Congenital protein losing enteropathy (PLE) presents a diagnostic challenge, and can be caused by a group of inherited disorders. Mutations in several genes, including CD55, FOXP3, ANTXR2, DGAT1 and others have been implicated thus far.
We present a case of a 4 months old male infant, who presented for evaluation due to the combination of intrauterine growth retardation (IUGR), multiple fractures and contractures, ascites and dysmorphic features. He was the first child born to consanguineous parents of Arab-Muslim descent. Immediately following his birth, via an elective Cesarean section, bilateral clavicular fractures were noted. He was transferred to Sheba Medical Center at the age of 3 months, and upon physical examination, a unique pattern of hyperpigmentation of the metacarpophalangeal (MCP) joints and medial malleoli was noted, as well as
An extensive investigation ensued, however did not yield a diagnosis. Finally, single whole exome sequencing (WES) was performed for the proband, and had revealed a missense c.155C>T (p.Ser52Phe) mutation in the ANTXR2 gene (also referred to as CMG2) for which the patient was homozygous, establishing the diagnosis of Hyaline Fibromatosis syndrome.
Hyaline Fibromatosis syndrome is a rare autosomal recessive disorder, usually characterized by multiple subcutaneous modules, gingival hypertrophy, joint contractures and hyaline deposition, and in its more severe form is termed Infantile Systemic Hyalinosis (ISH). Protein-losing enteropathy, as well as the typical hyperpigmentation of the MCP joints and malleoli, have also been reported in patients with ANTXR2 mutation. Currently, there is no known targeted treatment for this disorder.
