A09-24

31 WEEK EGA FEMALE WITH EPIDERMAL AGENESIS AND RECURRENT GI BLEEDING

Clinical Summary:

• 31-WEEK EGA 46,XX FEMALE, BORN AT AN OUTSIDE HOSPITAL

• C-SECTION 2o TO IUGR, PARTIAL PLACENTAL ABRUPTION, NUCHAL CORD X1, AND FETAL DECELERATIONS

• MAT HX: 16-YEAR-OLD G1P0 MOTHER, NON-CONTRIBUTORY HX

• PT TRANSFERRED FROM St FRANCIS TO UCIMC NICU 4/11/09

• CLIN COURSE:

• RECURRENT GI BLEEDING.

• ONGOING FLUID LOSSES

• DEAD ON 4/29/09

• COMPLETE UNRESTRICTED AUTOPSY PERFORMED AT 14:30 ON 4/30/09.

•

CLINICAL SUMMARY (2)

• CLINICAL DDX: • CONGENITAL PARTIAL CUTIS APLASIA• RESTRICTIVE DERMOPATHY• JUNCTIONAL TYPE VS. DYSTROPHIC

EPIDERMOLYSIS BULLOSA.

GROSS FINDINGS

• AGA FOR 34 WEEKS EGA:

• WEIGHT 1600 G, HT 38.6 CM, HEAD CIRC 29.8 CM, FL 6.3 CM

• 1. GENERALIZED MUSCLE, PERIPHERAL WASTING

• 2. LARGE ANTERIOR FONTANELLE, 6 CM IN GREATEST DIMENSION

• 3. PINCHED NOSE WITH PROMINENT NARES

• 4. HYPERTELORISM (INNER CANTHAL 2.4 CM, OUTER CANTHAL 6.1 CM),

• 10. Y-SHAPED, PARTIALLY FUSED 2ND/3RD TOES ON BOTH FEET

• 11. ROCKER BOTTOM FEET

• 12. JOINT CONTRACTURES, MOST PRONOUNCED AT RIGHT KNEE

GROSS FINDINGS- SKIN

• EXTENSIVE SOFT TISSUE DEHYDRATION, LOSS OF SUBCUTANEOUS FAT

• OPEN, GAPING MOUTH, NO EROSIONS ON ORAL MUCOSA

• LOW SET EARS WITH ADHESION OF UPPER HELICES TO SCALP

• TIGHTNESS OF SKIN ON EXTREMITIES• WITH RETRACTED, STRETCHED EYELIDS

GROSS FINDINGS:

FINDINGS (2)

•

Thymic depletion (10 g,exp. 19+/-4)

CARDIOVASCULAR SYSTEM

• CARDIOMEGALY; HEART WEIGHT 26.7G, EXPECTED 12.4+/-2.8 G

• MARKEDLY THICKENED LEFT (0.7 CM) AND SEPTAL (0.8 CM) MYOCARDIUM

• SMALL SECUNDUM TYPE ATRIAL SEPTAL DEFECT

• PATENT DUCTUS ARTERIOSUS

Inferior surface, heart and lungs

26.7g heart, biventricular hypertrophy

Atrial septal defect

Lungs, low power

Lungs, high power

GASTROINTESTINAL SYSTEM:

• HEPATOSPLENOMEGALY – LIVER; WEIGHT 127.1 G, EXPECTED 78.7 +/- 30.2 G– SPLEEN; WEIGHT 14.3 G, EXPECTED 6.4 +/- 3.0 G

• NECROTIZING ENTEROCOLITIS– 3 SITES OF NASCENT PERFORATION AND FECAL

MATERIAL PRESENT ON SEROSA, TRANSVERSE COLON.

Subendocardial LV- low power

NEC PERF SITE

Liver (327 g, exp 305 +/- 81)

Liver- centrilobular congestion

Bacterial seeding along portal vein

Thymus: Loss of CMJ’s

Cystic degeneration, Hassall’s corpuscles

Spleen: Red/White Pulp depletion

Splenic white pulp: leftover immature myeloids

PLACENTA• (PER ST. FRANCIS MEDICAL CENTER

ACCESSION NUMBER S09-2201):

• 1. TERM SINGLETON PLACENTA, NORMAL MEMBRANES, TRIVASCULAR CORD.

• 2. NO ADHERENT MOLDING BLOOD CLOT NOTED GROSSLY

Restrictive dermopathy (RD)• Rare, fatal, AD• Intrauterine fetal akinesia deformation sequence (FADS)

resulting in polyhydramnios, reduced fetal movements at ~31 weeks gestation

• FEATURES: – Dysmorphic facies, arthrogryposis, respiratory

insufficiency.

– Skin: NORMAL EPIDERMIS– Thin dermis with dense collagen fibers– Scant elastic fibers, and poorly developed skin

appendages.– Flattened rete ridges, straight DE junction

Genetics of RD

• 2/9 cases: Splice mutants of LMNA gene

• 7/9: early stop codon in ZMPSTE24– MMP involved in Lamin A processing,

prelamin accumulation

RD Features vs. Our

case

Restrictive DermopathyPinched nose Y 10 clinical subtypes

Taut, shiny skin Y Aplasia cutis congenita

small, round open mouth N

prominent cheeks YACC+ DEB = Bart Syndrome

skin fissures at flexures Y Pena Shokierulceration at pressure sites Y COFSShort, fingers, fixed in flexion Y Neu-LaxovaAnkylosis of all extremity joints Y Lethal Multiple Pterygium

Harlequin Ichthyosis

Normal blood chemistries ?Dystrophic Epidermolysis Bullosa

Negative VDRL, ANA, HIV YPoor mineralization of long bones ?Slender ribs ?Normal Echo ?Enlarged Fontanelle YNORMAL EPIDERMIS YDENSE DERMAL COLLAGEN, PARALLEL TO EPIDERMIS

mild fibrosis

DECREASED ADENXAL STRUCTURES ?NO DERMAL ELASTIN PresentFLAT DE JN, LOSS OF RETE RIDGES ?

Pulmonary hypoplasia NPremature teeth Nchoanal atresia Nadrenal hypoplasia NPDA YASD Yrocker bottom feet YZMPSTE24 stop codon NKaryotype abnormalities NMicroarray abnormalities NLMNA mutations N

DDX

• Harlequinn Ichthyosis

• Collodion baby

• Restrictive Dermopathy:

– AR, rigid/thick skin, arthrogryposis multiplex, pulmonary hypoplasia

– skeletal + facila anomalies

• 10 clinical subtypes

• Aplasia cutis congenita+ dystrophic epidermolysis bullosa (Bart syndrome)

• Pena Shokier

• COFS

• Neu-Laxova

• Lethal Multiple Pterygium

• Harlequin Ichthyosis

• Dystrophic Epidermolysis Bullosa