CUTIS LAXA SYNDROME – IN TWO SIBLINGS
A CASE REPORT
AUTHORS- DR. SUNIL MULGUND 1
AFFILIATION1 :DEPARTMENT OF PAEDIATRICS , VYDEHI INSTITUTE OF MEDICAL SCIENCES AND
RESEARCH CENTRE ,CITY: BANGALORE , STATE: BANGALORE , COUNTRY :INDIA
ABSTRACT:
A 13 year old female child and 7
year old male child who are siblings born to
non consanguineous married couple ,
presented with wrinkling and
hyperextensibility of skin since early
childhood , suspecting collagen deficiency
disorders (Ehler Danlos , Cutis laxa
syndrome , etc..) molecular genetic studies
were conducted, and the results were used
to counsel the parents about the inheritance
pattern of the disease. This case emphasizes
the value of using molecular genetic testing
for definitive diagnosis in patients with
suspected inherited diseases.
BACKGROUND:
Cutis laxa syndrome is
distinguished by the presence of loose and
redundant skin that has a slow rate of
returning to its original position after being
stretched. This condition is often
accompanied by heart valve regurgitation,
as well as other vascular issues, hernias, and
emphysema. It can be inherited in either an
autosomal recessive or dominant fashion.
On the other hand, individuals with Ehlers-
Danlos syndrome (EDS) may also have
skin that is easily stretchable, but in this
case, the skin is hyperextensible and has a
quick rate of returning to its original
position after being stretched. This is a key
difference that sets the skin changes seen in
EDS apart from those observed in cutis
laxa.
CASE DESCRIPTION:
Two siblings one a 13 year old
female child and other a 7 year old male
child born to non consanguineous married
couple , with no significant antenatal and
natal history ,both of them presented with
complaints of wrinkling of skin ,
hyperextensibilty of skin all over the body,
noticed since early childhood by parents.
There was no similar complaints in the
family and developmentally both siblings
were normal. There was history of
abdominal hernia surgeries in both the
siblings . History of repeated easy
bruisibility of skin and scarring of skin was
also present. Height and weight was
appropriate according to the age for both
siblings.
On examination both siblings had
elongated ,old man like facies , large ears
with normal size of the head, skin over the
face appeared loose , fragile and wrinkled
and lower limbs had multiple atrophic scars
secondary to injuries. Skin over the chest
and abdomen too was hyperextensible as
shown in figure 1. Wrist and finger joints
were hyperextensible . There was also
abdominal surgical scar seen post hernia
repair surgery. Elder sibling had genu
valgum deformity with Trendelenburg type
of gait on examination. Other systemic
examination like abdominal , respiratory ,
cardiovascular and central nervous system
for both siblings were normal.
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Figure – 1 , Head to toe findings
Siblings were evaluated further ,
complete blood count , Liver function test ,
Renal function tests were within normal
limits . USG abdomen showed
infraumbilical midline defect . 2 D ECHO
was done which was normal.
Ophthalmological evaluation showed
normal fundus. Chest X ray and Spinal X
ray was normal.
Need of genetic evaluation was
counselled and whole exome sequencing
was done in both siblings which showed
homozygous likely pathogenic variant -
g.(81936194_81936747)_(81937239_?)del
, with autosomal recessive inheritance
caused by substitution in exon 1-2 of
PYCR1 gene , which confirmed the
diagnosis of Cutis laxa type IIIB
(OMIM#614438) (1) , Cutis laxa type IIB ,
(OMIM#612940) (2)
VARIANT DESCRIPTION:
A homozygous mutation in PYCR1
gene in chromosome 17q25.3 , in
locus/gene number 179035 was detected
first by Kunze et al. (1985) (3). Reversade
et al. (4 )(2009) sequenced the PYCR1 gene
and identified homozygosity for mutations
in the PYCR1 gene.
DISCUSSION:
Cutis laxa type is a genetic disorder
that affects multiple body systems and is
inherited in an autosomal-recessive
manner. The hallmark feature of this
disorder is prematurely aged-looking skin,
which appears wrinkled and loose with
reduced elasticity. The single nucleotide
change leads to a missense mutation
adjacent to a splice junction in the gene
encoding pyrroline-5-carboxylate reductase
1 (PYCR1). PYCR1 plays a critical role in
proline biosynthesis.
Proline is an amino acid that plays a
crucial role in the synthesis of collagen,
which is the main structural protein in the
extracellular matrix of connective tissues
such as skin, tendons, and ligaments.
Proline deficiency can cause cutis laxa
syndrome and various other connective
tissue disorders, by impairing the normal
synthesis and cross-linking of collagen,
leading to weak and unstable connective
