United States Court of Appeals

for the Federal Circuit

______________________ 

HEIDI SHARPE, AS THE LEGAL

REPRESENTATIVE OF HER MINOR CHILD, L.M.,

Petitioner-Appellant

v.

SECRETARY OF HEALTH AND HUMAN 

SERVICES,

Respondent-Appellee

______________________ 

2019-1951

______________________ 

Appeal from the United States Court of Federal Claims 

in No. 1:14-vv-00065-NBF, Senior Judge Nancy B. Firestone. 

______________________ 

Decided: July 1, 2020

______________________ 

CURTIS RANDAL WEBB, Twin Falls, ID, argued for petitioner-appellant.

VORIS EDWARD JOHNSON, JR., Vaccine/Torts Branch, 

Civil Division, United States Department of Justice, Washington, DC, argued for respondent-appellee. Also 

represented by JOSEPH H. HUNT, C. SALVATORE D'ALESSIO,

HEATHER LYNN PEARLMAN, CATHARINE E. REEVES. 

______________________ 

Case: 19-1951 Document: 42 Page: 1 Filed: 07/01/2020
2 SHARPE v. HHS

Before MOORE, REYNA, and TARANTO, Circuit Judges.

REYNA, Circuit Judge. 

Heidi Sharpe, on behalf of her minor daughter, L.M., 

appeals from a judgment of the United States Court of Federal Claims upholding the Special Master’s dismissal of 

L.M.’s petition for compensation under the National Childhood Vaccine Injury Act of 1986. For the reasons set forth 

below, we affirm the Special Master’s denial of Petitioner’s 

on-table claim and vacate and remand the Special Master’s 

denial of Petitioner’s off-table claim for further proceedings. 

BACKGROUND

I 

On July 26, 2010, L.M. was born at full-term and developed normally for the first six months of her life. By six 

months, L.M. could roll over, push herself up, play, giggle, 

interact with others, and maintain good head control. 

L.M.’s father testified that L.M. “loved to play in [his] lap, 

grab her daddy’s hat and nose, shirt, anything she could 

get her hands on.” J.A. 173. On the afternoon of February 

10, 2011, at her six-month check-up, L.M. received several 

childhood vaccines, including the diphtheria-tetanus-acellular pertussis (“DTaP”) vaccination. By 7:00 pm that 

evening, L.M. had a fever, was lethargic, had poor muscle 

tone, and would not eat. Concerned, L.M.’s mother, Heidi 

Sharpe (“Petitioner”), called the local hospital’s emergency 

room department twice in the early morning hours of February 11, 2011, and then called her daughter’s pediatrician 

later that morning. Petitioner was instructed to administer ibuprofen and Tylenol to L.M. and to bring L.M. in for 

a doctor’s visit on February 14, 2011, if L.M. did not appear 

to improve. 

Petitioner testified that from February 11 to February 

14, 2011, L.M. continued to have a fever, remained lethargic, had poor head control, did not interact with her 

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SHARPE v. HHS 3

surroundings, and could not focus on her mother while 

feeding. Petitioner also testified that any disturbance 

caused L.M. to scream. 

On the morning of February 15, 2011, L.M. experienced 

a seizure. Petitioner rushed L.M. to the emergency room 

department at a local hospital. The medical records reveal 

that upon arrival, L.M. was “fairly floppy in her motor 

skills,” that she could not sit by herself, and that she had 

“fairly poor head control.” J.A. 144. The medical records 

also note that one month prior, Petitioner had observed 

L.M. having a few episodes of “spacing out,” where L.M. 

had a “strange look in her eye and was not responsive for 

several seconds.” J.A. 143. 

L.M. had a second and third seizure on February 15, 

2011, and was then transferred to a second hospital—St. 

Vincent’s. The St. Vincent’s medical records show that 

L.M. had poor head control and diminished responsiveness. 

On February 16, 2011, L.M. was diagnosed with infantile spasms. L.M. was discharged the following day. L.M.’s 

medical records indicate that, on February 21, 2011, she

continued to have poor head control, and by March 21, 

2011, L.M. was experiencing about five to six seizures a 

day. By April 11, 2011, L.M.’s doctors reported that L.M.’s 

eyes “don’t really seem to focus on anything,” that L.M. did 

not have an “interactive smile,” and that L.M. “didn’t have 

good head control at all.” J.A. 130.

Since April 2011, L.M. continues to experience seizures 

and has experienced profound physical and cognitive developmental delays. At the time of the Special Master’s compensation hearing in this case, L.M. was about 7 years and 

5 months of age. At this age, L.M. could crawl and walk 

with the assistance of a walker. She had a poorly coordinated grasp, suffered cortical visual impairments, and was 

nonverbal, though she could use a few signs to express 

ideas such as “hungry,” “thirsty,” “I want,” “yes,” and “no.” 

See J.A. 8, J.A. 346–51. 

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4 SHARPE v. HHS

Over the years, L.M. has seen various doctors and has 

undergone various therapies and testing. Key here, genetic 

testing revealed that L.M. was born with a genetic mutation in the stem region of the dynein cytoplasmic 1 heavy 

chain 1 gene (“DYNC1H1 gene”). 

