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Page 264 Morales et al. J Transl Genet Genom 2022;6:257-65 https://dx.doi.org/10.20517/jtgg.2022.01

As evidenced by other conditions that present with similar skin findings, such as congenital hemidysplasia
with ichthyosiform erythroderma and limb defects syndrome or Conradi-Hünermann-Happle syndrome,
[12]
the use of a combined cholesterol/statin topical therapy has been beneficial . It is thought that
methylsterols affect cell cycles leading to skin cell hyperproliferation, causing a physiopathology reminiscent
of psoriasiform dermatitis . Therefore, the proposed mechanism of action for both oral statins and
[7]
cholesterol also applies to topical administration. The cases affected by severe psoriatic dermatitis or related
skin changes have shown a satisfactory response to combined cholesterol/statin topical therapy [6,11] . It is still
not known why some SC4MOL patients do not exhibit severe skin related features. There could be multiple
contributing factors such as residual enzyme function, for example, but this argument does not explain
patients who presented with severe psoriatic dermatitis (cases 3, 4, 6 & 7) despite normal cholesterol levels.
Our proband presented with intermittent perianal dermatitis, initially responding to traditional topical
therapy. This eventually evolved into severe perianal psoriatic dermatitis that successfully responded to
topical cholesterol/statin therapy without further recurrence.

In summary, SC4MOL deficiency is an ultra-rare condition with characteristic clinical features including
microcephaly, cataracts, psoriatic dermatitis and neurodevelopmental problems. This disorder may be
underdiagnosed given that some of these features overlap with other disorders and are relatively non-
specific. In the presence of a mild case exhibiting only cataracts and developmental delay, sterol metabolism
disorders, including SC4MOL deficiency, should be considered in the differential diagnosis, especially
because of the availability of diagnostic testing and medical interventions. Further longitudinal data to
assess the progression of this condition and the efficacy of therapy are needed.

DECLARATIONS
Acknowledgement
We would like to thank Richard I. Kelley, MD, PhD for the design and management of this patient’s statin
therapy, the patient and his family, as well as the team of healthcare providers involved in this patient’s care.

Authors’ contributions
Clinical care, conceptualization, methodology, writing of original draft, review and editing: Morales JA
Clinical care, supervision, review and editing: Curry CJ
Review and editing: Tise CG
Sterol measurements, resources, review and editing: Kratz L
Clinical care, supervision, review and editing: Enns GM

Availability of data and materials
The data that support the findings of this study are available upon request from the corresponding author.
The data are not publicly available due to privacy or ethical restrictions.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.