Different Clinical Phenotypes in Adams-Oliver Syndrome Conservative Approach to Aplasia Cutis: A Report of Two Cases

Abstract

Adams-Oliver Syndrome (AOS) is a rare genetic disease characterized by combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD), often accompanied by defects in scalp and skull ossification. Different clinical phenotypes may be related to variable severity both of aplasia cutis and TTLD, and of minor clinical features as cutis marmorata telangiectatica congenita (CMTC), congenital cardiac defect and vascular anomalies. The treatment is multidisciplinary: dermatologic, orthopedic and surgical consult should be required. It still remains unclear how to treat patients with a large skin defect that can't be closed primarly and may require both surgical and conservative manage-ment. We report two cases of AOS with typical limb defects and an area of aplasia cutis over vertex of the scalp man-aged conservatively with two different dermatologic devices.

Full text

International Journal of Clinical Medicine, 2012, 3, 215-219
doi:10.4236/ijcm.2012.33042 Published Online May 2012 (http://www.SciRP.org/journal/ijcm) 215
Different Clinical Phenotypes in Adams-Oliver Syndrome
Conservative Approach to Aplasia Cutis: A Report of Two
Cases
Francesca Dini1*, Cristina Tuoni 1*, Andrea Nannipieri2, Sara Lunardi1, Rosa Teresa Scaramuzzo1,3,
Laura D’Accavio1, B. Kuppers 1, A. Valetto4, A. Bartalena1, Antonio Boldrini, Paolo Ghirri1,5#
1Neonatology Unit, Mother and Child Department, University Hospital of Pisa, Pisa, Italy; 2Dermatology Unit, University Hospital
of Pisa, Pisa, Italy; 3Scuola Superiore Sant’Anna, Pisa, Italy; 4Cytogenetics and Molecular Genetics Unit, University Hospital of Pisa,
Pisa, Italy; 5Section of Neonatal Endocrinology and Dysmorphology, University Hospital of Pisa, Pisa, Italy.
Email: #pghirri@med.unipi.it
Received January 9th, 2012; revised February 24th, 2012; accepted March 18th, 2012
ABSTRACT
Adams-Oliver Syndrome (AOS) is a rare genetic disease characterized by combination of aplasia cutis congenita (ACC)
and terminal transverse limb defects (TTLD), often accompanied by defects in scalp and skull ossification. Different
clinical phenotypes may be related to variable severity both of aplasia cutis and TTLD, and of minor clinical features as
cutis marmorata telangiectatica congenita (CMTC), congenital cardiac defect and vascular anomalies. The treatment is
multidisciplinary: dermatologic, orthopedic and surgical consult should be required. It still remains unclear how to treat
patients with a large skin defect that can‘t be closed primarly and may require both surgical and conservative manage-
ment. We report two cases of AOS with typical limb defects and an area of aplasia cutis over vertex of the scalp man-
aged conservatively with two different dermatologic devices.
Keywords: Adams-Oliver Syndrome; Aplasia Cutis Congenita; Scalp and Skull Defects; Dermal Regeneration
Template
1. Introduction
Adams-Oliver Syndrome (OMIM 100300) is a rare con-
genital disorder which includes congenital scalp and
skull defects and terminal transverse limb malformations,
but it may present a wide spectrum of physical anomalies
[1]. Diagnosis is based on clinical criteria. Major features
are aplasia cutis congenita (frequently localized over ver-
tex of the scalp with more or less important involvement
of the underlying bone), terminal transverse limb defects
(commonly bilateral but often asymmetric and usually
consisting in terminal reduction defects of fingers and
toes) and family history of AOS. Minor features are cutis
marmorata telangiectatica congenita (CMTC), congenital
cardiac defect and vascular anomalies; this may be asso-
ciated with a number of additional clinical defects in-
cluding neurological abnormalities, growth retardation
and skin tags. The presence of two major features is con-
sidered sufficient for diagnosis. The combination of one
major and one minor feature should place AOS high in
the differential diagnosis of such individuals [2].
The management consists in a difficult multi-disci-
plinary approach aimed primarily at the treatment of the
aplasia cutis. Large skin defects that cannot be closed
primarily present a management dilemma, and may re-
quire skin grafting or flaps, or a combination of both op-
erative and conservative modalities [3].
The mortality rate reported in the literature, mainly at-
tributed to infection, meningitis or bleeding from the
sagittal sinus, is about 20%.
These two cases report are presented to describe two
different methods of conservative managing of both small
and large cutis aplasia.