II

On January 27, 2014, Petitioner filed a petition for 

compensation under the National Vaccine Injury Compensation Program on behalf of L.M. Petitioner alleged that 

the vaccinations administered to L.M. on February 10, 

2011, significantly aggravated L.M.’s pre-existing condition under two alternative theories. According to Petitioner’s first theory, L.M. had a pre-existing 

“encephalopathy” as defined in the Vaccine Act and that 

the DTaP vaccination significantly aggravated L.M.’s encephalopathy within 72 hours of administration, resulting 

in a compensable “on-table” injury. According to Petitioner’s second theory, L.M. had a pre-existing “seizure disorder” and the February 10th vaccinations, as opposed to 

just the DTaP vaccination, significantly aggravated L.M.’s 

seizure disorder, resulting in a compensable “off-table” injury. 

The Special Master denied the petition for compensation. The Special Master found that Petitioner’s on-table 

significant aggravation claim failed “because it relied on a 

legally untenable construction” of the Vaccine Act’s definition of “encephalopathy.” J.A. 3. The Special Master also 

found that Petitioner’s off-table significant aggravation 

claim failed because “Petitioner did not successfully establish that the vaccines did so (or that they could specifically 

worsen the expected course of an individual with the precise mutation possessed by L.M.).” Id. (emphasis in original). Specifically, the Special Master denied Petitioner’s 

off-table significant aggravation claim because L.M.’s genetic mutation was “the most compelling explanation for 

her predisposition to develop a seizure disorder.” J.A. 56. 

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SHARPE v. HHS 5

The United States Court of Federal Claims affirmed 

the Special Master’s denial of both claims. Petitioner 

timely appeals. We have jurisdiction under 42 U.S.C. 

§ 300aa–12(f).

DISCUSSION

This court reviews de novo a ruling by the Court of Federal Claims on a special master’s decision to grant or deny 

entitlement to compensation under the Vaccine Act. See 

Lampe v. Sec’y of Health & Human Servs., 219 F.3d 1357, 

1360 (Fed. Cir. 2000). This court thus performs the same 

task as the Court of Federal Claims and reviews the special 

master’s legal determinations de novo, fact findings under 

an arbitrary and capricious standard, and discretionary 

rulings for an abuse of discretion. See Munn v. Sec’y of the 

Dep’t of Health & Human Servs., 970 F.2d 863, 870–73, 870 

n.10 (Fed. Cir. 1992). 

Before turning to Petitioner’s claims, we review two aspects of the Vaccine Injury Program. First, a petitioner can 

allege that the vaccine caused the onset of her injuries (an 

onset claim) or that the vaccine significantly aggravated 

her pre-existing condition (a significant aggravation 

claim). See 42 U.S.C. § 300aa–11(c)(1)(C); see also Whitecotton ex rel. Whitecotton v. Sec’y of Health & Human 

Servs., 81 F.3d 1099, 1102–03 (Fed. Cir. 1996). 

Second, the Vaccine Act includes a “Vaccine Injury Table” (“Vaccine Table” or “Table”), which lists various injuries associated with various vaccines, and provides a time 

period with respect to each injury associated with each vaccine. 42 U.S.C. § 300aa–14(a). Included with the statutory 

table is a list of definitions for various Table injuries, 

known as the Qualifications and Aids to Interpretation 

(“QAI”). See id., § 300aa–14(b). The Vaccine Act provides 

that the Secretary of the Department of Health and Human Services (“HHS”) may modify the Vaccine Table, as 

well as the QAIs, through duly promulgated regulations. 

Id., § 300aa–14(c); see also Terran ex rel. Terran v. Sec’y of 

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6 SHARPE v. HHS

Health & Human Servs., 195 F.3d 1302, 1308 (Fed. Cir. 

1999). The Secretary of HHS has promulgated a revised 

Vaccine Table and QAI. See 42 C.F.R. § 100.3. 

If a petitioner can show that she experienced the first 

“symptom or manifestation” of a Table injury or a significant aggravation of a Table injury within the prescribed 

time period in the Vaccine Table, causation is presumed, 

and the petitioner has made her prima facie case of entitlement to compensation. See 42 U.S.C. §§ 300aa–

11(c)(1)(C)(i), 300aa–13(a)(1)(A). These claims are known 

as “on-table” claims. 

If a petitioner cannot show that she experienced a Table injury or that such injury occurred within the prescribed time frame in the Vaccine Table, a petitioner will 

not be afforded a presumption of causation. Instead, the 

petitioner must prove that the vaccine in fact caused her 

injuries by a preponderance of the evidence. 42 U.S.C. 

§§ 300aa–11(c)(1)(C)(ii), 300aa–13(a)(1)(A). These claims 

are known as “off-table” claims. See Whitecotton, 81 F.3d 

at 1102. Notably, the preponderance of the evidence standard for off-table claims does not require a petitioner to

prove causation with scientific certainty. See Knudsen ex 

rel. Knudsen v. Sec’y of Dep’t of Health & Human Servs., 35 

F.3d 543, 548–49 (Fed. Cir. 1994). Rather, “[c]ausation in 

fact under the Vaccine Act is . . . based on the circumstances of the particular case . . . [and] involves ascertaining whether a sequence of cause and effect is ‘logical’ and 

legally probable.” Id. With this backdrop, we now turn to 

Petitioner’s on-table claim, followed by Petitioner’s off-table claim. 

