ARTICLE
Focal dermal hypoplasia (FDH) is a rare syndrome associated with cutaneous,
skeletal, dental, ocular and soft-tissue defects. It was first described
independently by Goltz et al. [1] and Gorlin et al. [2].
The pathogenic mechanism is still illusive. An X-linked dominant mode
of inheritance with early intrauterine death of male subjects has been
assumed [3, 4]. A striking feature of FDH is the occurrence of giant papillomas
of the skin and mucous membranes [1, 5]. We report on a 14 year old girl
with FDH and obstructing papillomatosis of the larynx and hypopharynx.
Case report
The patient is the second child of non consanguineous, healthy parents
and was born after an otherwise normal pregnancy in the 32nd week of gestation.
FDH was diagnosed at birth because of multiple typical malformations predominantly
on the left side of the body. Her skin was affected by multiple linear
and erythematous atrophic areas. She had left sided anophthalmia, a deformity
of the left foot, a syndactyly of the second to fifth toe of the right
foot and dysplastic nails and ear pinnae.
No findings of FDH or miscarriages were present in the family history.
The girl was referred to our hospital at the age of 14 years for dental
surgery and the removal of peri- and intraoral papillomas. She was short
in stature with a height of 156 cm, slightly mentally retarded, but her
internal status was normal. Serum electrolytes, creatinine, ALT (SGPT),
AST (SGOT), haemoglobin, platelet and differential blood count were normal.
She had markedly reduced subcutaneous adipose tissue. Cutaneous manifestations
included hypoplastic and atrophic skin changes, linear and reticular areas
of hypo- and hyperpigmentation following Blaschko's lines, lipomatous
yellowish lesions of fat herniation, teleangiectasias, skin desquamation,
perioral, and sacrococcygeal papillomas as well as papillomas of the oral
cavity (Fig. 1). She also
reported diminished sweating. Hypoplastic nails with longitudinal splitting
and sparse, brittle hair and circumscribed atrophic alopecia were noted.
A hypoplasia of the left half of the face and left sided anophthalmia
with a prosthesis was present (Fig.
2). Visual impairment of the right eye of 30% was diagnosed. The
ear pinnae were low positioned and dysplastic. However no hearing loss
could be substantiated. The carious teeth were malformed, and defects
of the enamel were seen. Thus, a prosthesis for the upper and lower jaw
was necessary. Additional skeletal dysplasia included a scoliosis of the
lumbar spine and a dysfunctional foot deformity necessitating amputation
of the left foot at the age of two years. With the help of an orthopaedic
prosthesis an almost normal gait was possible. Striate osteopathy of the
long bones was present (Fig. 3).
Initial insertion of the tracheal tube for general
anaesthesia was difficult because of laryngeal and subglottic papillomas
and postoperative withdrawal of the laryngeal tube was associated with
a strong resistance. Therefore severe obstruction of the supraglottic
space was anticipated, and extubation did not seem feasible. Subsequent
endoscopy revealed obstruction due to papillomas of the larynx above the
vocal cords and on both sides of the hypopharynx down to the sinus piriformis
(Fig. 4). Extensive papillomatosis
was also seen in the region of the glossoepiglottic valleculae. Histological
examination of the laryngeal papillomas revealed a hyperplastic, non-keratinizing,
squamous epihelium with sparse infiltration of lymphocytes and granulocytes.
Focal parakeratosis was present, but neither dyskeratotic nor koilocytic
cells were seen. The stroma showed fibrovascular cores with ectatic vessels
and hyperplastic lymphatic tissue. These findings were not suggestive
of human papilloma virus (HPV) as a causative origin, but in situ
hybridisation was not performed.
The papillomas could be removed successfully by endoscopic CO2-laser
surgery and electroresection so that extubation became possible without
tracheotomy.
Discussion
FDH is a rare disorder characterised by malformations of mesodermal
and ectodermal tissue [1, 2, 6]. In our patient the skin and skin appendages,
the muscles and skeletal system, the teeth and the eyes were involved.
No involvement of the heart, the kidney and no microcephaly or hernia
was apparent.
Although periorificial papillomas are common [1, 5] papillomas of the
laryngeal mucous membranes have rarely been reported. Several patients
with laryngeal papillomas necessitating tracheotomy in one case [7] and
patients with oesophageal papillomas and stricture of the upper intestinal
tract [8] have been reported. Papillomas are supposed to appear postnatally
and progress in size and number thereafter. The endoscopic resection of
the papillomas by laser-surgery is a well established procedure and is
considered the method of choice. Our patient presented with obstructive
symptoms of the hypopharynx and the larynx at the age of 14 years. Papilloma-masses
of a diameter of up to 5 cm were excised, thus avoiding tracheotomy. After
the surgical intervention the dysphagia, dyspnoe, cough and hoarseness
disappeared promptly. The patient fully recovered and gained six kg weight
in four months.
Histological examination did not indicate an
HPV origin. This is in accordance with other studies done by electron
microscopy, immunohisto-chemical staining with anti-HPV antibody and dot-blot
hybridisation showing no evidence of HPV types 6, 11, 16, 18, 31, 33,
35 infection [9]. Thus antiviral therapy with interferon has no proven
benefit. As the lesions are considered hamartomas with no malignant potency
chemotherapy is not recommended, and a surgical procedure seems to be
the most suitable approach.
Most cases of FDH are sporadic but the preponderance of female cases
and the occurrence of miscarriages and stillbirths suggest an X-linked
disorder with lethal outcome in most affected males [3, 4, 12]. In some
cases a specific gene locus has been identified, e.g. in the region
of 9q32-qter [13, 14]. The few reported cases of males [15] are explained
on the basis of mosaicism or by a new mutation. Mosaicism may occur due
to postzygotic mutation in the X chromosome [16-18] or half-chromatide
mutation of a gamete [4, 19]. A new mutation is assumed in our patient.
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