\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Adams-Oliver syndrome. About a case}



\author[1]{John Itongwa}%
\author[1]{Moise Colombe}%
\author[2]{Bukuru Hélène}%
\author[2]{Niyongeko Deogratias}%
\author[1]{Cédric Matabaro}%
\author[3]{Fernand Opondjo}%
\author[3]{Viviane Bianga}%
\author[2]{Ndayishimiye Alice}%
\affil[1]{Official University of Bukavu}%
\affil[2]{Université du Burundi}%
\affil[3]{Université Officielle de Bukavu}%


\vspace{-1em}



  
  \date{May 28, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Introduction}

Adams-Oliver syndrome (AOS) is a rare congenital disorder characterized
by congenital cutaneous aplasia of the scalp and terminal transverse
limb anomalies (1). The lesions of congenital cutaneous aplasia are
generally located on the midline of the parietal or occipital regions,
where they may be associated with a parietal bone defect, but may also
appear on the abdomen or limbs(1--3). First described by Adams and
Oliver in 1945, this syndrome also presents severe forms of expression,
including central nervous system anomalies, cardiovascular disease, and
gastrointestinal malformations (1,4--6). Several modes of transmission
have been described: autosomal dominant, autosomal recessive, and
sporadic mutations (7--9). Six genes responsible for Adams-Oliver
syndrome have been identified, including ARHGAP31, RBPJ, NOTCH1, DLL4,
DOCK6, and EOGT (5,10,11). We report the case of a term newborn with
severe intrauterine growth retardation (IUGR) presenting with typical
signs of Adams-Oliver syndrome without associated visceral
complications. This syndrome remains rare and poorly described in the
scientific literature in Burundi.

\textbf{Clinical case}

A male newborn was born by vaginal delivery at 40 weeks in the maternity
ward of the district hospital (MURAMVYA), with severe intrauterine
growth restriction in a polymalformative setting, then transferred the
following day to the neonatology unit of the Kamenge University Hospital
(CHUK) for better management. The multiparous woman was 34 years old,
and denied any toxic exposures or any illness during pregnancy and
family history of the syndrome. The father is 41 years old and a farmer.
The parents denied any prior family hereditary anomalies. She had
attended two prenatal consultations; all the biological tests carried
out releaved no particularities. Two obstetrical ultrasounds had been
performed, but no antenatal anomalies were detected. The newborn was the
5th of 5 apparently healthy siblings. They all come from a
non-consanguineous couple. On initial assessment in the delivery room,
the newborn had a good Apgar and was respiratory and hemodynamically
stable. On admission to the CHUK neonatal unit, evaluation of
anthropometric parameters revealed a low weight of 1500 grams
(\textless{} -3DS), a short stature of 37 cm (\textless{} -3DS) and
microcephaly with a head circumference of 28 cm (\textless{} -3DS).
Physical examination of the head revealed normotensive, pulsatile
fontanelles and a 5x5 cm of aplasia cutis congenital in the left
parietal region, associated with superficial dilatation of the scalp
veins (fig. Ia). Hyperthelorism and dysmorphia facial were noted.
Examination of the limbs revealed brachydactyly associated with
hypoplasia of all fingers except the thumb and index finger of the right
hand (fig. IIa); the thumb and small finger of the left hand (fig. IIb).
In the right foot, amniotic amputation of the large toe with nail
agenesis was also observed (fig. IIc). In the left foot, we observed
nail agenesis, syndactyly amputation of the large and 3rd toes with
clinodactyly of the 2nd toe and small finger with brachydactyly of the
median with index and middle fingers with brachydactyly of the ring
finger (fig. IId).

Cardiovascular, pulmonary, and neurological examinations were within
normal limits. Paraclinical examinations were carried out, including
transfontanellar and abdominal ultrasound, with no abnormalities noted,
and X-rays of the limbs, which confirmed the above-mentioned
abnormalities (Figs. IIIa, b, c, d). Medication with antibiotics and
nutrition with maternel milk had been started, and local care of the
aplasia cutis congenital with isotonic saline (NaCl 0.9\%) was applied;
as for the limb abnormalities, no treatment was initiated. After 4 weeks
of hospitalization in neonatology, we observed that the scalp ulceration
was healing and that he was gaining weight (2500g). He was discharged
with follow-up appointments at 3, 6, 9, and 12 months of age, to assess
his weight-for-height and the healing of the aplasia cutis congenital.

