Lenz Majewski hyperostotic dwarfism

Alternate names

Lenz-Majewski syndrome; Lenz-Majewski hyperostotic dysplasia; Multiple congenital anomalies, mental retardation and progressive skeletal sclerosis; Hyperostotic dwarfism Lenz-Majewski type

Definition

An extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.

Epidemiology

Nine cases have been reported in the literature.

Cause

• LMHD disclosed that all carried one of three heterozygous missense mutations in PTDSS1 encoding phosphatidylserine synthase 1 (PSS1). .
• PSS1 promotes the biosynthesis of phosphatidylserine (PTDS), which is a functional constituent of lipid bilayers.
• In vitro, these PTDSS1 mutations were gain-of-function and increased PTDS production.
• Notably, PTDS binds calcium within matrix vesicles to engender hydroxyapatite crystal formation, and may enhance mesenchymal stem cell differentiation leading to osteogenesis.

Inheritance

The elevated age of some patient's fathers of the reported families is suggestive of an autosomal dominant de novo mutation.

Signs and symptoms

• Marked hypertelorism and broad forehead are noted in all patients as well as large ears.
• Loose and wrinkled atrophic skin with prominent veins is also apparent, giving the patient a progeroid appearance.
• Increasing generalized osteosclerosis of tubular bones, vertebrae and cranial bones is a characteristic feature.
• Cutaneous syndactyly of 2nd to 5th fingers was observed in all patients, as well as brachydactyly and proximal symphalangism .
• All patients have moderate to severe intellectual deficit.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal cortical bone morphology
• Abnormality of dental enamel(Abnormal tooth enamel)
• Abnormality of the metaphysis(Abnormality of the wide portion of a long bone)
• Aplasia/Hypoplasia of the skin(Absent/small skin)
• Aplastic clavicle(Absent collarbone)
• Brachydactyly(Short fingers or toes)
• Broad forehead(Increased width of the forehead)
• Choanal atresia(Blockage of the rear opening of the nasal cavity)
• Delayed cranial suture closure
• Delayed skeletal maturation(Delayed bone maturation)
• Facial hyperostosis(Enlargment of the facial bones)
• Finger syndactyly
• Global developmental delay
• Hypertelorism(Wide-set eyes)
• Intellectual disability(Mental deficiency)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Large fontanelles(Wide fontanelles)
• Macrocephaly(Increased size of skull)
• Macrotia(Large ears)
• Mandibular prognathia(Big lower jaw)
• Osteopetrosis(Harder, denser, fracture-prone bones)
• Prematurely aged appearance(Precociously senile appearance)
• Redundant skin(Loose redundant skin)
• Severe short stature(Dwarfism)
• Short palm
• Specific learning disability
• Symphalangism affecting the phalanges of the hand(Fused finger bones of the hand)
• Thickened calvaria(Increased thickness of skull cap)

30%-79% of people have these symptoms

• Abnormal nasolacrimal system morphology
• Abnormality of the metacarpal bones(Abnormality of the long bone of hand)
• Cryptorchidism(Undescended testes)
• Elbow ankylosis
• Epispadias
• Facial palsy(Bell's palsy)
• Femoral hernia
• Hypospadias
• Inguinal hernia
• Thick vermilion border(Full lips)
• Wide mouth(Broad mouth)

References

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NIH genetic and rare disease info

• NIH info on Lenz Majewski hyperostotic dwarfism

Lenz Majewski hyperostotic dwarfism is a rare disease.

Lenz Majewski hyperostotic dwarfism Resources
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