Acta Dermato-Venereologica 99-1CompleteContent | Page 31
SHORT COMMUNICATION
A Case of Ankyloblepharon-ectodermal Defects-cleft Lip/Palate-syndrome with Choanal Atresia and
Skin Erosions: Phenotypic Variability of TP63-related Disorders
Luana NICULESCU 1,2 , Matias WAGNER 3,4 , Dominik S. WESTPHAL 4,5 , Marcus FISCHER 6 , Walter MIHATSCH 7 , Anke
PROTHMANN 8 , Thomas RUZICKA 1 , Andreas WOLLENBERG 1 , Hans WOLFF 1 , Heinrich SCHMIDT 9 and Kathrin A. GIEHL 1,2 *
1
Department of Dermatology and Allergy, 2 Center for Rare and Genetic Skin Diseases, Department of Dermatology, 6 Department of Pediatric
Cardiology and Pediatric Intensive Care Medicine, Ludwig Maximilian University, Frauenlobstrasse 9–11, DE-80337 Munich, 3 Institute of
Neurogenomics and 4 Institute of Human Genetics, Helmholtz Zentrum Munich, Neuherberg, 5 Institute of Human Genetics, Technical University
Munich, Munich, 7 Department of Pediatrics, HELIOS Klinikum Pforzheim, Pforzheim, 8 Department of Pediatrics, Harlaching, Munich Municipal
Hospitals, Munich, and 9 Department of Pediatrics and Medical Genetics, Dr. von Hauner Children’s Hospital, Ludwig Maximilian University,
Munich, Germany. E-mail: [email protected]
Accepted Jun 26, 2018; Epub ahead of print Jun 29, 2018
Ankyloblepharon-ectodermal defects-cleft lip/palate
(AEC) syndrome is an autosomal dominant disease. AEC
was first described by Rapp & Hodgkin in 1968 in a family
in which the patients presented the same clinical traits
(1). Until now, differentiation between AEC and Rapp-
Hodgkin syndrome (RHS) has been made by the presence
of ankyloblepharon and midfacial hypoplasia, respectively
(2, 3). However, as has been stated previously, differen-
tiation between AEC and RHS should be abandoned in
favour of a more inclusive term (4).
TP63 encodes the p63 protein, which is essential for the
maintenance of epidermal stem cells. Furthermore, p63
takes part in the morphogenesis and maintenance of the
epidermis. It regulates the proliferation and differentia-
tion of keratinocytes. Mutations in TP63 also cause other
syndromes, such as acro-dermato-ungual-lacrimal-tooth
syndrome (ADULT), ectrodactyly–ectodermal dyspla-
sia–cleft syndrome (EEC syndrome), split-hand/split-foot
malformation type 4 (SFHM4), limb-mammary syndrome
(LMS) and isolated cleft lip/cleft palate (CL/P) (5).
CASE REPORT
111
A newborn girl was referred to the Center for Rare and Genetic
Skin Diseases from the Department of Pediatrics of Harlaching,
Municipal Hospital, Munich, Germany . She was the 2 nd child of
healthy, non-consanguineous parents of Caucasian origin, and
was born at 41+1 weeks by vaginal delivery. At birth her weight
was 3,530 g (45 th centile), length 54 cm (79 th centile) and head
circumference 37 cm (91 th centile). At birth, she presented with
generalized erythema and widespread superficial skin erosions on
the lumbosacral region (Fig. 1a). The girl had facial deformity,
including midfacial hypoplasia, bilateral ectropion, small nasal
bridge, long philtrum, microstomia and nail hypoplasia.
Despite the striking clinical findings, she was in good general
health with no raised inflammatory markers. After 10 days she
developed difficulty suckling. A nasal-gastric catheter could not be
passed through the nostrils, therefore magnetic resonance imaging
(MRI) was performed. This confirmed the presence of bilateral
bony choanal atresia. Several surgical interventions were perfor-
med to correct the defect. Her renal function was normal, but a
renal pelvis dilatation was identified, which could lead to urinary
dysfunction or even obstruction. The lumbosacral erosions healed,
but new erosions with crusts appeared on the fronto-parietal scalp
(Fig. 1b). By 3 months the girl’ growth was normal; length 57 cm
(45 th centile) and weight 5,180 g (29 th centile).
At the age of 6 months the erosions on her scalp improved and
white, wiry hair was observed. Trichoscopy revealed a lack of
Fig. 1. (a) Generalized erythema of the skin and multiple erosions on the
lumbosacral region. (b) Erosions of the scalp. (c) Erosions of the scalp with
sparse, white wiry hair. (d) Dark pigmented teeth. Permission to publish
these photographs are given by the patient’s parents.
pigment. At the age of 11 months new erosions appeared on the
scalp as well as diffuse alopecia (Fig. 1c). The fingernails and toe
nails had developed from hypoplastic (Fig. S1a, b 1 ) to dystrophic
(Fig. S1c 1 ), and the appearance of dark pigmented teeth was noted
(Fig. 1d). During follow-ups bacterial swabs were taken from
the scalp and showed massive colonization with Staphylococcus
aureus, which was treated with topical antibiotics (fusidic acid),
in combination with betamethasone, and antiseptic measures with
polyhexanide.
To summarize the clinical findings: the young patient presented
at birth and at 1 month with skin erosions on the scalp, nail dyspla-
sia, teeth anomalies, genitourinary deformities and choanal atresia
(Table SI 1 ). As in the first weeks, many of the clinical findings
were not yet present, and because they could not be attributed to a
specific syndrome, single exome sequencing was performed. The
previously published heterozygous missense variant c.1790T>C,
p.(lle597Thr) was identified in the TP63 gene, which has been
described previously in a patient with AEC syndrome (5). The
variant was not listed in 120,000 control alleles of the Exome
Aggregation Consortium (ExAC)-Browser and it was predicted to
change a conserved amino acid. The de novo status was confirmed
by carrier testing of the unaffected parents. The variant could not be
identified in blood DNA from the parents using Sanger sequencing.
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2997
1
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-2997
Acta Derm Venereol 2019; 99: 111–112