I. On-Table Claim 

Petitioner argues that the Special Master legally erred 

in denying her on-table significant aggravation claim, 

which alleges that the DTaP vaccination L.M. received on 

February 10, 2011, significantly aggravated her TableCase: 19-1951 Document: 42 Page: 6 Filed: 07/01/2020
SHARPE v. HHS 7

injury of “encephalopathy” within 72 hours. For the below 

reasons, we disagree with Petitioner. 

For her on-table significant aggravation claim, Petitioner had to demonstrate that: (a) pre-vaccination, L.M. 

experienced an “encephalopathy,” as defined in the QAI 

promulgated by HHS; (b) L.M. suffered a significant aggravation of that encephalopathy post-vaccination; and (c) the 

first symptom or manifestation of the significant aggravation of L.M.’s encephalopathy occurred within 72 hours 

post-vaccination. See Whitecotton, 81 F.3d at 1107. At issue here is whether L.M. experienced a QAI-defined “encephalopathy” pre-vaccination. 

Pursuant to the QAI issued by HHS, an individual suffers an “encephalopathy” only if “such recipient manifests, 

within the applicable period,” an “acute encephalopathy” 

followed by “a chronic encephalopathy [which] persists in 

such person for more than 6 months beyond the date of vaccination.” 42 C.F.R. § 100.3(b)(2)(2014). For children less 

than 18 months of age, “[a]n acute encephalopathy is indicated by a significantly decreased level of consciousness 

lasting for at least 24 hours.” Id., § 100.3(b)(2)(i)(A).

In DeRoche v. Secretary of the Department of Health & 

Human Services, the special master recognized that under 

the QAI’s definition of an encephalopathy—an acute encephalopathy followed by a chronic encephalopathy for six 

months—petitioners face the “infeasible” task of showing a 

significant aggravation of such a serious, chronic injury. 

No. 97-643V, 2002 WL 603087, *27 (Fed. Cl. Spec. Mstr. 

Mar. 28, 2002). The special master also explained that 

given the short timetable for childhood vaccines, a child petitioner would have received an immunization before six 

months had elapsed, rendering it difficult to establish an 

aggravation of an encephalopathy. Id. Thus, the special 

master construed the QAI’s definition of encephalopathy to 

require only an acute encephalopathy when applied to ontable, significant aggravation claims. Id. at *29. 

Case: 19-1951 Document: 42 Page: 7 Filed: 07/01/2020
8 SHARPE v. HHS

In this case, the Special Master followed the DeRoche

approach. Specifically, the Special Master narrowed the 

QAI’s definition of encephalopathy to an acute encephalopathy only. Here, there is no real dispute that pre-vaccination, L.M. did not experience an acute encephalopathy. At 

most, L.M. experienced a few episodes of “spacing out” one 

month prior to her February 10, 2011 vaccinations, which 

fall short of a decreased level of consciousness for a 24-hour 

period. Accordingly, the Special Master found that L.M. 

did not experience an acute encephalopathy and denied 

L.M.’s on-table significant aggravation claim. 

We see no error in the Special Master’s determination. 

“All statutes must be construed in the light of their purpose. A literal reading of them which would lead to absurd 

results is to be avoided when they can be given a reasonable application consistent with their words and with the 

legislative purpose.” Haggar Co. v. Helvering, 308 U.S. 

389, 394 (1940). This principle of statutory interpretation 

applies to the interpretation of regulations. See Trustees of 

Indiana Univ. v. United States, 618 F.2d 736, 739 (Ct. Cl. 

1980). Here, the QAI definition of encephalopathy, i.e., an 

acute encephalopathy followed by a chronic encephalopathy, would lead to an absurd result if literally applied to 

on-table significant aggravation claims. Rather, the dual 

requirement for acute and chronic encephalopathies is better suited for on-table onset claims. Thus, as in DeRoche, 

it was reasonable for the Special Master to construe “encephalopathy” to mean only an acute encephalopathy for 

Petitioner’s on-table significant aggravation claim. Additionally, the record is clear that L.M. did not experience an 

acute encephalopathy pre-vaccination. 

Petitioner argues, however, that the Special Master did 

not go far enough in correcting the QAI’s definition of encephalopathy for on-table significant aggravation claims. 

Appellant’s Br. at 26. Specifically, Petitioner argues that 

even the more limited definition of encephalopathy articulated in DeRoche, i.e., an acute encephalopathy, should not 

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SHARPE v. HHS 9

apply here. Id. at 23. This is because, according to Petitioner, most encephalopathies are not acute until after vaccination, and, thus, it would be nearly impossible to prove 

a significant aggravation of a pre-existing acute encephalopathy. Id. at 28. Rather, Petitioner argues, the Special 

Master should have applied the “common, ordinary, and accepted meaning” of an encephalopathy, which is “a disease 

of the brain.” Id. at 23, 25. 

Petitioner, however, provides no support that most encephalopathies do not become acute until after vaccination. 

In the absence of such evidence, Petitioner’s conclusory argument is not a sufficient ground for excising the acute requirement from the QAI’s definition of encephalopathy. 

For the above reasons, we affirm the Special Master’s 

denial of Petitioner’s on-table claim. 

