Clinical and molecular characterization and response to
acitretin in three families with Sj
, Atay Vural
, Fulya Akc
ın S. Bag
, Asli G
, Thomas Ruzicka
A. Nazli Bas
Ludwig Maximillians University,
Dermatology and Allergology, Munich,
Adıyaman Besni State Hospital,
University, Istanbul, Turkey,
Neurodegeneration Research Laboratory
i University, Istanbul,
Department of Dermatology and
Allergology, Ludwig Maximillians University,
Conﬂict of interest: None
ogren-Larsson syndrome (SLS) is a rare congenital disorder characterized
by the triad of ichthyosis, spasticity, and mental retardation. Patients are usually referred to
dermatology clinics during infancy. As paraplegia becomes the most debilitating symptom
of the disease within a few years, ichthyosis, although a major burden for the patient, takes
a back seat. Optimum treatment of ichthyosis in these children and the effect of treatment
on different aspects such as severity of the ichthyosis, pruritus, or quality of life of the
patients’ and their caregivers is not well established.
Materials and Methods Genetic background of eight patients from three families
diagnosed clinically with SLS was determined with whole-exome and Sanger sequencing.
Clinical phenotypes, laboratory ﬁndings, magnetic resonance imaging (MRI), and treatment
of the ichthyosis with acitretin were assessed.
Results All patients had the classical triad of Sj
ogren-Larsson syndrome. Genetic analysis
revealed that one patient had a novel c.799-1 (+/+) homozygous splicing mutation in the
ALDH3A2 gene. Other patients had the c.683G>A p.R228H (NM_000382.2) mutation in
the same gene. Other manifestations included skeletal anomalies, enamel hypoplasia,
bilateral T2-hyperintensities in white matter, and moderate–severe pruritus. Acitretin
treatment in a maintenance dose of 0.25 mg/kg/day decreased the severity of ichthyosis in
all children. It increased quality of life signiﬁcantly in all of the children and their caregivers.
Conclusion We conclude that ichthyosis can be treated effectively with low-dose acitretin
in children with Sj
ogren-Larsson syndrome, and this treatment is associated with a
signiﬁcant improvement in the quality of life.
ogren-Larsson syndrome (SLS) is a congenital disorder
caused by the mutations on the ALDH3A2 gene, which encodes
microsomal fatty aldehyde dehydrogenase (FALDH).
tional FALDH cannot catalyze oxidation of long-chain aliphatic
alcohols to fatty acid, and this disturbance in lipid metabolism
causes accumulation of fatty alcohols in the brain and skin,
causing the barrier dysfunction in these organs.
the earliest manifestation of the disease. At birth, skin is ery-
throdermic in most patients, which fades during infancy and
leaves its place to a characteristic yellow-brownish colored,
generalized ichthyosis that is associated with prominent pruri-
Although spastic paraparesis and mental retardation are
generally seen as the major causes of disability in these
patients, pruritic ichthyosis lesions are a major physical, emo-
tional, and social drawback for the patients and their caregivers.
However, studies on the treatment of ichthyosis in SLS are
insufﬁcient owing to rarity of the disease. Acitretin is a retinoid
that is used for treatment of children with psoriasis and other
Several case reports, case series,
and a few studies
pointed out the safety and efﬁcacy of aci-
tretin in children with inherited ichthyosis syndromes, but still
the use of acitretin in children with ichthyosis is subject to
Herein, we report the impact of acitretin treatment on the
ichthyosis and pruritus symptoms, as well as quality of life
(QOL), in eight children with SLS.
Materials and methods
All patients were ﬁrst diagnosed clinically and then mutational
screening was done by molecular methods. Whole-exome
sequencing (WES) was outsourced for three patients in three
ª 2018 The International Society of Dermatology International Journal of Dermatology 2018, 57, 843–848