|Year : 2018 | Volume
| Issue : 2 | Page : 23-26
Inherited systemic hyalinosis: Role of surgery
Saad Al Shammari1, Swathi Velagapudi2, Thomas Varghese Mannil1, Sarvani Davuluri3, Suresh Velagapudi1
1 Departmentof Otolaryngology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 NRI Medical College, Mangalagiri, India
3 Department of Dermatology, Mamata Medical College, Khammam, India
|Date of Web Publication||24-Apr-2019|
Dr. Suresh Velagapudi
Consultant Otolaryngologist, MBC 47, Department of Otolaryngology, King Faisal Specialist Hospital, Riyadh, 11211
Source of Support: None, Conflict of Interest: None
Inherited systemic hyalinosis is a rare autosomal recessive disorder affecting the mutation in gene ANTXR2. Since this entity was first described in 1978, many authors tried to differentiate two distinct entities: severe form as infantile systemic hyalinosis and milder form as juvenile hyaline fibromatosis. As more cases beginning to appear, it was recognized that these two entities are two ends of the spectrum of the same disease process. Now, there is a general consensus of grouping these entities together under the term inherited systemic hyalinosis. In this genetic disorder, the role of the surgery is limited to improve the quality of life only. We report a case of inherited systemic hyalinosis who presented to us at the age of 3 years and had surgery at the age of 7 years and 8 years, with a follow-up of 2 years postsurgery.
Keywords: Coblation, infantile systemic hyalinosis, inherited systemic hyalinosis, juvenile hyaline fibromatosis, surgery
|How to cite this article:|
Al Shammari S, Velagapudi S, Mannil TV, Davuluri S, Velagapudi S. Inherited systemic hyalinosis: Role of surgery. Ann Indian Acad Otorhinolaryngol Head Neck Surg 2018;2:23-6
|How to cite this URL:|
Al Shammari S, Velagapudi S, Mannil TV, Davuluri S, Velagapudi S. Inherited systemic hyalinosis: Role of surgery. Ann Indian Acad Otorhinolaryngol Head Neck Surg [serial online] 2018 [cited 2019 May 24];2:23-6. Available from: http://www.aiaohns.in/text.asp?2018/2/2/23/256992
| Introduction|| |
Inherited systemic hyalinosis (ISH) is a rare autosomal recessive disorder presenting in two forms: aggressive infantile systemic hyalinosis with mortality before the age of 3 years and indolent juvenile hyaline fibromatosis (JHF). In both these forms, prognosis is poor and the management is mainly aimed at palliation. The role of surgery is very limited, to improve the quality of life only. In few cases where surgery was done, the aim was to improve feeding with gingival reduction and tracheostomy for airway management. Here, we present a case where we had to excise the hyaline deposits in the head to improve the quality of life of the patient. We also discussed the nonrecurrence of the lesion at the operated site in our case.
| Case Report|| |
A Saudi boy presented to us at the age of 3 years, who is known to have infantile systemic hyalinosis diagnosed in 2009. He is a product of consanguineous marriage, with parents being first cousins. His disease started early in the 1st year of life with swellings affecting his mouth and both sides of the head in addition to painful joints with progressive contractures. Before he presented to us, he was treated at another hospital where a full workup was done including the study for a specific gene mutation. He had a mutation in a gene which is called ANTXR2 (also called GNG2 gene). The mutation of this gene would cause excessive accumulation of hyaline substance in different parts of the body. A sibling of this patient who had similar manifestations died at younger age.
He presented to our pediatric rheumatology team, with severe growth retardation and multiple joint deformities with significant tenderness [Figure 1]. He had multiple head and face deformities due to the accumulation of hyaline. He had tongue enlargement, small mouth and gingival hypertrophy [Figure 2], two large swellings on the temporoparietal part of the scalp, and one large ulcerated swelling measuring 15 cm × 18 cm in the occipital area [Figure 3]. Hyperpigmentation of the skin on the extensor aspects of joint areas [Figure 4] and cutaneous nodules over the neck and ears [Figure 5] were noted. He was also failing to thrive with difficulty in oral intake. He was evaluated by our colleagues in medical genetics where counseling was given to the parents for any future pregnancies. The inheritance of this disease is autosomal recessive, so there is a 25% chance in any subsequent pregnancy to have the same disease. Multiple specialist teams are involved in managing this patient. The consensus opinion among the teams was to manage this patient conservatively for supportive care only as the prognosis is poor in such cases.
Progress of the disease
In the progressive course of the disease, the child has visited emergency department multiple times and had multiple admissions with recurrent pulmonary infections and diarrhea. He also developed severe dilated cardiomyopathy with ejection fraction of 33% [Figure 6]. Throughout the course of the disease, his mental and cognitive functions were normal. Severe eczema around the neck area was present. He was bedridden and not able to stand or sit without support. He had progressive gingival hypertrophy and tongue enlargement compromising his airway and causing difficulty in feeding. At the age of 6 years, he had tracheostomy and gastrostomy tube insertion.