II. Off-Table Claim 

Petitioner also challenges the Special Master’s denial 

of her off-table claim. According to Petitioner, L.M.’s receipt of vaccinations on February 10, 2011, significantly aggravated L.M.’s pre-existing “seizure disorder.” J.A. 18, 

J.A. 55. To prevail on an off-table significant aggravation 

claim, a petitioner must satisfy the six-prong inquiry announced in Loving ex rel. Loving v. Secretary of Health & 

Human Services, 86 Fed. Cl. 135 (2009). Under the Loving 

framework, a petitioner must establish: 

(1) the person’s condition prior to administration of 

the vaccine, (2) the person’s current condition (or 

the condition following the vaccination if that is 

also pertinent), (3) whether the person’s current 

condition constitutes a “significant aggravation” of 

the person’s condition prior to vaccination, (4) a 

medical theory causally connecting such a significantly worsened condition to the vaccination, (5) a 

logical sequence of cause and effect showing that

the vaccination was the reason for the significant 

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10 SHARPE v. HHS

aggravation, and (6) a showing of a proximate temporal relationship between the vaccination and the 

significant aggravation.

Id. at 144; see also W.C. v. Sec’y of Health & Human Servs., 

704 F.3d 1352, 1357 (Fed. Cir. 2013) (holding that “the Loving case provides the correct framework for evaluating offtable significant aggravation claims”).

If a petitioner successfully satisfies the Loving inquiry, 

the burden shifts to the government to prove by a preponderance of the evidence that a “factor unrelated” to the vaccine caused the petitioner’s injuries. 42 U.S.C. § 300aa–

13(a)(1)(A)–(B); see also Hines v. Sec’y of the Dep’t of Health 

& Human Servs., 940 F.2d 1518, 1525 (Fed. Cir. 1991). If 

the government fails to carry its burden, the petitioner is 

entitled to compensation. 

Here, the Special Master determined that Petitioner 

satisfied Loving prongs 1, 2, and 6. The Special Master, 

however, determined that Petitioner failed to satisfy Loving prongs 3, 4, and 5 and, thus, did not make out her prima 

facie case of causation-in-fact. The Special Master also determined that even if Petitioner had proven causation-infact, she still was not entitled to compensation because the 

government sufficiently satisfied the “factor unrelated” inquiry. Specifically, the Special Master determined that 

L.M.’s DYNC1H1 gene mutation, and not the vaccination, 

was the sole, substantial cause of L.M.’s significantly aggravated seizure disorder. On appeal, Petitioner challenges the Special Master’s determinations under Loving 

prongs 3, 4, and 5, and the “factor unrelated” inquiry. We 

discuss each of these factors below. 

A. Loving prong 3 

Petitioner argues that the Special Master legally erred 

in applying Loving prong 3. We agree with Petitioner. The 

Special Master’s Loving prong 3 analysis makes clear he 

required Petitioner to prove the expected outcome for a 

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SHARPE v. HHS 11

child with a DYNC1H1 gene mutation and to show that 

L.M.’s current, post-vaccination condition was worse than 

that expected outcome. Specifically, the Special Master explained that “[s]ubsumed within the Loving analysis is the 

requirement to evaluate the likely natural course of an injured party’s preexisting disease, in order to determine 

whether the vaccine made the petitioner worse than he 

would have been but for the vaccination.” J.A. 36; see also 

J.A. 51 (noting that Loving prong 3 required “an evaluation 

of what is known about the preexisting mutation and its 

likely impact on an affected individual’s life” (emphasis 

added)). Loving prong 3, however, does not require a petitioner to demonstrate an expected outcome and that her 

current-post vaccination condition was worse than such expected outcome. To understand why this is not required, 

we believe it necessary to review this court’s development 

of the significant aggravation claim framework. 

The Court of Federal Claims announced the first 

framework for analyzing on-table significant aggravation 

claims in Misasi v. Secretary of the Department of Health & 

Human Services, 23 Cl. Ct. 322 (1991). The Misasi inquiry 

required a special master to compare “the actual condition 

of the child after the vaccination with the child’s predicted 

condition had the vaccine not been administered.” Whitecotton, 81 F.3d at 1105 (discussing the Misasi framework). 

“If the child’s current condition represent[ed] a significant 

aggravation of the child’s expected condition, then the child 

[was] entitled to the presumption” of causation for on-table 

claims. Id. The reasoning underlying the Misasi inquiry

was to “distinguish cases in which the vaccination caused 

the significant aggravation from cases in which the vaccination had no detrimental effect.” Id. 

In Whitecotton, in discussing an on-table significant aggravation claim, we squarely rejected the Misasi inquiry as 

“improperly requir[ing] a petitioner to prove, as part of her 

prima facie case, that petitioner’s significant aggravation 

was not caused by a pre-existing injury.” Id. at 1106

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12 SHARPE v. HHS

(emphasis in original). We instead explained that the Vaccine Act only requires a “comparison of the person’s prevaccination condition with the person’s current, post-vaccination condition.” Id. at 1107 (citing 42 U.S.C. § 300aa–

33(4)). This comparison is now known as prong 3 of the 

Whitecotton inquiry for on-table significant aggravation 

claims. Id.1 

The Court of Federal Claims then announced the Loving inquiry for off-table significant aggravation claims. We 

subsequently approved the Loving approach for such 

claims, W.C., 704 F.3d at 1357, and the government accepts 

that approach. Key here, the Loving court incorporated 

prongs 1, 2, and 3 of the Whitecotton inquiry into its analysis. Loving, 86 Fed. Cl. at 144. The last three prongs of 

the Loving inquiry correspond to the three-part inquiry articulated in Althen v. Secretary of Health & Human Services, 418 F.3d 1274 (Fed. Cir. 2005). Id. 

