Shprintzen-Goldberg syndrome

Shprintzen-Goldberg syndrome, often shortened to SGS, is a rare connective tissue disorder that affects the shape of the face and skull, skeletal development and the cardiovascular system. NORD describes it as extremely rare, with fewer than 50 patients documented in the medical literature as of 2024.

The SKI gene normally helps regulate cell growth. In SGS, a pathogenic variant changes how SKI works, and the condition follows an autosomal dominant pattern, meaning one altered copy is enough. NORD explains that most cases occur spontaneously as de novo changes, so parents typically do not carry the variant themselves.

NORD lists premature fusion of skull bones in infancy, called craniosynostosis, widely spaced eyes, distinctive facial features and intellectual disability. Other characteristics include long fingers, flat feet, low muscle tone and potential heart valve problems.

The skeletal build can give a Marfan-like appearance, with long limbs and fingers. NORD notes that SGS is often misdiagnosed as Marfan syndrome, which is why a child who has both a Marfan-like body shape and early skull fusion or developmental delay is usually referred for a broader genetic assessment.

• Head and face: early skull fusion, widely spaced eyes and distinctive facial features.

• Skeleton: long fingers, flat feet and a tendency to spinal curvature.

• Muscles and development: low muscle tone and intellectual disability.

• Heart: valve problems and the need for aortic surveillance.

NORD states that diagnosis relies on finding a pathogenic SKI variant through genetic testing, combined with a clinical examination of the characteristic features. In the UK, a clinical geneticist usually arranges testing, often as part of a panel of genes linked to connective tissue and skull-shape disorders.

A result guides surveillance and also tells the family that the condition is most likely a new change, though germline mosaicism, in which a parent carries the variant in some egg or sperm cells, cannot always be excluded, so genetic counselling for parents is advised.

NORD describes care through a multidisciplinary team, with regular cardiac monitoring using echocardiograms, annual spine imaging to detect changes, and surgery when needed for skeletal or craniofacial abnormalities. Craniosynostosis is usually assessed by a craniofacial or neurosurgical team, because early fusion can limit the room for the brain to grow.

Developmental support is central. Early intervention services, speech and language therapy, physiotherapy to address low muscle tone, and educational support tailored to the child's needs all contribute. Eye, hearing and dental reviews are routine in rare syndromes of this type.

Marfan syndrome arises from FBN1 and Loeys-Dietz syndrome from genes in the TGF-beta signalling pathway, while SGS arises from SKI. Craniosynostosis and intellectual disability are more characteristic of SGS than of Marfan syndrome, in which learning is typically unaffected. Lens dislocation is a classic Marfan finding that is not the leading feature of SGS.

Distinguishing between them matters because the surveillance plan, the genetic counselling and the long-term outlook differ. Loeys-Dietz syndrome, in particular, has its own recommendations on aortic imaging and surgery thresholds that are set by specialist centres.

Because so few people have been described, long-term outcome data are limited and individual outlook depends mostly on the heart findings, the spine and the level of developmental support. Specialist teams plan reviews through childhood and into the move to adult services.

Seek prompt advice for any rapid change in head shape, vomiting with drowsiness or persistent headache in a child with craniosynostosis, new weakness, back pain or breathing difficulty. Sudden severe chest or back pain, fainting or collapse needs 999, and people carrying a letter that names the diagnosis help emergency teams respond quickly.