Lenz-Majewski Hyperostotic Dwarfism (LMHD)

What is Lenz-Majewski Hyperostotic Dwarfism (LMHD)?

This is an incredibly rare genetic condition with just 9 cases reported worldwide to date. The main identifying symptoms of the syndrome include dwarfism, a unique facial appearance, cutis laxa (sagging skin) and progressive bone sclerosis.

The syndrome is also characterized by intellectual disability, which is often quite severe.

This syndrome is also known as:
Hyperostotic dwarfism Lenz-majewski Syndrome

What gene changes cause Lenz-Majewski Hyperostotic Dwarfism (LMHD)?

The PTDSS1 gene is responsible for causing the syndrome. It is inherited in an autosomal dominant pattern.

In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.

What are the main symptoms of Lenz-Majewski Hyperostotic Dwarfism (LMHD)?

The unique facial features of the syndrome include widely spaced eyes, large ears and a broad forehead. A large head and wide fontanelles are also common.

Moderate to severe intellectual disability is a feature of the syndrome in all identified patients.

Other common symptoms include an absent collarbone, abnormal tooth enamel, abnormality of the bones, and delayed bone maturation. Severe growth retardation is another symptom.

Possible clinical traits/features:
Autosomal dominant inheritance, Sensorineural hearing impairment, Wide mouth, Thin skin, Prominent scalp veins, Syndactyly, Kyphosis, Hypertelorism, Cognitive impairment, Hypospadias, Hernia of the abdominal wall, Hydrocephalus, Humeroradial synostosis, Broad forehead, Hyperextensibility of the finger joints, Short stature, Cryptorchidism, Cutis marmorata, Cutis laxa, Craniofacial hyperostosis, Agenesis of corpus callosum, Displacement of the urethral meatus, Brachydactyly, Diaphyseal thickening, Finger syndactyly, Failure to thrive, Facial palsy, Flared metaphysis, Elbow flexion contracture, Delayed skeletal maturation, Limitation of joint mobility, Delayed cranial suture closure, Cleft palate, Thick lower lip vermilion, Microcephaly, Macrocephaly, Symphalangism affecting the phalanges of the hand, Sporadic, Progressive sclerosis of skull base, Prematurely aged appearance, Sparse hair, Proximal symphalangism of hands, Relative macrocephaly, Frontal bossing, Prominent forehead, Scoliosis, Intellectual disability

How does someone get tested for Lenz-Majewski Hyperostotic Dwarfism (LMHD)?

The initial testing for Lenz-Majewski Hyperostotic Dwarfism syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Lenz-Majewski Hyperostotic Dwarfism (LMHD)

This syndrome was probably first described by Braham et al., (1969). It is well reviewed by Gorlin and Whitley (1983). Affected infants have loose, wrinkled skin, prominent veins, especially over the scalp, large floppy ears and failure to thrive. There may be choanal atresia or stenosis and nasolacrimal duct obstruction. Males can have hypospadias and cryptorchidism. The digits are shortened with partial skin syndactyly. Radiographs reveal progressive sclerosis of the skull, facial bones and vertebrae; broad clavicles and ribs; short or absent middle phalanges; diaphyseal under modelling and midshaft cortical thickening; metaphyseal and epiphyseal hyperostosis; and retarded skeletal maturation (Gorlin and Whitley, 1983).
Nishimura et al., (1997) reported a Japanese boy with features of the condition, however, although there was sclerosis of the base of the skull and metaphyseal widening there was no diaphyseal hyperostosis or proximal symphalangism which have been features of previous cases.
Saraiva (2000) reported a female case with dysgenesis of the corpus callosum and a mild hemispheric white matter atrophy. Moderate to severe mental retardation appears to be part of the condition. All cases have been isolated and there is a suggestion of increased parental age.
Majewski (2000) provided a follow up of the original case, at the age of 30 years. The hyperostosis had been progressive and the face became coarse. There was severe mental handicap. A good review of the condition was provided. The case reported by Wattanasirichaigoon et al., (2004) had a cleft palate, facial palsy and a hydrocephalus.
A single case, with mild phenotype, was reported by Dateki et al., (2007). It differed in that there was only diaphyseal under modelling (instead of diaphyseal hyperostosis) and metaepiphyseal sclerosis (instead of metaeiphyseal radiolucency).
Mutations have now been found (Sousa et al., 2014) in PTDSS1 which encodes phosphatidylserine synthetase 1. See also the case reported by Tamhankar et al., (2015) with a mutation.
Piard et al. (2017) described three unrelated individuals with Lenz-Majewski syndrome and a de novo heterozygous mutation in PTDSS1. They presented with cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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