Introduction
Focal dermal hypoplasia, also known as Goltz-Gorlin syndrome (GGS) or Goltz syndrome,
arises from a rare genetic abnormality in the WNT/β-catenin signaling pathway first
described by Goltz et al in 1962.
1
Molecularly, Goltz syndrome is caused by a mutation or deletion in PORCN that occurs
sporadically or through X-linked dominant inheritance. We report on a 17-year-old
patient who presented to our clinic with extensive papillomas on her right foot and
focal dermal hypoplasia. The papillomas were a source of significant pain and prevented
our patient from wearing adequate footwear. She was referred to plastic surgery for
excision and skin grafting because of persistent symptoms that were not adequately
controlled by topical therapy. We report this case because of paucity in the literature
for this cutaneous finding and lack of reports for management.
Case report
A 17-year-old white girl with a history of GGS and a 10-year history of papillomatous
growths on the right foot was referred to the Department of Dermatology at the University
of Texas Medical Branch. On clinical examination, erythematous verrucous papillomas
were present on the right foot on the medial, lateral, and plantar surface of the
third toe and on the medial surface of the fourth toe (Fig 1, A). Examination of the
head found low-set ears, strabismus affecting the left eye, and malocclusion with
dystrophic and absent teeth. Ophthalmic examination found colobomas of the iris and
retina on the left side. The patient's left hand had 5 digits, and the right hand
had 4 digits with bilateral pollicization∗ surgeries and syndactyly releases. Skin
examination found diffuse linear atrophic streaks present on the thighs bilaterally,
diffuse 1-cm patches of atrophic dermis present on both legs, and onychodystrophy
(Fig 2, A and B). Histologic examination of the papillomas present on the distal and
proximal plantar surface of the right third toe showed an inflamed squamous papilloma
without evidence of malignancy.
The patient opted for surgical management comprising near full-thickness excision
of the papillomas with subsequent 2- × 4-cm split-thickness skin graft transferred
from the right thigh (Fig 1, B). At 6-month follow-up, our patient had no recurrence
of the lesions and was pain free.
Discussion
The molecular pathology resulting in GGS was elucidated in 2007 when deletions of
PORCN (Xp11.23) were detected in 2 females.
2
The gene product is a putative membrane-bound O-acetyltransferase found to be involved
in the processing and secretion of Wnt proteins, important signaling molecules in
embryogenesis and carcinogenesis.
3
Although the implicated gene has been identified, there has yet to be a definitive
link between genotype and phenotype. In their 2011 mutation update, Lombardi et al
4
published their PORCN variation database, which currently contains 119 PORCN anomalies
comprising 105 mutations and 14 gene rearrangements.
The wide range of physical manifestations echoes the variability of genetic lesions
resulting in GGS. Although the amount of functional PORCN required for embryonic viability
has yet to be studied, it is thought that the physical variability is related to lyonization
in females; however, physical variability in males has been attributed to tissue mosaicism,
as nonmosaic males show true embryonic lethality.
5
Clinical diagnosis of focal dermal hypoplasia is possible based on previously described
cutaneous and systemic abnormalities, but diagnostic gene sequencing of PORCN may
confirm the presence of this condition.
6
Typical findings in GGS are asymmetric atrophic hypo-/hyperpigmented linear streaks
along the lines of Blaschko on the trunk or extremities, mucocutaneous papillomas,
skeletal abnormalities (ectrodactyly, syndactyly, polydactyly, oligodactyly), and
eye abnormalities (strabismus, coloboma, microphthalmia).
7
Less common features seen in GGS are intellectual impairment (15%); auditory defects;
microcephaly; cleft lip/palate; hypoplastic kidneys; umbilical, inguinal, epigastric,
or diaphragmatic hernias; and congenital heart diseases such as truncus arteriosus.
8
Our patient had multiple fibrovascular papillomas on the right foot. Previous reports
of GGS showed recurrent periorofacial, perineal, vulvar, and perianal distributions
of papillomas as well as esophageal papillomatosis.
9
Extremity papillomas in the setting of focal dermal hypoplasia sparsely populate the
literature, and their management has not been established. One case report described
treatment of recurrent cutaneous papillomas with cryotherapy; however, the papillomas
continued to recur.
10
The papillomas found on our patient are of similar morphology to the papillomas discussed
in the literature; however, in this case their pedal distribution created a nidus
for infection and necessitated further management. Currently, it is unclear if surgical
excision is superior to cyrotherapy in preventing papilloma recurrence, although our
patient did not show recurrence at 6 months.