SNP Shot: Genomic Insights

Shprintzen-Goldberg syndrome is a rare disorder impacting multiple body systems. Individuals affected by this syndrome typically exhibit a combination of distinct facial characteristics, along with skeletal and neurological issues.

A frequent finding in individuals with Shprintzen-Goldberg syndrome is craniosynostosis, the premature joining of certain skull bones. This early fusion restricts normal skull growth. Characteristic facial features can include an elongated, narrow head shape; widely spaced eyes (hypertelorism); bulging eyes (exophthalmos); eyes that slant downwards at the outer corners (downslanting palpebral fissures); a high and narrow palate; a small lower jaw (micrognathia); and ears that are set low and rotated backwards.

Individuals with Shprintzen-Goldberg syndrome often have physical characteristics resembling those seen in Marfan syndrome, a related genetic disorder, and are described as having a marfanoid habitus. This can include long, thin fingers (arachnodactyly), unusually long limbs, a chest that caves in (pectus excavatum) or protrudes outwards (pectus carinatum), and an abnormal curvature of the spine (scoliosis). Other skeletal issues may include permanently bent fingers (camptodactyly) and excessive joint flexibility (hypermobility).

Developmental delays and mild to moderate intellectual disability are commonly observed in people with Shprintzen-Goldberg syndrome.

Other typical features of Shprintzen-Goldberg syndrome can involve heart or brain malformations, reduced muscle tone (hypotonia) during infancy, and a soft bulge near the navel (umbilical hernia) or in the lower abdomen (inguinal hernia).

Shprintzen-Goldberg syndrome shares similar signs and symptoms with both Marfan syndrome and another genetic condition called Loeys-Dietz syndrome. However, intellectual disability is more prevalent in Shprintzen-Goldberg syndrome compared to the other two. Moreover, heart problems are more common and often more severe in Marfan syndrome and Loeys-Dietz syndrome.

Inheritance:

Shprintzen-Goldberg syndrome follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene in each cell is enough to cause the condition. In almost all cases, the condition arises from new (de novo) gene mutations, occurring in individuals with no family history of the disorder. Rarely, individuals with Shprintzen-Goldberg syndrome inherit the altered gene from a parent who doesn't show symptoms but carries the mutation in their sperm or egg cells. This situation, where the mutation exists only in reproductive cells, is known as germline mosaicism.