Rare and unusual case of familial focal dermal hypoplasia (Goltz syndrome) presenting to otolaryngology in the UK

Abstract

Goltz syndrome or focal dermal hypoplasia (FDH), is an X-linked dominant condition which predominantly involves the skin, limbs and eyes. In otolaryngology, FDH has been poorly described, but can result in increased symptoms of obstructive sleep apnoea requiring surgery. There have also been documented cases of mixed severe hearing loss secondary to congenital ossicular anomalies. More frequently, patients present to the ear–nose–throat clinic with symptoms of dysphagia, secondary to papillomatosis. A 36-year-old woman presented with pain, irritation and dysphagia with a known diagnosis of FDH. She was subsequently investigated with an oesophago-gastro-duodenoscopy, Barium Swallow and an MRI neck scan with contrast. Lymphoid hyperplasia was found on investigation and the patient underwent a panendoscopy with CO₂ laser to the lesion with good clinical outcome. This case report highlights the need for multidisciplinary team involvement to ensure full consideration of management options.

Background

Goltz syndrome or focal dermal hypoplasia (FDH), is a rare X-linked dominant condition which involves ectoderm and mesoderm layers due to POCRN mutations affecting Wnt signalling pathway.¹ Ninety per cent of affected individuals are females, as only a subset of FDH males (mosaic type) survive and 95% of those affected are new mutations.¹

The disease involves a range of tissues, predominantly the skin, limbs and eyes. Dermatologically, 95% report hypopigmentation in a reticulated Blaschko-linear configuration while other skin abnormalities include telangectasias (84%); perioral, groin and distal papillomas (63%); alopecia (79%) and nail abnormalities (longitudinal ridging in 84%). Syndactyly (68%), ectrodactyly (68%), leg length discrepancies (57%) and shortening of long bones (52%) are the most common orthopaedic abnormalities reported by the literature.² It is estimated that 77% suffer from opthalmological manifestations which are related to colobomas (chorioretinal (61%) and iris (50%)), micropthalmia (44%), nystagmus (33%) and strabismus (22%).³ FDH also impacts the female reproductive system and female secondary sexual characteristics, so gynaecological referral is indicated. Finally, FDH is noted to have a wide breadth of craniofacial manifestations including soft (68%) and hard (94%) palatal defects, plus dental abnormalities. As there are no specific medical or genetic therapies, treatment is focused on improving symptoms.¹

We present a case of FDH with specific emphasis on the clinical presentation from an otolaryngology perspective.

Case presentation

A 36-year-old woman presented to clinic with a medical history of Goltz syndrome diagnosed in 1999.

She had previously presented to our service with recurrent right-sided papillomatosis affecting her oropharynx and tongue base, which was treated with a panendoscopy and CO₂ laser in 2007 and again in 2010. Histology on both occasions revealed papillomatosis consistent with FDH.

In 2018, she was referred by her general practitioner to otolaryngology with a sore throat, localised irritation and mild dysphagia to solids. She was known to have papillomatous lesions in the right axillary fossa, right side of her body, right hand and genitalia which were attributed to her diagnosis of Goltz syndrome.

On the initial presentation in October 2018, she reported a burning throat sensation with regurgitation of pieces of mucosa. At the time, flexible nasoendoscopy revealed a raspberry size lesion on both sides of the tongue size, larger on the right side. On subsequent review later that month, it was felt that it was pressing on the epiglottis, but was not affecting her glottis or larynx. At this subsequent later review, she had been complaining of worsening sore throat and difficulty swallowing but denied any bleeding, weight loss or any breathing difficulties.

Given the clinical findings of recurrent papillomatosis and in particular the effect on her swallow, she was booked for an elective panendoscopy and laser resection of the tongue base lesion to improve her symptoms and to rule out any malignant pathology.

