IllnessHypophosphatasia, adult, infantile, perinatal lethal; differential diagnosis

NGS +

Sanger

Hypophosphatasia (HPP) manifests itself in six different clinical forms of varying degrees of severity. Perinatal lethal HPP is associated with significant hypomineralisation, leading to hypercalcemia and respiratory failure. Prenatal benign HPP is associated with fetal skeletal manifestations. Fetal HPP is characterised by rickets and bone fragility. In adults, HPP is associated with early loss of adult dentition and stress fractures of the lower limbs in middle age. In its mildest form, only non-specific signs such as muscular and skeletal pain or osteoporosis can occur in adults. Finally, OdontoHPP includes premature exfoliation of the milk teeth and/or severe dental caries. The perinatal form is almost always fatal within days or weeks. Respiratory complications lead to high mortality rates in the infantile form. It is not assumed that life expectancy is affected in the infantile and adult form or in OdontoHPP. HPP is caused by mutations in the ALPL gene coding for alkaline phosphatase. Perinatal and severe infantile HPP are typically inherited as autosomal recessive traits. Prenatal benign, moderate infantile, infantile HPP, adult HPP and odontoHPP can be inherited autosomal recessively or autosomal dominantly. The less severe the disease is, the more likely it is to be inherited as dominant. The range of inheritance patterns partly explains the clinical heterogeneity.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1150/

• Alias: Phosphoethanolaminuria
• Alias: Rathbun disease
• Acampomelic campomelic dysplasia (SOX9)
• Bone mineral density variation QTL, osteoporosis (COL1A1)
• Caffey disease (COL1A1)
• Campomelic dysplasia (SOX9)
• Campomelic dysplasia with autosomal sex reversal (SOX9))
• Cleidocranial dysplasia (RUNX)
• Cleidocranial dysplasia, forme fruste, dental anomalies only (RUNX)
• Cleidocranial dysplasia, forme fruste, with brachydactyly (RUNX)
• Cole-Carpenter syndrome 1 (P4HB)
• Cole-Carpenter syndrome 2 (SEC24D)
• Combined osteogenesis imperfecta + Ehlers-Danlos syndrome 1 (COL1A1)
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (COL1A2)
• Deafness, AD 39, with dentinogenesis (DSPP)
• Dentinogenesis imperfecta, Shields type II, III (DSPP)
• Ehlers-Danlos syndrome, arthrochalasia type, 1 (COL1A1)
• Ehlers-Danlos syndrome, arthrochalasia type, 2 (COL1A2)
• Ehlers-Danlos syndrome, periodontal type, 1 (C1R)
• Ehlers-Danlos syndrome, vascular type (COL3A1)
• Haim-Munk syndrome (CTSC)
• Hajdu-Cheney syndrome (NOTCH2)
• Hypophosphatasia, adult, childhood, infantile (ALPL)
• Neutropenia, severe congenital 1, AD [ELANE-related] (ELANE)
• Odontohypophosphatasia (ALPL)
• Osteogenesis imperfecta, type I, II, III, IV (COL1A1)
• Osteogenesis imperfecta, type II, III, IV (COL1A2)
• Papillon-Lefevre syndrome (CTSC)
• Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome (LIFR)
• Thanatophoric dysplasia, type I, II (FGFR3)