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IEMbase 0759: PTDSS1-related phosphatidylserine synthase 1 superactivity

Scope

Field Value
IEMbase ID 759
Nosology 14.5.01.08
Nosology code IEM0667
Gene PTDSS1
External IDs OMIM:151050; ORPHA:2658
Generated mapping AMBIGUOUS; exact alias LMHD matched multiple local subtype entities
Candidate DisMech targets Lenz-Majewski_hyperostotic_dwarfism.yaml
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal dominant record as PTDSS1-related phosphatidylserine synthase 1 superactivity, with alternate name Lenz-Majewski syndrome and abbreviation LMHD. The phenotype signal is extensive and classic for Lenz-Majewski hyperostotic dwarfism: hyperostosis, skeletal dysplasia, dwarfism or short stature, macrocephaly, wide forehead, delayed or enlarged fontanels, brachydactyly, syndactyly, possible absent phalanges, humeral-radial synostosis, skull-base sclerosis, osteopenic epiphyses, metaphyseal hypostosis, cutis laxa, thin skin, cutis marmorata, sparse hair, enamel hypoplasia, choanal atresia or stenosis, anteriorly placed anus, hypospadias, chordee, inguinal hernia, hydrocephalus, corpus callosum agenesis, intellectual disability, hypotonia, sensorineural hearing loss, and failure to thrive.

DisMech phenotype coverage

Lenz-Majewski_hyperostotic_dwarfism.yaml is the correct local target. The generated ambiguity is caused by local Classic and Attenuated subtype entities sharing the LMHD match key, not by uncertainty about the disease file. The DisMech entry models PTDSS1 gain-of-function phosphatidylserine biosynthesis dysregulation, progressive hyperostotic skeletal dysplasia, cutis laxa, short stature, brachydactyly, syndactyly, cranial hyperostosis, craniofacial dysmorphism, intellectual disability, sensorineural hearing impairment, hydrocephalus, seizures, and hyperphosphoserinuria.

Concordance and completeness

Judgement: exact local coverage with subtype-level mapper ambiguity.

The core disease identity, gene, inheritance, and skeletal-cutaneous-neurologic phenotype cluster are strongly concordant. IEMbase is more granular for several malformation and anatomic findings, including corpus callosum agenesis, anteriorly placed anus, chordee, hypospadias, inguinal hernia, choanal stenosis, nasolacrimal duct stenosis, humeral-radial synostosis, osteopenic epiphyses, and skull-base sclerosis. DisMech is stronger mechanistically and explicitly distinguishes classic from attenuated PTDSS1-related LMHD.

Curation actions

  • Treat Lenz-Majewski_hyperostotic_dwarfism.yaml as the exact disease-file mapping.
  • Do not treat the generated ambiguity as a local gap; it reflects local subtype matches.
  • Consider IEMbase's detailed skeletal, craniofacial, genitourinary, and gastrointestinal malformation rows as future phenotype-completeness prompts.