Thus, Loving prong 3, like Whitecotton prong 3, only 

requires a comparison of a petitioner’s current, post1 The Whitecotton inquiry for on-table significant aggravation claims requires a court to:

(1) assess the person’s condition prior to administration of the vaccine, 

(2) assess the person’s current condition, . . . 

(3) determine if the person’s current condition 

constitutes a “significant aggravation” of the 

person’s condition prior to vaccination within 

the meaning of the statute . . . . and[]

(4) determine whether the first symptom or manifestation of the significant aggravation occurred within the time period prescribed by 

the Table. 

Whitecotton, 81 F.3d at 1107. 

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SHARPE v. HHS 13

vaccination condition with her pre-vaccination condition. 

To require a petitioner to prove her expected outcome and 

that her post-vaccination condition is worse than this expected outcome, as the Special Master required here, revives the defunct Misasi test and is improper under our 

precedent. 

The impropriety of the Misasi test is readily apparent 

in gene mutation cases, in which a clinical outcome is

nearly impossible to predict. As the government’s own expert, Dr. Descartes, testified: 

The dream of the geneticist is to find genotype-phenotype correlation, because when a parent comes to 

talk to me, the first thing they want to know, is my

child going to be able to do this and that? How long 

my child is going to live? Do you have any answer 

to these questions? The mutation that you found, 

what do you know? And the answer, unfortunately, 

to all these questions that parents ask all the time 

is we don’t know. 

J.A. 389: 5–12 (emphasis added). 

The Special Master reasoned that a comparison of 

L.M.’s current, post-vaccination condition with the expected course of a DYNC1H1 gene mutation is consistent 

with Stone ex rel. Stone v. Secretary of Health & Human 

Services, 676 F.3d 1373 (Fed. Cir. 2012). The Special Master misread Stone. In Stone, we explained that “evidence 

of other possible sources of injury can be relevant not only 

to the ‘factors unrelated’ [inquiry], but also to whether a 

prima facie showing has been made that the vaccine was a 

substantial factor in causing the injury in question.” 676 

F.3d at 1379. We also explained that “no evidence should 

be embargoed from the special master’s consideration 

simply because it is also relevant to another inquiry under 

the statute.” Id. at 1380. We agree with Stone that a court 

should consider all evidence in the record, including evidence of other possible sources of injury. There is, however, 

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14 SHARPE v. HHS

a fine line between a court properly considering evidence 

in the record, Stone, 676 F.3d at 1380, and improperly placing the burden on the petitioner to prove that her significantly aggravated condition was not caused by her gene 

mutation. See Whitecotton, 81 F.3d at 1106. Here, the Special Master unequivocally engaged in the latter. See J.A. 

36, 51. 

The government argues that the Special Master’s application of Loving prong 3 was in line with our decision in 

Locane v. Secretary of Health & Human Services, 685 F.3d 

1375 (Fed. Cir. 2012). We disagree. In Locane, the special 

master did not require the petitioner to prove that her significantly aggravated condition was not caused by her preexisting condition. 685 F.3d at 1381. Instead, the special 

master found that the petitioner’s condition “was not affected by the vaccination.” Id. at 1378. This proposition is 

not new. In any vaccine case, if the evidence as a whole 

ultimately shows that the vaccine was not a substantial 

factor in causing the petitioner’s injury, then compensation 

should be denied.2 

For the above reasons, the Special Master legally erred 

in applying Loving prong 3. 

2 To the extent that Locane could be read as requiring a comparison of a petitioner’s current, post-vaccination 

condition with her expected outcome to establish a significant aggravation, then that portion of Locane conflicts with 

Whitecotton. Because Whitecotton pre-dates Locane, 

Whitecotton would govern. See Newell Cos. v. Kenney Mfg. 

Co., 864 F.2d 757, 765 (Fed. Cir. 1988) (“Where there is direct conflict, the precedential decision is the first.”).

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SHARPE v. HHS 15

B. Loving prong 4 

Petitioner argues that the Special Master legally erred 

in applying Loving prong 4. For the below reasons, we 

agree with Petitioner.

The Special Master’s Loving prong 4 analysis indicates 

that Petitioner had to eliminate L.M.’s pre-existing gene 

mutation as the cause of her significantly aggravated seizure disorder. Specifically, the Special Master faulted Petitioner for not sufficiently showing that L.M.’s gene 

mutation would have “more likely than not” resulted in a 

benign trajectory. J.A. 54. The Special Master also noted 

that: 

No doubt future research may . . . make it easier to 

conclude that a tail-located DYNC mutation is unlikely to be pathogenic [i.e., disease-causing] in the 

manner relevant herein. But such research does 

not yet exist, and on the present record I do not find 

that Petitioner’s showing established the first “can 

cause” [Loving] prong.

Id. (emphasis added). This analysis is legally flawed.