2. Case Report 1
A full term male presented with aplasia cutis over vertex
of the scalp limited to the skin (1.5 × 1 cm) (Figure 1),
hypoplasia of bilateral fingers and toes, and dystrophy of
all nails. He also had cleft lip and palate, hypertelorism,
wide anterior fontanel and a cutaneous appendage in the
back. Pregnancy was normal and the APGAR score at 5
minutes was 8. The child’s birth weight was 4700 gr with
cranic circumference of 37.5 cm (both > 97˚ centile).
*Dini F. and Tuoni C. must be considered both as first authors.
#Corresponding author
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Different Clinical Phenotypes in Adams-Oliver Syndrome
Conservative Approach to Aplasia Cutis: A Report of Two Cases
216
Family history was not significant and the parents were
non-consanguineous. We performed genetic studies: the
karyotype demonstrated a normal male (46, XY) and the
patient and parents’ CGH-array revealed no microdele-
tion nor microduplication. The combination of ACC and
TTLD allowed the diagnosis of AOS. The MRI revealed
agenesis of the corpus callosum, absence of the pituitary
and dysmorphism of the lateral ventricles and fronto-
mesial cerebral convolutions. Assessment of serum levels
of pituitary hormones was within normal range. To pro-
mote epithelialisation of the aplasia we used a dressing
hydrocolloid (DuoDERM®). With this device, changed
daily, we obtained a complete resolution of the aplasia in
about 1 month. After the discharge, we programmed cleft
lip and palate’s surgical correction during second month
of life. The patient is currently being followed-up by a
multidisciplinary team.
3. Case Report 2
C.D.R., female, was born at 33 weeks of gestational age
for intrauterine growth retardation. At clinical evaluation
the following were observed: complete aplasia cutis over
vertex of the scalp (4.5 cm of maximum diameter) (Fig-
ure 2), which involved epidermis, dermis and subcuta-
neous tissues of the scalp with significant bone defect
and exposition of dura, bilateral hypoplasia of the toes
(Figure 3), syndactyly and brachydactyly of the right
hand and single umbilical artery. No history of AOS,
mental retardation, infections or maternal drugs intake
during pregnancy was reported and the parents were non-
consanguineous. The transfontanellar ultrasonography re-
vealed asimmetry of the ventricles and hyperechoic areas
in the basal ganglia. Patient’s karyotype and patient and
parents’ CGH-array resulted normal. Clinical features
resulted in a diagnosis of AOS. The aplasia cutis was
treated conservatively with a dermal regeneration tem-
plate (INTEGRA®), because of the complete involve-
ment of epidermis, derma and skull (Figure 4). In few
days after the application of Integra, granulation tissue at
the periphery of the lesion started to form, and the defect
progressively and slowly reduced in following days as
granulation tissue continued to migrate to the center of
the defect. The clinical course was not complicated and
the patient was discharged at 41 week of gestational age.
She was inserted in a close follow-up that included the
performance of magnetic resonance imaging (MRI) of
the brain and a surgical consultation to treat the terminal
transverse limb defects. The dermatologic control at 3
months of corrected age showed a reduction of the
maximum diameter of the aplasia cutis (2.5 cm) (Figure
5). At the last dermatologic control (7 months of cor-
rected age) was observed an almost complete resolution
of the aplasia cutis (0.5 cm) (Figure 6). This experience
in management of huge scalp and bone defect with a
dermal regeneration template (INTEGRA®) showed good
scalp repair and no complications attributed to this ap-
proach.
4. Discussion
AOS is a rare genetic condition characterized by aplasia
Figure 1. Patient n 1: aplasia cutis over vertex of the scalp
limited to the skin.
Figure 2. Patient n 2: aplasia cutis over vertex of the scalp
at the birth.
Figure 3. Patient n 2: hypoplasia of the toes.
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Different Clinical Phenotypes in Adams-Oliver Syndrome
Conservative Approach to Aplasia Cutis: A Report of Two Cases 217
Figure 4. Patient n 2: application of a dermal regeneration
template.
Figure 5. Patient n 2: aplasia cutis over vertex of the scalp
at 3 months of corrected age.
Figure 6. Patient n 2: aplasia cutis over vertex of the scalp
at 7 months of corrected age.
cutis congenita with a wide range of scalp defects and
transverse limb malformations.
The disease has been described for the first time by F.
Adams and C. P. Oliver in 1945, in 8 members of the
same family highlighting an autosomal dominant mode
of inheritance with variable expressivity, although reces-
sive patterns as well as sporadic forms often occour. Al-
though the molecular basis of AOS remains unknown, an
alteration of embryonic vascularization has been hy-
pothesized as a possible pathophysiological mechanism.
