A pharmaceutical composition comprising: (a) (i) a polypeptide comprising the structure A-sALP-B, wherein sALP is the extracellular domain of an alkaline phosphatase, A is absent or is an amino acid sequence of at least one amino acid, and B is absent or is an amino acid sequence of at least one amino acid, wherein the amino acid sequence of said sALP comprises or consists of the amino acid sequence of SEQ ID NO: 1205; (ii) a polypeptide comprising the structure C-sALP-D-Fc-E or the structure C-Fc-D-sALP-E; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, wherein, optionally, D is two amino acid residues and/or leucine-lysine, and E is absent or is an amino acid sequence of at least one amino acid; or (iii) a polypeptide comprising the structure C-sALP-D-Fc-G-I n -H or the structure C-Fc-D-sALP-G-I n -H; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, G is absent or is an amino acid sequence of at least one amino acid, H is absent or is an amino acid sequence of at least one amino acid, and I is an aspartic acid or a glutamic acid, and n=10 to 16; and (b) a pharmaceutically acceptable excipient; for use in a method of treating one or more bone manifestations of a neurocutaneous syndrome in a subject. (a) (i) a polypeptide comprising the structure A-sALP-B, wherein sALP is the extracellular domain of an alkaline phosphatase, A is absent or is an amino acid sequence of at least one amino acid, and B is absent or is an amino acid sequence of at least one amino acid, wherein the amino acid sequence of said sALP comprises or consists of the amino acid sequence of SEQ ID NO: 1205; (ii) a polypeptide comprising the structure C-sALP-D-Fc-E or the structure C-Fc-D-sALP-E; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, wherein, optionally, D is two amino acid residues and/or leucine-lysine, and E is absent or is an amino acid sequence of at least one amino acid; or (iii) a polypeptide comprising the structure C-sALP-D-Fc-G-I n -H or the structure C-Fc-D-sALP-G-I n -H; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, G is absent or is an amino acid sequence of at least one amino acid, H is absent or is an amino acid sequence of at least one amino acid, and I is an aspartic acid or a glutamic acid, and n=10 to 16; and (i) a polypeptide comprising the structure A-sALP-B, wherein sALP is the extracellular domain of an alkaline phosphatase, A is absent or is an amino acid sequence of at least one amino acid, and B is absent or is an amino acid sequence of at least one amino acid, wherein the amino acid sequence of said sALP comprises or consists of the amino acid sequence of SEQ ID NO: 1205; wherein sALP is the extracellular domain of an alkaline phosphatase, A is absent or is an amino acid sequence of at least one amino acid, and B is absent or is an amino acid sequence of at least one amino acid, A is absent or is an amino acid sequence of at least one amino acid, and B is absent or is an amino acid sequence of at least one amino acid, wherein the amino acid sequence of said sALP comprises or consists of the amino acid sequence of SEQ ID NO: 1205; (ii) a polypeptide comprising the structure C-sALP-D-Fc-E or the structure C-Fc-D-sALP-E; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, wherein, optionally, D is two amino acid residues and/or leucine-lysine, and E is absent or is an amino acid sequence of at least one amino acid; or C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, wherein, optionally, D is two amino acid residues and/or leucine-lysine, and E is absent or is an amino acid sequence of at least one amino acid; or (iii) a polypeptide comprising the structure C-sALP-D-Fc-G-I n -H or the structure C-Fc-D-sALP-G-I n -H; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, G is absent or is an amino acid sequence of at least one amino acid, H is absent or is an amino acid sequence of at least one amino acid, and I is an aspartic acid or a glutamic acid, and n=10 to 16; and C is absent or is an amino acid sequence of at least one amino acid, D is absent or is an amino acid sequence of at least one amino acid, G is absent or is an amino acid sequence of at least one amino acid, H is absent or is an amino acid sequence of at least one amino acid, and I is an aspartic acid or a glutamic acid, and n=10 to 16; and (b) a pharmaceutically acceptable excipient; for use in a method of treating one or more bone manifestations of a neurocutaneous syndrome in a subject.