Case for diagnosis

Abstracts

Fibromatose hialina juvenil e hialinose sistêmica infantil são desordens autossômicas recessivas, raras da infância. À histologia, há depósito de material hialino na derme e subcutâneo. As características clínicas principais são: lesões pápulo-nodulares, hipertrofia gengival, contratura articular, lesões ósseas osteolíticas e retardo no crescimento. Mutações no mesmo gene foram identificadas nas duas condições, sugerindo que sejam espectros da mesma doença.

Fibroma; Hipertrofia gengival; Mutação; Pele; Pele

WHAT IS YOUR DIAGNOSIS?

Case for diagnosis^*

Flávia Vieira Brandão^I; Cláudia Márcia Resende Silva^II; Bernardo Gontijo^III; Antônio Carlos Martins Guedes^IV

^I

^IIDermatologist, Hospital das Clínicas da Universidade Federal de Minas Gerais (UFMG) – Belo Horizonte (MG), Brazil

^IIIAssociate Professor of Dermatology, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG) – Belo Horizonte (MG), Brazil

^IVAssociate Professor of Dermatology, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG) – Belo Horizonte (MG), Brazil

Mailing Address

ABSTRACT

Juvenile hyaline fibromatosis and infantile systemic hyalinosis are rare autossomal recessive disorders with onset in infancy or early childhood. Histological examination shows deposit of hyaline material in the dermis and subcutaneous tissue. Clinical features include papulonodular skin lesions, gingival hypertrophy, flexion contractures of joints, osteolytic bone lesions and stunted

growth. Mutations in the same gene were detected in both conditions, suggesting that they may be variants of the same disorder.

Keywords: fibroma; gingival hypertrophy; mutation; skin; skin/lesions

HISTORY OF THE DISEASE

Two-year nine-month patient, daughter of consanguineous parents, since four months of age she presented facial papules, nodules on the scalp, neck, dorsum and perianal region, articular contracture in flexion and failure to thrive. No report of chronic diarrhea or recurrent respiratory infections. Family history included eight miscarriages before the birth of the patient and two other healthy older brothers. The physical examination showed pearled papules on the perinasal and perioral region, erythematous violet papules and nodules on the neck, scalp, upper dorsum and perianal region (Figure 1). Presence of cutaneous thickness, hyperpigmentation over bone prominences, gingival hypertrophy, articular contracture of upper and lower limbs, in frog-leg position (Figure 2) and delayed growth, with weight and height percentile below 3. No significant impairment of mental development. Laboratory tests were within the normal range, long bone x-ray showed osteopenia and biopsy of two nodules showed hyaline, amorphous and eosinophilic material on the dermis (Figure 3).

COMMENTS

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare hereditary disorders of autosomal recessive character and unknown etiology.

The onset of clinical manifestations of JHF is normally three to four months of life ¹, and ISH is typically manifested in the first weeks to months of life ². In both disorders, mental development is normal ^1,3.

In JHF, lesions may be pearled papules on the face, neck and especially on retroauricular and perinasal regions, large tumors, especially on the scalp, trunk and limbs and perianal plaques or nodules. Gingival hypertrophy is common, impairing eating. Bone manifestations include osteolytic lesions, especially in distal phalanges and metaphyses, cortical thinning and generalized osteopenia ^1-5. There are reports of scoliosis, macrocephaly and reduced weight and height ^1,3.

In ISH, in addition to cutaneous lesions, there is articular contracture, gingival hypertrophy and bone abnormalities, skin is thick, with hyperpigmentation over bone prominences. Patients progress with persistent diarrhea, recurrent infections and death within the first two years of life¹.

Histopathology of skin lesion is diagnostic, characterized by dermal deposits of amorphous, hyaline and eosinophilic material ⁵. Microscopic findings of ISH and JHF are similar. However, ISH has deposits of hyaline material in other organs as well, such as gastrointestinal tract, adrenal glands, bladder, skeletal muscles, thymus and parathyroid ¹. Even though many theories have been proposed, there is no consensus about the origin and nature of the hyaline material ^1,3,5.

In 2002, Rahman et al. mapped the gene of JHF in chromosome 4q21. Recently, Dowling et al. and Hanks et al. showed the presence of deleterious mutation of the gene in capillary morphogenesis (CMG2), located in chromosome 4q21, both in juvenile hyaline fibromatosis and in infantile systemic hyalinosis ^1,3,4.

Owing to the similarities between these two conditions, Shehad et at. proposed that they would represent different manifestations of the same disorder and the term systemic hyalinosis could then be used for both conditions, maintaining the term infantile systemic hyalinosis for early and severe forms and juvenile systemic hyalinosis for mild and moderate forms ².

Differential diagnosis of JHF/ ISH includes Winchester syndrome, infantile multicentric neurofibromatosis, lipoidproteinosis and mucopolysaccharidosis type 2 ^3,4.

Treatment of these lesions consists in surgical excision. However, this practice may be disabling and recurrences are frequent ^1,3,5.

REFERENCES

• 1.  Al-Najjadah I, Bang LR, Ghoneim IE, Kanjoor JR. Infantile Systemic Hyalinosis. J Craniofac Surg. 2003;14:719-723.
• 2.  Shehad ZP, Raafat F, Proops DW. Juvenile Hyaline Fibromatosis. Int J Pediatr Otorhinolaryngol. 1995;33:179-86.
• 3.  Muniz ML, Lobo AZC, Machado MCMR, Valente NYS, Kim CA, Lourenço SV, et al. Exuberant Juvenile Hyaline Fibromatosis in Two Patients. Pediatr Dermatol. 2006; 23:458-64.
• 4.  Antaya RJ, Cajaiba MM., Madri J, Lopez MA, Ramirez MCM, Martignetti JA, et al. Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis Overlap Associated With Novel Mutation in Capillary Morphogenesis protein-2 Gene. Am J Dermatopathol. 2007;29:99-103.
• 5.  Ramos AMCR. Contribuição ao Estudo da Fibromatose Hialina Juvenil [Tese]. Belo Horizonte(MG): Universidade Federal de Minas Gerais; 1994.105 p.

Publication Dates

• Publication in this collection
  25 Feb 2010
• Date of issue
  Dec 2009

History

• Accepted
  27 Dec 2008
• Received
  20 Dec 2008