When the boy was 7 years old, the hyaline deposit at the occipital are has grown large (15 cm x 12 cm) and ulcerated, resulting in intermittent bleeding. Due to this large mass, it was difficult to take care of tracheostomy care and cleaning around the neck resulted in eczematous reaction in neck folds. Till now, in literature, the surgery for this condition was mainly limited to labial and gingival reduction to facilitate feeding only. There were no previously reported cases of excision of such large lesions. Magnetic resonance imaging scan of the occipital mass showed that the tumor has a clear cleavage plane from the underlying muscle, but no such plane was available at the overlying skin [Figure 7]. We approached cautiously as we did not know whether the tumor is very vascular or not and about infiltrative nature of the tumor into surrounding structures. We used Coblator (Evac 70 XTRA wand with a setting of 7 for coblation and 5 for coagulation).
|Figure 7: MRI scan of the large amorphous hyaline deposit in the Occipital area|
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The child was anesthetized through his tracheostomy. Occipital skin was expanded by the tumor. This skin was elevated from the underlying hyaline tumor. There was no definitive tissue plane of dissection, but an artificial plane could easily be created, taking care not to approach the skin too closely due to the fear of disrupting the blood supply to the skin and causing skin necrosis. The muscular tissues in the occipitoparietal area are diffusely infiltrated with hyaline material, and we could not discern any structures individually. The tumor could easily be separated from the underlying occipital bone. There was diffuse oozing during dissection but no profuse bleeding. Total blood loss was around 200 ml. We trimmed the excessive skin and closed the wound and kept Penrose drain. Postoperative antibiotic (cefazoline 500 mg intravenous Q 8th hourly) was given for 5 days. The child was discharged on the 5th postoperative day after removal of the drain, with uneventful recovery. A year after, this young boy started bleeding from the nodular lesions from pinna of both the ears, and we had to excise both pinnae partially. In 2 years of follow-up, the occipital lesion was stable and there was no recurrence in the operated area [Figure 8]. However, he continued to develop new nodular lesions on other parts of the body. These surgeries were not curative but definitely made much easier for the parents to take care of the child in a difficult condition like this.
|Figure 8: Post excision of the occipital nodule with no local recurrence after 2 years|
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| Discussion|| |
Inherited systemic hyalinosis (ISH) is a rare autosomal recessiive disorder described first in 1978, caused by a mutation in the ANTXR2 gene encoding a transmembrane protein involved in endothelial development. The ANTXR2 (also known as CMG2) locus is on chromosome 4q21. Symptoms of ISH manifest within the 1st months of life as progressive painful joint contractures and edema, hyperpigmentation of the skin, cutaneous nodules, persistent diarrhea with protein-losing enteropathy, and recurrent infections. Many authors have grouped this disorder in to two groups depending on severity of manifestation.,, The severe form called infantile systemic hyalinosis which manifests in early months of life and often dies within 3 years of life. The other milder form is known as JHF develops in older children with indolent course.
Less than 70 cases were reported in the literature. Out of these, more than half (21 cases from Saudi Arabia,, 15 from Iran,,, and 1 from Oman) were reported from Middle East and Persian countries as consanguineous marriages are more common in these areas. Few cases have been reported from India,, as well.
The aim of the management of these patients is toward improving quality of life as there is no known specific treatment. Tracheostomy is often necessary to maintain the airway at the time of the surgery or even otherwise as intubation in these cases is extremely difficult. Gingivectomy and reduction of labial tissue were performed to facilitate oral feeding and to improve oral hygiene and overall appearance. Excision of large nodular lesions can be done safely without major blood loss and can easily be dissected out to improve the quality of life in these patients. We did not notice any recurrence of the lesions in the operated site even though new lesions have appeared in other sites. In a report of a patient with a 10-year follow-up, the authors have noted severe blood loss during excision of the lesions and also recurrence in the operated areas subsequently. In the above case, authors have used scalpel to cut the lesions whereas we have used Coblator for dissection and may be that has contributed to reduced blood loss in our case. These children are prone to recurrent infections due to severe malnutrition and protein-losing enteropathy. Hence, it is prudent to use antibiotic coverage in the perioperative period.
The other supportive measures include physiotherapy and nutritional support. Treatment with oral nonsteroidal anti-inflammatory drugs, intralesional steroid injection, and use of methotrexate have yielded disappointing results. Oral D-penicillamine might improve joint flexibility in few cases. Overall prognosis is poor.
| Conclusion|| |
Inherited systemic hyalinosis is an autosomal recessive disorder depositing hyaline substance in the tissues with varying severity. No definitive treatment is available and has poor prognosis. Surgery is limited for functional rehabilitation only.
If surgery is needed for removal of hyaline deposits, it can be done with minimal blood loss when using cautery, Coblator, or laser. No natural tissue planes could be identified, but artificial planes could be created easily. Postoperative period should be covered with appropriate antibiotics.
Recurrences and new lesions are expected to appear after the surgery.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]