Hereditary Fibrosing Poikiloderma with Tendon Contractures, Myopathy, and Pulmonary Fibrosis

Clinical characteristics: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is characterized by the skin findings of poikiloderma (typically beginning in the first six months and mainly localized to the face), hypohidrosis with heat intolerance, mild lymphedema of the extremities, chronic erythematous and scaly skin lesions on the extremities, sclerosis of the digits, and mild palmoplantar keratoderma. Scalp hair, eyelashes, and/or eyebrows are typically sparse. Muscle contractures are usually seen in childhood and can be present as early as age two years. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs. Some adults develop progressive interstitial pulmonary fibrosis, which can be life threatening within three to four years after respiratory symptoms appear. Other features are exocrine pancreatic insufficiency, liver impairment, hematologic abnormalities, relative short stature, and cataract.

Diagnosis/testing: The diagnosis of POIKTMP is established in a proband with early-onset poikiloderma with other findings, especially muscle contractures and/or muscle weakness and a heterozygous missense pathogenic variant in FAM111B identified by molecular genetic testing.

Management: Treatment of manifestations: Dermatologic manifestations are treated with avoidance of excessive sun exposure and use of sunscreens with both UVA and UVB protection; avoidance of excessive heat exposure and control of fever, especially in early childhood; routine management of lymphedema; emollients, topical steroids for eczema-like lesions. For older individuals, pulsed dye laser may be an option for cosmesis of the telangiectatic component of the rash. Physical therapy and exercise to promote mobility and prevent contractures. Use of self-inflating manual-ventilation bag or mechanical insufflation-exsufflation device if needed for lung disease; noninvasive ventilation if needed. Pancreatic enzyme supplementation for pancreatic exocrine insufficiency.

Surveillance: Annual surveillance (or frequency as needed) includes dermatologic examination, physical therapy assessment for muscle weakness and/or contractures, assessment for orthopedic complications (contractures, especially of the Achilles tendon, and scoliosis), pulmonary function testing, serum transaminases (SGOT, SGPT), alkaline phosphatase, gamma-glutamyl transferase, blood ionogram including calcium, TSH, complete blood count with differential), and ophthalmologic examination.

Agents/circumstances to avoid: Excessive sun exposure (may exacerbate the rash), exposure to heat because of heat intolerance.

Genetic counseling: POIKTMP is inherited in an autosomal dominant manner. In approximately 50% of affected individuals, the FAM111B pathogenic variant is inherited and in approximately 50% it is de novo. Each child of an individual with POIKTMP has a 50% chance of inheriting the FAM111B pathogenic variant. Once the FAM111B pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.