Lamb-Shaffer syndrome is a rare autosomal dominant condition.
[Lamb AN, Rosenfeld JA, Neill NJ, Talkowski ME, Blumenthal I, Girirajan S., Keelean-Fuller D, Fan Z, Pouncey J, Stevens, C., Mackay-Loder L, Terespolsky D, and 31 others. Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features. Hum Mutat 33: 728-740] Less than 40 cases have been reported by 2018.
Signs and symptoms
Clinical features include
[Nesbitt A, Bhoj EJ, McDonald Gibson K, Yu Z, Denenberg E, Sarmady M, Tischler T, Cao K, Dubbs H, Zackai EH, Santani A (2015) Exome sequencing expands the mechanism of SOX5-associated intellectual disability: a case presentation with review of SOX-related disorders. Am J Med Genet 167A: 2548-2554]
* Global developmental delay
* Significant speech delay
*
Hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...
*
Micrognathia
Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...
*
Scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
* Defects in motor function both fine and gross
*
Optic atrophy Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain.
Damage and death of these nerve cells, or neurons, leads to characteristic featu ...
* Ocular motor apraxia
*
Strabismus
Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...
* Frontal bossing
* Ear abnormalities
* Low nasal bridge
* Epicanthal folds
* Midline tongue groove
Genetics
This condition is caused by mutations in the SRY-related HMG-box (
SOX5
Transcription factor SOX-5 is a protein that in humans is encoded by the ''SOX5'' gene.
Function
This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development an ...
) gene.
[Lee RWY, Bodurtha J, Cohen J, Fatemi A, Batista D (2013) Deletion 12p12 involving SOX5 in two children with developmental delay and dysmorphic features. Pediat Neurol 48: 317-320] This gene encodes a protein in the family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate.
The gene is located on the short arm of
chromosome 12
Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...
(12p12).
A study published in 2019 examining 34 families shows that 74% (25/34 families) of the condition are likely to be of
de novo occurrence as the variants could not be detected in parental blood samples. In 15% (5/34 families) of the patients the condition was likely inherited from a mosaic parent. In 3% (1/34), the condition was inherited from an affected parent.
This means that the majority of the patients have parents who are unaffected whereas inheritance is also possible.
Pathogenesis
How this mutation causes the clinical picture is not currently clear.
Diagnosis
The diagnosis may be suspected on the basis of the constellation of clinical features but may only be determined by a genetic test. The full exome sequencing test is used to determine the partial deletion, deletion,or mutation to the SOX5 gene. It is made by sequencing the SOX5 gene responsible for the cells that facilitate information transferring in the brain. Symptoms of Lamb-Shaffer syndrome include fine and gross motor delays, speech delay, global developmental delay,hypotonia and issues with vision, commonly misdiagnosed for autism.
Treatment
There is currently no curative treatment for this condition. Supportive management is all that is currently available.
Epidemiology
This is a rare condition with a prevalence of < 1/10
6. The total number of cases reported to date is <40.
History
This condition was first described by Lamb ''et al'' in 2012
[Lamb AN, Rosenfeld JA, Neill NJ, Talkowski ME, Blumenthal I, Girirajan S., Keelean-Fuller D, Fan Z, Pouncey J, Stevens, C., Mackay-Loder L, Terespolsky D, and 31 others. Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features. Hum Mutat 33: 728-740]
References
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Genetic diseases and disorders
Rare diseases