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
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common features of cutis laxa is heart
valve regurgitation and other vascular
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-
TABLE – 1 , KEY DIFFERENCES BETWEEN EDS, CLS, AND MARFAN SYNDROME
CHARACTERISTI EHLERS-DANLOS
C 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
Danlos Syndrome (EDS) may also have
easily 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 http://dx.doi.org/10.1007/bf00441776
involves regular cardiovascular and   
pulmonary follow-up, treating symptoms 4 Reversade B, Escande-Beillard N,
such as hernias and emphysema, and . Dimopoulou A, Fischer B, Chng SC, Li
avoiding environmental triggers. Plastic Y, et al. Mutations in PYCR1 cause cutis
surgery may be an option for some laxa with progeroid features. Nat Genet
individuals,but they may not be [Internet]. 2009 [cited 2023 Apr
permanent, as the loose skin may reoccur. 18];41(9):1016–21. Available from:
(7) https://www.nature.com/articles/ng.413
  
5 Phenotypic series - PS130000 - OMIM
. [Internet]. Omim.org. [cited 2023 Apr
CONCLUSION:
18]. Available from:
Cutis Laxa is a rare congenital https://www.omim.org/phenotypicSeries/
disorder , and currently no effective PS130000
treatment is available , but with next   
generation sequencing-based testing, the 6 Entry - #154700 - MARFAN
exact mutations could be identified, which . SYNDROME; MFS - OMIM [Internet].
helped in confirmation of the diagnosis of Omim.org. [cited 2023 Apr 18].
the proband, in providing accurate genetic Available from:
https://www.omim.org/entry/154700
counselling to the family and in offering
  
prenatal diagnosis for their next planned
pregnancy. 7 FAQ [Internet]. Pitt.edu. [cited 2023 Apr
. 18]. Available from:
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].
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https://www.omim.org/entry/614438?
search=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?
search=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
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