First, a petitioner may be able to make out a prima facie case under Loving prong 4 without eliminating a preexisting condition as the cause of her significantly aggravated injury. And if the petitioner does so, the burden falls 

on the government under the “factor unrelated” inquiry to 

show that the pre-existing condition caused the significantly worsened condition. Walther v. Sec’y of Health & 

Human Servs., 485 F.3d 1146, 1151 (Fed. Cir. 2007) (noting 

that “the government bears the burden of establishing alternative causation . . . once the petitioner has established 

a prima facie case”). Under Loving prong 4, a petitioner 

need only provide a “medical theory causally connecting 

[petitioner’s] significantly worsened condition to the vaccination.” Loving, 86 Fed. Cl. at 144. In other words, Petitioner was required to present a medically plausible theory 

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16 SHARPE v. HHS

demonstrating that a vaccine “can” cause a significant 

worsening of L.M.’s seizure disorder. See Pafford ex rel. 

Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 

1356–57 (Fed. Cir. 2006).

Second, the Special Master should not have been concerned with what “future research” may show but rather 

with the research presented in the record. See Knudsen, 

35 F.3d at 549.

[A court] is . . . not to be seen as a vehicle for ascertaining precisely how and why DTP and other vaccines sometimes destroy the health and lives of 

certain children while safely immunizing most others. This research is for scientists, engineers, and 

doctors working in hospitals, laboratories, medical 

institutes, pharmaceutical companies, and government agencies. The special masters are not “diagnosing” vaccine-related injuries. The sole issues for 

the special master are, based on the record evidence as a whole and the totality of the case, 

whether it has been shown by a preponderance of 

the evidence that a vaccine caused the child’s injury. 

Id. The Vaccine Injury Program, after all, is designed to 

“allow the finding of causation in a field bereft of complete 

and direct proof of how vaccines affect the human body.”

Althen, 418 F.3d at 1280.

The Special Master separately determined that Petitioner failed under Loving prong 4 because the medical literature regarding the SCN1A gene mutation, a different 

gene mutation than at issue here, “effectively rebutted” Petitioner’s medical theory. J.A. 55. The Special Master emphasized that because “the environmental impact of 

vaccination was not deemed significant enough to alter the 

course” of a SCN1A gene mutation, the same must be true 

for the DYNC1H1 gene mutation. Id. (emphasis removed). 

The Special Master noted that Petitioner “perhaps could 

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SHARPE v. HHS 17

have” succeeded under Loving prong 4 if Petitioner had “rebutted evidence offered about SCN1A mutations.” Id., 

n.50. 

The Special Master doubles down on his legal error. 

Petitioner only had to set forth a medical theory that L.M.’s 

February 10th vaccinations could worsen her seizure disorder. Loving, 86 Fed. Cl. at 144. Yet, the Special Master 

required Petitioner either to prove an additional medical 

theory—that vaccines could alter the course of an SCN1A 

mutation—or to disprove the applicability of SCN1A research to DYNC1H1 patients. This was not Petitioner’s 

burden to carry. 

The Special Master then determined that Petitioner 

separately failed to meet Loving prong 4 because the patient cited in the Ambry report (“Ambry patient”), a report 

cited by both parties’ experts, effectively disproved Petitioner’s medical theory. See J.A. 54. According to the Special Master, the Ambry patient belied Petitioner’s medical 

theory because the Ambry patient had the same genetic 

mutation and same severe outcome as L.M. See J.A. 52–

54. This conclusion is arbitrary and capricious and must 

be set aside. See Paluck v. Sec’y of Health & Human Servs., 

786 F.3d 1373, 1380 (Fed. Cir. 2015) (noting that this court 

has “a duty to ensure that the special master has properly 

applied [the] Vaccine Act . . . and articulated a rational basis for [his] decision” (internal quotation marks omitted)). 

Neither party established whether the Ambry patient faced 

any of the same environmental factors that arguably affected the outcome of L.M.’s mutation, including vaccination. If the Ambry patient was also vaccinated, then the 

patient’s condition could also have been caused by her vaccine.3 Additionally, even if the Ambry patient suffered 

3 The Special Master recognized that the Ambry patient may or may not have received any vaccines but found 

this point “only strengthens the relevance” of the Ambry 

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18 SHARPE v. HHS

from the same condition as L.M. without vaccination, a single example cannot establish the typical progression of a 

disease; nor is such a singular example sufficient to disprove a medical theory that a vaccine can cause aggravation in some patients. Yet, it is clear from the record that 

the Special Master concluded that given the Ambry patient, L.M. was destined to have a severe outcome. See 

J.A. 25, 54. This deterministic mindset does not belong in 

the Vaccine Injury Program.4 

Lastly, the Special Master found that Petitioner’s medical theory—that vaccines could constitute a sufficient “environmental insult” to exacerbate the effects of L.M.’s 

underlying seizure disorder—was not persuasive. See 

J.A. 55; see also J.A. 21. Specifically, the Special Master 

explained that Petitioner’s medical expert did not “offer literature specifically addressing the propensity of any vaccine to exacerbate a disease otherwise attributable to a 

patient. J.A. 54 n.49. For if the Ambry patient experienced 

the same outcome as L.M. without being vaccinated, the 

Special Master noted, “the conclusion that the vaccines had 

no impact on L.M.’s outcome is strengthened.” Id. We reject this finding because it is based on an unsubstantiated 

fact—that the Ambry patient was not vaccinated. 