\textbf{Evolution}

At 4 months of age, the evolution was marked by a staturo-ponderal gain,
respectively 57 cm and 5 kg (P/T -1.0 DS), microcephaly with a head
circumference of 38 cm (\textless{} - 2 DS) and good skin healing on the
left parietal level, leaving a circumscribed area of alopecia exposed
(fig. Ib). His psychomotor progress was good. Ultrasound examination of
the area of alopecia revealed a bone defect on the left parietal bone
measuring 4.66 cm in diameter (fig. Ic). At 10 months of age, there was
still no staturo-weight gain (weight 6.5 kg, height 65 cm with P/T -1.5
and -1 DS, microcephaly with a head circumference at 42 cm (-3, -2 DS).
Psychomotor development was good, and an appointment was scheduled with
the neurosurgeon for possible skin expansion and cranioplasty.

\textbf{Discussion}

The first description of Adams-Oliver syndrome, in 1945, was attributed
to Forrest Adams and Peter Oliver who gave it their names; described 8
members of one family (1)\textbf{.} It's a rare congenital disorder
characterized by a polymalformative syndrome. Its incidence is estimated
at 0.44 per 100,000 live births (8). It appears to be more common in
women (1,4,5)\textbf{.} Adam-Oliver syndrome combines congenital skin
aplasia (aplasia cutis congenital) with distal limb anomalies. This
syndrome corresponds to type 2 of Frieden's classification (Appendix 1)
(12)\textbf{.} Limb malformations are the important anomalies in ODS,
with an estimated prevalence of 85\%(13)\textbf{.} The most frequently
described anomalies are nail hypoplasia or anonychia, brachydactyly,
polydactyly, syndactyly, and sometimes pseudo-amputation, with the
absence of fingers or toes, or even complete absence of hand or foot in
extreme forms(2). Cutaneous aplasia is the second most frequent anomaly,
observed in 75 to 85\% of cases(2,12). It most often affects the vertex
in the parietal region, and more rarely the abdomen and limbs. In 64\%
of patients with vertex involvement, a bony defect of the underlying
skull is found (4,10,14). The specific etiologies of congenital skin
aplasia are not elucidated, but chromosomal abnormalities, particularly
BMS1, intrauterine infections, and teratogenic agents during pregnancy
are possible causes(4). Our case presented major criteria for ODS,
namely skin aplasia at the vertex with bone defect and distal limb
anomalies. Prenatal complications such as intrauterine growth
retardation, oligohydramnios, or hydramnios are reported in less than
10\% of cases(7,10,15). In our case, severe intrauterine growth
restriction was noted. In the absence of other obvious etiologies, such
as placental or chromosomal, it was thought to be of vascular origin.
Cutis marmorata telangiectasia congenital (CMTC) is described in 20-25\%
of reported cases of SAO(2,15)\textbf{.} It is characterized by dilation
of the veins and capillaries of the cutaneous and subcutaneous tissue,
anastomosing into networks giving a reticulated (or marbled) appearance.
Bluish venous vessels may be visible through transparency, and skin
ulcerations and atrophied areas may be noted in places. CMTC may be
diffuse over the whole body, including the scalp, or limited to one
area. Lesions may remain stable or regress over
time(2,12,14)\textbf{.}It was absent in our case. Cardiac malformations
occur at a frequency of 23\% and can account for the full severity of
the disease (15). The anomalies observed are left-sided obstructive
heart disease, interventricular or interatrial communications, pulmonary
arterial hypertension, and pulmonary venous stenosis (4,16)\textbf{.} In
our case, no congenital heart disease was identified on cardiac
ultrasound. Central nervous system malformations occur with a frequency
of 30\% and can also determine prognosis. A wide variety of anomalies
have been described, including polymicrogyria, microcephaly, cortical
dysplasia, hydrocephalus with subthalamic and periventricular
calcifications, cerebellar hypoplasia, and agenesis of the corpus
callosum(4,17--19)\textbf{.} Other less frequent anomalies have also
been described, such as genitourinary, ophthalmic, and intestinal
anomalies (4,15)\textbf{.} Our patient had no central nervous system
anomalies, as no abnormalities were detected either on neurological
examination or on the transfontanellar ultrasound performed. Several
genes (ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4) have been
identified as linked to this syndrome, but without genotype-phenotype
correlation(5,10,11). The pathophysiological mechanism is not well
elucidated. Because of the various abnormalities observed, the vascular
origin remains the most likely hypothesis, with the main mechanism being
an in-utero thrombotic event causing early interruption of blood
perfusion to the various affected areas(2)\textbf{.} In the absence of a
molecular biology and genetics department at the CHUK, no gene was
identified in our patient. Autosomal dominant (20) and recessive (8,21)
modes of inheritance have been reported, as have sporadic cases
(7,9)\textbf{.} In the absence of family history and molecular studies,
the mode of transmission cannot be determined in our case. Management is
multidisciplinary (13)\textbf{~;} there is no univocal management in the
initial phase, as it depends on the type of congenital cutaneous aplasia
(CCA). In particular, the presence of any associated abnormalities, such
as a cardiac anomaly, must be taken into account, as these will affect
the prognosis. In the case of ACC of the epidermis vertex with bone
aplasia, surgical management is deferred(12)\textbf{.} Constriction
grooves are treated surgically with Z-plastics; multiple amniotic
syndactylies, which are responsible for major functional limitations,
require early treatment before any skeletal deformity occurs. The use of
skin grafts, in addition to local skin plasty, is decided on a
case-by-case basis. Amniotic amputations require few corrective
procedures. Functional prostheses are of little
use(22)\textbf{.}Scarring alopecia of the vertex had not been corrected,
awaiting the neurosurgeon's assessment, let alone the orthopedic burden.