Investigations

In November 2018, as a result of the recurrent papillomatosis, MRI of the neck with contrast was undertaken which demonstrated prominent soft tissue in the tongue base with signal characteristics most in keeping with lymphoid hyperplasia (figure 1). There was also abnormal soft tissue in the hypopharynx extending from the midline to the into the left pyriform fossa with thickened upper cervical oesophagus.

Figure 1.

MRI delineating soft tissue papilloma at base of tongue.

A barium swallow was undertaken to investigate the dysphagia (figure 2). On comparison to her previous study in 2008, there was minimal progression and the investigation demonstrated a normal oropharyngeal phase of the swallowing mechanism with innumerable intraluminal polypoid filling defects throughout the tongue base, pharynx and the length of the oesophagus. There was a normal oesophageal primary peristaltic wave generated with good forward bolus propulsion but retention of contrast throughout the oesophagus interdigitated between the oesophageal polyps. The study also demonstrated distal oesophageal dysmotility but the gastro-oesophageal junction was normal. Papillomatosis involving the tongue base, pharynx and entire oesophagus was stable.

Figure 2.

Barium swallow demonstrating multiple papillomatous lesions throughout the upper aerodigestive tract.

Gastroscopy in November 2018 showed several ‘raspberry’ polypoidal lesions in the mouth, on the tonsils and at the cricopharynx. It was commented that the oesophagus is virtually covered with these lesions. Distal to the cardio-oesophageal junction, the appearances of the digestive tract were normal up to the second part of the duodenum.

Differential diagnosis

After initial examination and assessment, the following differential diagnoses were:

benign papillomatous lesions secondary to Goltz syndrome, most likely due to her medical history, the current presentation and clinical findings.

Squamous cell carcinoma being a known presentation in this patient and wider sub-group, crucial to be ruled out after histological tissue sampling as a lesion in the aerodigestive tract.

Human papilloma virus-related papilloma or lesions are also common differentials in all patients presenting with these symptoms and clinical findings. Tissue sampling is also required for confirmation or exclusion.

Treatment

Due to the rare nature of the clinical findings and symptoms, this patient was discussed at the national airway multidisciplinary meeting in London in December 2018, who advised that a panendoscopy and resection with CO₂ laser should be undertaken. In addition, it was advised that the patient should receive oral steroids as a trial to assess for regression of symptoms and to assess response. As expected, there was no significant clinical improvement.

Intraoperatively, an AcuPulse 10 W superpulse CO₂ laser was applied to the pedunculated lesion in the left piriform fossae with subsequent bleeding which settled with intravenous tranexamic acid and anaesthesia induced, controlled hypotension (figure 3). Further CO₂ laser was applied to the right tongue base and right tonsillar fossa for debulking of lesion at 20 watts superpulse continuous scanning mode results (figure 4).

Figure 3.

Papillomatous lesion base of tongue pre-intervention.

Figure 4.

Papillomatous lesion base of tongue post-intervention.

The patient remained in hospital for 2 days for pain relief management, and was discharged home with a 1-week course of oral co-amoxiclav 625 mg three times a day, a weaning steroid regime, chlorhexidine gluconate 0.2% mouthwash for 2 weeks and oral analgesia. The patient was scheduled a follow-up clinic appointment to review biopsy results.

Outcome and follow-up

The biopsies that were taken at surgical resection revealed the following:

Left piriform fossa lesion—Sections showed multiple polypoid pieces of hyperplastic squamous mucosa as well as acanthosis and parakeratosis with papillary growth pattern. The papillae displayed fibrovascular cores. There was exocytosis of lymphocytes. Numerous ectatic vascular channels were present. This is in keeping with benign laryngeal papillomatosis, with no dysplasia or malignancy evident.

Right tongue—The squamous mucosa showed a significant diathermy artefact. Dense infiltrate of lymphocytes were present in the subepithelial tissue, but no neoplasia visible.

Following surgical intervention, the patient was much improved and on review in February 2019 reported that in the previous week she was able to eat and drink with no dysphagia. Repeat flexible nasoendoscopy revealed a prominent tongue base as expected, but was much improved compared with the preoperative presentation. The patient will be followed up regularly to ensure no recurrence of symptoms and was also advised to refer her children to paediatric services for assessment.

