IllnessHyaline fibromatosis syndrome, differential diagnosis

NGS +

In hyaline fibromatosis syndrome (HFS) hyaline deposits accumulate in many tissues, including skin, joints, bones and internal organs. The severity of the symptoms falls into a spectrum. In severe cases (infantile systemic hyalinosis), symptoms are present perinatally or begin in the first months of life and can be life-threatening. In milder cases (juvenile HFS), symptoms begin in childhood and affect fewer body systems. A main feature is the growth of benign nodules under the skin, very often on the scalp. In more severe cases, the nodules also appear in muscles and internal organs, causing pain and complications. Severely affected patients may develop protein-losing enteropathy due to nodules in the intestine, which is associated with severe diarrhea, failure to thrive and cachexia. Another common feature of HFS are painful white/pink/pearly skin bumps that often appear on the hands, neck, scalp, ears and nose as well as in joint creases and the genital area. They vary in size, often increasing in size over time. In some affected individuals, especially those with a more severe course, the skin over the joints, such as the knuckles, wrists, elbows and finger joints, is hyperpigmented. HFS is also characterized by gingival hypertrophy, and in some affected individuals the skin is thickened. Joint stiffness and pain are common, and many affected individuals develop contractures. In adulthood, some patients are wheelchair dependent, and bone abnormalities may also occur. Mental development is typically normal. People with milder symptoms live into adulthood, while the most severely affected individuals often do not survive beyond early childhood due to chronic diarrhea and recurrent infections. Mutations in the ANTXR2 gene cause HFS, which is inherited in an autosomal recessive pattern. The diagnostic yield via molecular genetics is not known, and negative DNA testing does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1525/

• Alias: Inherited systemic hyalinosis
• Alias: Molluscum fibrosum
• Alias: Murray syndrome
• Alias: Puretic syndrome
• Allelic: Basal ganglia calcification, idiopathic, 4 (PDGFRB)
• Allelic: Ectopia lentis, familial (FBN1)
• Allelic: Kosaki overgrowth syndrome (PDGFRB)
• Allelic: Marfan syndrome (FBN1)
• Allelic: Myeloproliferative disorder with eosinophilia (PDGFRB)
• Allelic: Osteogenesis imperfecta, type I, II, III, IV (COL1A1)
• Allelic: Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Acromicric dysplasia (FBN1)
• Caffey disease (COL1A1)
• Combined osteogenesis imperfecta + Ehlers-Danlos syndrome 1 (COL1A1)
• Ehlers-Danlos syndrome, arthrochalasia type, 1 (COL1A1)
• Farber lipogranulomatosis (ASAH1)
• Geleophysic dysplasia 2 (FBN1)
• Hyaline fibromatosis syndrome (ANTXR2)
• MASS syndrome (FBN1)
• Marfan lipodystrophy syndrome (FBN1)
• Mucolipidosis II + III alpha/beta (GNPTAB)
• Multicentric osteolysis, nodulosis + arthropathy (MMP2)
• Myofibromatosis, infantile, 1 (PDGFRB)
• Premature aging syndrome, Penttinen type (PDGFRB)
• Stiff skin syndrome (FBN1)
• Urbach-Wiethe disease (ECM1)
• Weill-Marchesani syndrome 2, AD (FBN1)