4 As the government’s expert testified, geneticists 

“dream” of discovering a “genotype-phenotype correlation” 

which would allow geneticists to predict the outcome of a 

child with a gene mutation, but geneticists are not there 

yet. See J.A. 389: 5–12. Thus, until science provides us 

with better answers, it is not the place of a court to assume 

that a child with a genetic mutation is destined to have a 

severe outcome. “The role of genetic knowledge in the vaccine compensation program requires deeper understanding 

than [a] ‘destiny’ pejorative . . . .” Oliver v. Sec’y of Health 

& Human Servs., 911 F.3d 1381, 1384 (Fed. Cir. 2009) 

(Newman, J., dissenting in denial of rehearing en banc). 

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SHARPE v. HHS 19

genetic mutation and this component of his overall opinion 

had a conclusory character to it.” J.A. 21. The Special Master’s finding is legally and factually erroneous. 

First, medical literature is not required under Loving 

prong 4. See Andreu ex rel. Andreu v. Sec’y of Health & 

Human Servs., 569 F.3d 1367, 1378–79 (Fed. Cir. 2009) (explaining that a petitioner can satisfy her burden to prove a 

plausible medical theory without resort to medical literature, epidemiological studies, demonstration of a specific 

mechanism, or a generally accepted medical theory). “Requiring epidemiologic studies . . . or general acceptance in 

the scientific or medical communities . . . impermissibly 

raises a claimant’s burden under the Vaccine Act and hinders the system created by Congress, in which close calls 

regarding causation are resolved in favor of injured claimants.” Id. at 1378 (internal quotation marks omitted). 

Thus, the Special Master’s rejection of Petitioner’s medical 

theory due to an absence of medical literature was legal error. 

Second, contrary to the Special Master’s determination, the record shows that Petitioner’s medical theory was 

not merely based on “personal supposition.” J.A. 55. Rather, Petitioner’s medical theory was substantiated by the 

government’s medical expert, Dr. Descartes. Dr. Descartes 

explained in her expert report that “[s]eizures induce 

neuro-inflammation, which in turn fosters further seizures; pre-existing neuro-inflammation decreases the seizure threshold, worsening the consequences of seizuretriggering event.” J.A. 309. Additionally, Dr. Descartes 

testified that regardless of the absence of medical literature, viral infections “could very well interact” with a 

DYNC1H1 mutation. J.A. 414. She testified that “when a 

person has an infection, even a cold or a virus or a bacteria 

. . . it’s under stress, definitely, and it could probably affect 

the system.” Id. She further testified that “[i]t’s not uncommon that children that have genetic problems do not 

handle infections better than children that do not have 

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20 SHARPE v. HHS

genetic problems, because . . . the genetic condition they 

have puts them at extra risk of deterioration.” Id. The 

Special Master even acknowledged that the government’s 

expert “allow[ed] that a wild virus infection could constitute an environmental factor that might interact with the 

sequelae primarily stemming from a genetic variant, due 

to a reduced tolerance to infection.” J.A. 26. Given this 

record, in which both parties’ experts agree that vaccinations can adversely interact with a DYNC1H1 gene mutation, the Special Master’s rejection of Petitioner’s medical 

theory was arbitrary and capricious and must be set aside. 

See Paluck, 786 F.3d at 1380. To hold otherwise would effectively require Petitioner to provide conclusive evidence 

linking L.M.’s February 10th vaccinations to her seizure 

disorder, which is not Petitioner’s burden to carry. See Andreu, 569 F.3d at 1378 (holding that the special master 

erred in requiring conclusive evidence in the medical literature linking the DPT vaccine to afebrile seizures). 

C. Loving prong 5

Loving prong 5 requires a petitioner to show “a logical 

sequence of cause and effect showing that the vaccination 

was the reason for the significant aggravation.” Loving, 86 

Fed. Cl. at 144. In other words, Petitioner had to show that 

the vaccinations “did” cause a worsening of the L.M.’s seizure disorder. See id. 

Here, the Special Master acknowledged that L.M.’s 

condition changed for the worse immediately after her February 10th vaccinations. See J.A. 56. The Special Master, 

however, noted that “if L.M.’s seizure activity (like her underlying genetic DYNC mutation) predated vaccination, it 

becomes more difficult to conclude that the February 10th 

vaccinations worsened it.” Id. (emphasis added). The Special Master then concluded that Petitioner failed to meet 

Loving prong 5 because, in part, “it is quite likely that 

L.M.’s seizures in fact began prior to vaccination.” Id. This 

reasoning is erroneous and must be set aside. See Paluck, 

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SHARPE v. HHS 21

786 F.3d at 1380. A significant aggravation claim, by definition, requires a petitioner to have a pre-existing injury. 

Here, L.M.’s pre-existing injury was her seizure disorder. 