Discussion

FDH is an extremely rare condition with studies limited to small case series, the largest of which is 19 patients which needs to be taken into consideration when assessing the presenting symptoms. However, FDH should always be considered due to the wide range of clinical manifestations, as mentioned above, including those specific to otolaryngology.

In a study involving 18 individuals with FDH, 93% reported symptoms of obstructive sleep apnoea in comparison to 11.2% of age‐matched controls, which is statistically significant.⁴ This indicates that FDH increases risks of OSA, the same study subsequently finding that 87% of these patients had undergone tonsillectomy with or without adenoidectomy.⁴ Mixed severe hearing loss has been described and associated with FDH in the literatures. In one case, an exploratory tympanotomy revealed congenital ossicular anomalies and facial nerve malformation, therefore emphasising the importance of further otological investigation for this cohort of patients.⁵

There is significant variation in the phenotype of craniofacial lesions. Of those specific to ENT, 15% had cleft lip and cleft palates and 57% had intraoral lipomas or papillomas.⁶ Subsequently, it was shown that 73% had speech problems or difficulty chewing.⁶ Papillomatosis disease secondary to FDH has been reported to cause dysphagia similar to this case, most requiring resection.⁷

It has anaesthetic implications with case reports of papillary lymphoid hyperplasia at the base of tongue creating difficulties in intubation.⁸ With some anaesthetists calling for further recommendations and emphasising the importance of pre-assessment and multidisciplinary team (MDT) discussion (figure 5) prior to surgical intervention.⁹

Figure 5.

Recommendations for members of the multidisciplinary team in the management of Goltz syndrome.

Multiple tumours of the head and neck have also been found (as well as elsewhere on the body) with the largest of these being 6×8 cm in size. After previous failed therapies of dexamethasone spray, curettage and cryotherapy, a Sharplan CO2 laser used in 8 W mode, single pulse with a spot size of 2–1 mm diameter was used with only a small area of recurrence at 6 months requiring repeat therapy.⁵ It is worth noting that these were dermal lesions as opposed to lesions of aero-digestive tract as in this case. However, we achieved very good symptom relieving results using a CO2 laser used with slightly higher power.

Intraoesophageal lesions have been treated in varying ways. Techniques have been described in an adult using argon plasma coagulation over two sessions with a month between sessions. This showed a marked reduction in papillomata with reported regurgitation without dysphagia after 4 months.¹⁰ Argon plasma coagulation technique for oesophageal papillomas in FDH has also been safely described in a child.¹¹ Balloon-assisted radiofrequency ablation has also been described over a 10-cm area within the oesophagus with 4–5 mm projections achieving complete ablation on the second and third treatments.¹²

Although the majority of the descriptions of these papillomatous lesions are benign within the literature, there has been one case of squamous cell carcinoma of the oesphagus reported.¹³ And therefore should be a key consideration in regards to management and specifically follow-up.

Patient’s perspective.

Prior to treatment, my main concern was that I had difficulty with breathing properly at night when lying flat. I also started to notice that I couldn’t eat hard meats, specifically pork or beef as it was getting stuck. Because I had previously had three or four operations, I immediately thought and knew that I probably needed another operation, even before the diagnosis and management recommendation was given to me. My main concerns were the logistics of time away from my young family during the treatment and subsequent recovery period. I am extremely happy following surgery. I am much relieved to be improved in all senses and especially that food is no longer getting stuck. I am aware that this is likely to happen again in the future, and will address them as and when they arise with the correct specialist.

Learning points.

• Consider genetic profiles in recurrent papillomatosis.

• Consider long term follow-up for potential cancerous transformation and further symptomatic management.

• Multidisciplinary team approach to management as highlighted above.

• Referral of family members to appropriate service when diagnosis is confirmed.