CGH-array of our patients and their parents didn‘t show
any abnormalities. Neither of our patients had family his-
tory of AOS and results of their chromosomal study were
unremarkable, then we can suppose a sporadic form.
Diagnosis is based on clinical criteria: 2 major features
are sufficient. Our first patient had typical limb defects
and an area of aplasia cutis over vertex of the scalp, lim-
ited to skin. As additional features he exhibited central
nervous system defects (agenesis of the corpus callosum
and absence of the pituitary) and a severe cleft lip and
palate. Near total agenesis or hypoplasia of corpus callo-
sum in AOS have been described, but our patient is the
first one with a complete agenesia [2]. Gingival cleft was
reported in different members of the same family [4] and
right cleft lip and palate in only one case [5]. In the same
way the second patient presented typical limb defects,
but an area of aplasia cutis larger than the first one, which
involved even the underlying structures with exposition
of dura, and less important neurologic anomalies.
The treatment of cutis aplasia remains controversial
because AOS is a rare disease and there is a lack of ex-
perience related to outcomes of different therapeutic
methods.
The goal of treatment is to achieve complete closure of
the defect, avoiding major complications such as menin-
gitis, hemorrhages, and trauma to the brain [6-7]. Re-
ported treatments have included surgical closure, con-
servative management, or a combination of the two [6-8].
Determination of appropriate clinical management during
the early stages of life improves survival and is based on
the size of the defect, presence of an underlying skull
defect, the child’s general condition, and his/her associ-
ated life expectancy [7-9].
Minor lesions can be controlled with conservative
therapy, like dressing regimens (daily changing of moist
sterile gauze and topical and systemic antibiotic therapy)
[7,9,10], hydrocolloids or devices that stimulate tissue
repair processes. This use of nonadherent, atraumatic,
and relatively cheap dressings has been reportedly suc-
cessful for the initial conservative treatment of large de-
fects [11] because it may avoid the potential failure of
skin flap or heterologous graft coverage [12] and it may
maintains dural induction of osseous regeneration [13].
Some authors recommend a combined regimen of con-
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Different Clinical Phenotypes in Adams-Oliver Syndrome
Conservative Approach to Aplasia Cutis: A Report of Two Cases
218
servative and operative treatment in patients with large
defects to decrease the chance of unsuccessful surgical
management [7,8,11,14].
Large lesions with an underlying skull defect and un-
covered brain require early surgery to prevent massive
hemorrhage, infections and sinus thrombosis. There is
still no agreement about the size of scalp lesion appropri-
ate for surgery: some suggest surgery for lesions >1 cm,
others use conservative approach with excellent outcome
for defects >2 cm and others advise skin grafts for sizes
>4 - 5 cm. Surgical regimens include primary closure,
splitor full-thickness skin graft, scalp rotation flaps, peri-
cranial flaps [9], split rib grafts with a latissimus dorsi
muscle flap [7] and a 1stage operation of free flap per-
formed using microsurgical vascular anastomosis [7-13].
Surgery-related risks are hemorrhage, infections, partial
or total graft failure because of the size of the defect or
the associated abnormality of the adjacent skin [9] and
inhibition of the osteogenic potential of the dura mater
which results in poor regrowth of bone [13,14].
To avoid plastic surgery, in selected cases it’s possible
to try a dermal regeneration template (INTEGRA®). In-
tegra is a two-layer skin regeneration system: the outer is
made of silicon film, that protects from infections and
controls both heat and moisture loss; the inner is a com-
plex matrix of cross-linked fibers that acts as a scaffold
to regenerate dermal skin cells.
This device can be used when the cutis aplasia in-
volves a large portion of the dermis and prevents self-
healing of the skin. It can also be a good choice in new-
borns where it’s difficult to obtain a sufficient amount of
skin for autologus grafting.
There is only one case of AOS in which the area of
aplasia cutis was treated successfully with a dermal re-
generation template (INTEGRA®). In this patient the
skull defect was also associated with ruptured dura mater,
closed primarily with braided nylon [3].
In our first patient the exclusive skin involvement al-
lowed to use a simple dressing hydrocolloid. The second
one, instead, required a skin regeneration system because
of the greater defect; this approach showed good scalp
repair and no complications, with a reduction of the size
of the defect from 4.5 cm to 0.5 cm.
Any plastic surgery that might be done to complete
resolution of the lesion, should be easier with less com-
plications.
A dermal regeneration template can be used success-
fully as initial treatment in full-thickness aplasia cutis at
least to reduce the size of defect and to avoid or postpone
plastic surgery and make it easier.
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