\textbf{Conclusion}

Adams-Oliver syndrome remains a complex, rare congenital disorder, with
very little documented in the scientific literature. It is essentially
autosomal dominant, but recessive and sporadic modes have also been
reported. This multisystem pathology, requiring regular follow-up,
affects the quality of life and can be fatal if internal organs are
affected. This syndrome requires a continuous and comprehensive
multidisciplinary approach, from birth until the best medical, social,
and psychological conditions are obtained.

\textbf{Authors' contributions}

\textbf{John Mambo Itongwa~:} Writing original draft.

\textbf{Moise Mbaluku Colombe~:} Writing original draft.

\textbf{Helene Bukuru~:} Writing, review and editing.

\textbf{Deogratias Niyongeko~:} Writing, editing and editing.

\selectlanguage{ngerman}\textbf{Cédric Irenge Matabaro~:} Writing original draft.

\textbf{Fernand Manga Opondjo~:} Writing, editing and editing.

\textbf{Viviane Feza Bianga~:} Writing, editing and editing.

\textbf{Ndayishimye Alice~:} Supervision.

\textbf{Acknowledgements}

None.

\textbf{Funding}

None.

\textbf{Conflicts of interest}

The authors declare any conflicts of interest.

\textbf{Consent}

Written consent was obtained from the parents.

\textbf{References}

1. Adams FH, Oliver CP. Hereditary deformities in man due to arrested
development. J Hered. 1945;36:3--7.

2. Kojmane W, Hmami F, Atmani S. Adams-Oliver syndrome and cutis
marmorata telangiectatica congenita. Ann Dermatol Venereol.
2019;146(3):223--5.

3. Lehman A, Wuyts W, Patel MS. Adams-Oliver Syndrome Summary Genetic
counseling Diagnosis Suggestive Findings. In: Adam MP, Mirzaa GM, Pagon
RA, et al {[}Internet{]}. GeneReview. University of Washington, Seattle;
2023. p. 1--27. Available from: https://www.ncbi.nlm.nih.gov/books/

4. Baroudi Ihsan, Ola Alakhras, Thaer Douri NA. Adams -- Oliver syndrome
, intestinal obstruction and heart defects\selectlanguage{english} : a case series of aplasia
cutis congenita {[}Internet{]}. Vol. 1, Oxford Med Case Reports. 2022.
p. 20--3. Available from: https://doi.org/10.1093/omcr/omab141

5. Suarez, E., Bertoli, M.J., Eloy, J.D, Shah SP\emph{.} ~Case report
and review of literature of a rare congenital disorder: Adams-Oliver
syndrome.~\emph{BMC Anesthesiol} ~\textbf{21} , 117 (2021).
https://doi.org/10.1186/s12871-021-01339-0

6. Seo J, Kang J, Lee H, Lee D, Sung H, Hwang S. CASE REPORT A Case of
Adams-Oliver Syndrome. Ann Dermatol. 2010;22(1):96--8.

