See Case Series Of Infants With Atypical Presentations Of Alveolar Capillary Dysplasia With Misalignment Of The Pulmonary Veins Who Underwent Bilateral Lung Transplantation. White, F., S. Sweet, R. M. Grady, A. Faro, P. Michelson, P. Eghtesady, U. Boston et al. (2013): In: Am J Respir Crit Care Med 187 (2013): A2251. In addition, in 2016, an ACDMPV patient in the UK and a second ACDMPV patient at Children’s Hospital of Philadelphia, Pennsylvania, USA each received a successful bilateral lung transplant at the ages of 5 months and 4 months, respectively.


Contacts:

1) Dr. Pawel Stankiewicz is the lead supervising researcher in ACDMPV at Baylor College of Medicine in Houston and the first contact for questions about ACDMPV genetic testing.

2) Dr. Przemyslaw Szafranski is a lead member of the ACDMPV research team at Baylor College of Medicine in Houston.

3) Dr. Csaba Galambos at Children’s Hospital Colorado and University of Colorado Denver.

4) Dr. Partha Sen at Northwestern University Feinberg School of Medicine.