tissues, resulting in the characteristic loose,
wrinkled appearance of the skin seen in
cutis laxa syndrome.
Cutis laxa is a group of connective
tissue disorders that can affect multiple
organ systems, including the cardiovascular
system, respiratory system, and
musculoskeletal system. One of the
common features of cutis laxa is heart valve
regurgitation and other vascular
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involvement, along with the presence of
hernias and emphysema.
Cutis laxa can be inherited in both
autosomal recessive and dominant fashion,
and there are several different forms of the
disorder. While patients with Ehlers-Danlos
Syndrome (EDS) may also have easily
TABLE – 1 , KEY DIFFERENCES BETWEEN EDS, CLS, AND MARFAN SYNDROME
CHARACTERISTIC EHLERS-DANLOS
SYNDROME
UNDERLYING Genetic mutations
CAUSE affecting collagen
synthesis/structure
INHERITANCE Mostly autosomal
PATTERN dominant, some
recessive
CLINICAL Hypermobile joints,
PRESENTATION stretchy and easily
bruised skin, fragile
blood vessels, and other
symptoms depending on
subtype
SKIN TEXTURE Stretchy, soft, and velvety
JOINT MOBILITY Hypermobile joints and
increased risk of
dislocations
VASCULAR Fragile blood vessels,
COMPLICATIONS increased risk of
aneurysms, and other
vascular complications
depending on subtype
OTHER Gastrointestinal issues,
COMPLICATIONS scoliosis, and dental
problems depending on
subtype
stretched skin, the skin changes in EDS are
characterized by hyperextensibility and
rapid return from distention, which is
different from the loose and wrinkled skin
seen in cutis laxa. Table -1 gives the key
differences between Ehler Danlos
syndrome (5) , Cutis Laxa syndrome and
Marfans syndrome.(6)
CUTIS LAXA SYNDROME MARFAN SYNDROME
Genetic mutations Genetic mutations affecting
affecting elastin fibrillin-1 synthesis/structure
synthesis/structure
Mostly autosomal Autosomal dominant
recessive, some dominant
Loose, sagging skin that Tall stature, long limbs,
may be extra wrinkled, scoliosis, and other skeletal
respiratory issues, and abnormalities, as well as
other symptoms cardiovascular and eye
depending on subtype problems depending on
subtype
Loose, sagging, and extra Normal or slightly stretchy
wrinkled
Joint mobility may or may Joint hypermobility without
not be affected increased risk of dislocations
May or may not have Cardiovascular complications,
vascular complications such as aortic aneurysms and
depending on subtype mitral valve prolapse
Respiratory issues, Eye problems, such as lens
hernias, and dislocation and near
developmental delays sightedness, as well as chest
depending on subtype wall abnormalities
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 The management of cutis laxa 4 Reversade B, Escande-Beillard N,
involves regular cardiovascular and . Dimopoulou A, Fischer B, Chng SC, Li
pulmonary follow-up, treating symptoms Y, et al. Mutations in PYCR1 cause cutis
such as hernias and emphysema, and laxa with progeroid features. Nat Genet
avoiding environmental triggers. Plastic [Internet]. 2009 [cited 2023 Apr
surgery may be an option for some 18];41(9):1016–21. Available from:
individuals,but they may not be permanent, https://www.nature.com/articles/ng.413
as the loose skin may reoccur.(7)
5 Phenotypic series - PS130000 - OMIM
. [Internet]. Omim.org. [cited 2023 Apr
18]. Available from:
CONCLUSION: https://www.omim.org/phenotypicSeries/
Cutis Laxa is a rare congenital PS130000
disorder , and currently no effective
treatment is available , but with next 6 Entry - #154700 - MARFAN
generation sequencing-based testing, the . SYNDROME; MFS - OMIM [Internet].
exact mutations could be identified, which Omim.org. [cited 2023 Apr 18]. Available
from:
helped in confirmation of the diagnosis of
https://www.omim.org/entry/154700
the proband, in providing accurate genetic
counselling to the family and in offering
7 FAQ [Internet]. Pitt.edu. [cited 2023 Apr
prenatal diagnosis for their next planned
. 18]. Available from:
pregnancy.
http://cutislaxa.pitt.edu/faq.php
REFERENCES:
1 Entry - #614438 - CUTIS LAXA,
. AUTOSOMAL RECESSIVE, TYPE
IIIB; ARCL3B - OMIM [Internet].
Omim.org. [cited 2023 Apr 18]. Available
from:
https://www.omim.org/entry/614438?sea
rch=614438&highlight=614438

2 Entry - #612940 - CUTIS LAXA,

. AUTOSOMAL RECESSIVE, TYPE IIB;
ARCL2B - OMIM [Internet]. Omim.org.
[cited 2023 Apr 18]. Available from:
https://www.omim.org/entry/612940?sea
rch=612940&highlight=612940

3 Kunze J, Majewski F, Montgomery P,

. Hockey A, Karkut I, Riebel T. De Barsy
syndrome--an autosomal recessive,
progeroid syndrome. Eur J Pediatr
[Internet]. 1985;144(4):348–54.
Available from:
http://dx.doi.org/10.1007/bf00441776

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