7. Yeo S, Perrot P, Bellier-Waast F, David A, Duteille F. Adams- Oliver
Syndrome. About a case. Chir Main. 2010;29(4):274--6.

8. Temtamy SA, Aglan MS, Ashour AM ZM. Adams-Oliver Syndrome: Further
Evidence of an Autosomal Recessive Variant. Clin Dysmorphol.
2007;16:141--9.

9. Narang T, Kanwar AJ DS. Adams-Oliver syndrome: a sporadic occurrence
with minimal disease expression. Pediatr Dermatol. 2008;25:115--6.

10. Kim M. Wehrens, Frank De Jongh, MP Ter Laak, EM Cornips, RRWJ Van
der Hulst. Treatment of a Large Skull Defect and Brain Herniation in a
Newborn With Adams- Oliver Syndrome. Cureus. 2020; 12(2):e704-7. ~doi:
10.7759/cureus.7047.

11. Stittrich, A. B., Lehman A, Bodian DL, Justin A, Zong Z, Hong L et
al. Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet.
2014;95(3):275--84. doi: 10.1016/j.ajhg.2014.07.011.

12. Belkhou A,~Francois C,~Bennis Y,~Martinot VD,~Guerreschi P. Aplasia
cutis congenita\selectlanguage{english} : update and management. Ann Chir Plast Esthet.
2016;61(5):450-461. ~doi: 10.1016/j.anplas.2016.07.003.

13. Messerer M, Diabira S, Belliard H, Hamlat A. Adams-Oliver\selectlanguage{english} Syndrome:
About a case of minimal expression. Arch Pediatr. 2010;17(10):1460--4.
Available from: http://dx.doi.org/10.1016/j.arcped.2010.07.009

14. Browning JC. Aplasia cutis congenita: approach to evaluation and
management. Dermatol Ther. 2013;26(6):439--44. doi: 10.1111/dth.12106.

15. Lehman A, Wuyts W PM. Adams-Oliver syndrome. In: Pagon RA, Adam MP,
Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al, editors
GeneReviews1, Seattle (WA) Seattle: University of Washington; 2016.

16. Zapata HH,~Sletten LJ,~Pierpont ME. Congenital cardiac malformations
in Adams- Oliver syndrome. Clin Genet. 1995;47(2):80-4. doi:
10.1111/j.1399-0004.1995.tb03928.x.

17. Amor DJ, Leventer RJ, Hayllar S, Bankier A. Polymicrogyria
associated with scalp and limb defects: variant of Adams-Oliver
syndrome. Am J Med Genet. 2000;93(4):328--34. doi:
10.1002/1096-8628(20000814)93:4\textless{}328::aid-ajmg13\textgreater{}3.0.co;2-0.

18. Orstavik KH, Stromme P, Spetalen S, Flage T, Westvik J, Vesterhus
P,~Skjeldal O. Aplasia cutis congenita associated with limb, eye, and
brain anomalies in sibs: a variant of the Adams-Oliver syndrome? Am J
Med Genet. 1995; 59(1):92-5. ~doi: 10.1002/ajmg.1320590118.

19. Meester JAN, Sukalo M, Schroder KC, Schanze D, Baynam G, Borck G, et
al. Elucidating the genetic architecture of Adams--Oliver syndrome in a
large European cohort. Hum Mutat. 2018;39(9):1246--61.

20. Whitley CB,~Gorlin RJ. Adams-Oliver syndrome revisited. Am J Med
Genet. 1991; 40(3):319-26. doi: 10.1002/ajmg.1320400315.

21. Meester JA,~Southgate L,~Stittrich AB,~Venselaar H,~Beekmans
SJ,~Hollander ND et al. loss-of-function heterozygous mutations cause
Adams-Oliver syndrome. Clin Genet. 2015; 97(3):475-82. ~doi:
10.1016/j.ajhg.2015.07.015.

22. Poeuf B, Samson P, Magalon G. Amniotic bridle syndrome, Chirurgie de
la main. 2008;27(1):136--47. Doi : 10.1016/j.main.2008.07.016\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/FIG/FIG}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/FIH/FIH}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/FII/FII}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig/Fig}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

