Phenotypic and Genetic Properties in Males at Risk for X-linked Hypohidrotic Ectodermal Dysplasia: Evaluation of an Early Diagnosis Technology and Tests to Assess Nutritional Status

As the first exploratory objective for this study, we propose to obtain facial photographs
for use in testing a computer algorithm that recognizes males at high risk for XLHED. While
3D facial profiling has been reported in HED, the technology does not meet the ease-of-use
criteria for a universal screening tool. FDNA (www.fdna.com), a software company with
expertise in the area of facial recognition, is collaborating with the Sponsor in algorithm
development based on 2D photographs not requiring special photographic technologies. All
males at risk for a diagnosis of XLHED and attending the 2012 NFED Family Conference will be
eligible to participate. A short medical questionnaire will verify the clinical
presentation, they will be requested to provide a baby photograph taken at up to 1 month of
age (to be returned at study completion), and a frontal facial photograph will be taken at
the time of study conduct. The anonymized photographs will be transmitted to FDNA for
analysis. A limited number of unaffected controls will be recruited at the 2012 NFED Family
Conference for the photography study, in addition to the control data already available in
the FDNA database.

As a second exploratory objective, a subset of affected males between ages 5 and 25 years
will have the option of having a blood draw for a set of laboratory studies assessing
nutritional status. HED-affected patients in general (including XLHED) are reported to have
evidence of growth restriction (weight for height) in this age range without clear
mechanistic evidence. A screening panel of nutritional laboratory tests has been designed in
collaboration with experts in the field at the University of California, San Francisco
(UCSF). Anonymized samples will be analyzed at UCSF.

Inclusion Criteria:

1. Males of any age who are registered and attending the 2012 NFED Family Conference;

2. Conform to one of the following requirements for providing informed consent/assent:

- if more than 18 years of age, subjects must provide signed informed consent;

- if less than 18 years of age and it is determined that the subject is capable of
providing assent, both the assent of the subject and consent of the parent(s) or
guardian of that subject must be granted. Under this condition, both parents of
the subject should give their permission, unless 1 parent is deceased, unknown,
incompetent, or not available;

- if the subject is incapable of providing assent, the consent of the parent(s) or
guardian of the subject must be granted. Under this condition, both parents
should give their consent, unless 1 parent is deceased, unknown, incompetent, or
not available.

3. As described in Section 3.2 above, subjects must meet one of the following criteria:

- Male subjects of original gender with genetic confirmation of an EDA mutation or
with the clinical characteristics of HED including a history of decreased
sweating;

- Unaffected, healthy male controls.

Exclusion Criteria:

1. Subjects who are not able or are not willing to comply with the procedures of this
protocol.

2. Subjects with any major medical problem that will prevent them from participating in
this study.

3. HED-affected male subjects who have had prior genetic testing confirming they do not
have the X-linked form of the disorder.