See J.A. 18, 55. Thus, that L.M. experienced some seizure 

episodes before receiving her vaccination should have no 

negative affect on Petitioner’s case. In light of this flawed 

reasoning, the Special Master’s finding under Loving prong 

5 must be set aside.5 

D. “Factor Unrelated”

Lastly, Petitioner challenges the Special Master’s finding under the “factor unrelated” inquiry. As noted earlier, 

if a petitioner carries her initial burden to prove causationin-fact, the burden shifts to the government to show by a 

preponderance of the evidence that a “factor unrelated” to 

the vaccine was the “sole substantial factor in bringing 

about the injury.” Hammit ex rel. Hammit v. Sec’y of 

Health & Human Servs., 98 Fed. Cl. 719, 726 (2011), aff’d

sub nom. Stone ex rel. Stone v. Sec’y of Health & Human 

Servs., 676 F.3d 1373 (Fed. Cir. 2012). If the government 

fails to carry its burden, the petitioner is entitled to compensation. See 42 U.S.C. § 300aa–13(a)(1)(A)–(B). 

5 In certain cases, a petitioner can establish a logical 

sequence of cause and effect between a vaccination and the 

injury (Loving prong 5) with a medical opinion to that effect 

where the petitioner has proved that the vaccination can 

cause the injury (Loving prong 4) and that the vaccination 

and injury have a close temporal proximity (Loving prong 

6). See Moriarty ex rel. Moriarty v. Sec’y of Health & Human Servs., 844 F.3d 1322, 1333 (Fed. Cir. 2016). While 

we believe that this is such a case, we hesitate to determine 

that in the first instance. Thus, on remand, the Special 

Master should consider whether Petitioner’s showing under Loving prongs 4 and 6 satisfies Loving prong 5. 

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22 SHARPE v. HHS

Here, the Special Master found that L.M.’s DYNC1H1 

gene mutation was the sole, substantial factor in causing 

L.M.’s seizure disorder. The record does not support this 

finding. 

L.M.’s mutation is located in the stem region of the 

DYNC1H1 gene. The record shows that mutations in this 

region of the gene generally result in non-severe, non-cognitive disorders, such as spinal muscular atrophy with 

lower extremity predominance (a disorder that causes 

weak and poorly coordinated legs). J.A. 8, 24, 53, 373–75, 

412–13, 187–88, 193, 216–17, 221–50. The record also

shows that it was generally the exception for a stem region 

mutation to lead to a severe, cognitive disorder, such as 

L.M.’s seizure disorder. J.A. 8, 19–20, 24, 51–53, 373–75, 

412–13, 216–17. The government’s expert even testified 

that a stem mutation in the DYNC1H1 gene resulting in a 

“severe” outcome is the “exception.” J.A. 397: 13–16. Rather, the evidence in the record indicates that severe cognitive disorders were generally associated with mutations 

in the motor region of the DYNC1H1 gene, a separate region from the stem region. J.A. 8, 19, 24–25, 53–54, 373–

77, 396–97, 410–13, 192–93, 216–18. The Special Master 

acknowledged that the severity of a disorder varies between stem region and motor region mutations. J.A. 54 

(noting that the “location of the mutation affects phenotype”). 

Thus, against this backdrop, there is no substantial evidence to support the conclusion that L.M.’s stem mutation 

was more likely than not the sole, substantial factor causing 

her severe seizure disorder. The science in the record uniformly supports the opposite—a stem mutation in the 

DYNC1H1 gene is generally more likely than not going to 

lead to a non-severe, non-cognitive disorder. Thus, the 

Special Master’s “factor unrelated” finding must be set 

aside as arbitrary and capricious. Paluck, 786 F.3d at

1380. 

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SHARPE v. HHS 23

To uphold the Special Master’s finding would effectively allow the government to prevail under the “factor unrelated” inquiry with mere proof of a gene mutation. As a 

result, children with gene mutations will be shut out from 

the Vaccine Injury Program. Congress did not intend such 

a result. Congress envisioned that children with pre-existing conditions, such as gene mutations, could potentially 

recover. In particular, Congress allowed for significant aggravation theories based on pre-existing conditions: 

in order not to exclude serious cases of illness because of possible minor events in the person’s past 

medical history. This provision does not include 

compensation for conditions which might legitimately be described as pre-existing (e.g., a child 

with monthly seizures who, after vaccination, has 

seizures every three and a half weeks), but is 

meant to encompass serious deterioration (e.g.[,] a 

child with monthly seizures who, after vaccination, 

has seizures on a daily basis).

H.R. Rep. 908, 99th Cong., 2d Sess. Pt. 1 (1986), reprinted 

in USCCAN 6344, 6356–57 (emphasis added). 

In sum, this off-table claim presents the difficult but 

important task of determining whether a child’s receipt of 

vaccinations significantly aggravated her seizure disorder 

in the face of an underlying genetic mutation. Our case law 

is clear that given the complexity of a significant aggravation claim, a petitioner should not be required to disprove 

that a pre-existing genetic mutation caused her significant 

aggravation. Because the Special Master placed this extra 

burden on Petitioner and because the Special Master made 

factual findings unsupported by the record, we vacate the 

Special Master’s denial of Petitioner’s off-table claim and 

remand this claim for further proceedings. 

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24 SHARPE v. HHS

CONCLUSION

We have considered the parties’ remaining arguments 

but find them unpersuasive. For the above reasons, we affirm the Special Master’s denial of Petitioner’s on-table 

claim and vacate and remand the Special Master’s denial 

of Petitioner’s off-table claim for further proceedings. 

AFFIRMED IN PART, VACATED AND 

REMANDED IN PART 

COSTS

Costs to the Petitioner. 

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