Stromme Syndrome (STROMS) – 48 Symptoms and signs, Interesting Facts, Prognosis

Reviewed by Dr Shakthi

What is Stromme Syndrome (STROMS)

Stromme Syndrome is a rare congenital disease.

This Syndrome is an autosomal recessive congenital disorder which affects multiple organ systems

This affect on the multiple organ systems in the body results in various clinical symptoms and signs.

The onset of Stromme Syndrome is in utero
Early childhood lethality may occur
STROMS is a highly variable phenotype

Synonyms

  1. Jejunal Atresia with Microcephaly and ocular anomalies
  2. Apple Peel Syndrome with Microcephaly and ocular anomalies
  3. Ciliary Dyskinesia, Primary, 31, Formerly
  4. CILD31, Formerly
  5. Apple-peel intestinal atresia-ocular anomalies-microcephaly syndrome
  6. Jejunal atresia-microcephaly-ocular anomalies syndrome

Prevalence of Stromme Syndrome

This condition affects less than 1 in 1000000

Till date, Stromme Syndrome was identified in a couple of siblings and also 7 additional sporadic patients

What causes Stromme Syndrome?

The exact cause of Stromme Syndrome is unknown till date.

STROMS is caused by a mutation called as compound heterozygous mutation (a mutation is a change or alteration in the DNA sequence due to several reasons) in the CENPF (centromere protein F) gene on the chromosome 1q41.

Age of onset of STROMS

  • Antenatal

Inheritance

  • The Stromme Syndrome is Autosomal recessive

Symptoms of Stromme Syndrome

Symptoms – affecting head

  • 1. Microcephaly – a condition where the circumference of the head is smaller than the normal size.
  • 2. Hydrocephalus – This is a condition characterised by an accumulation of a fluid in the brain cavities called cerebrospinal fluid (CSF).

Symptoms – affecting face

  • 3. Micrognathia – it is a disorder in which the lower jaw is very small than the normal size
  • 4. Sloped forehead
  • 5. A Skin tag on the left cheek
  • 6. Long philtrum
  • 7. Metopic suture synostosis – this is a condition characterised by premature fusion of a suture called metopic suture in the middle of the forehead.

Symptoms – affecting eyes

  • 8. Microphthalmia – a condition in which an eye ball is missing, or one or both eyeballs will be abnormally small in size
  • 9. Microcornea – this is an condition in which the cornea of the eye is abnormally small in size, roughly less than 10 mm in diameter.
  • 10. Anterior chamber abnormalities
  • 11. Sclerocornea – this is a condition in which there is no demarcated boundary between cornea and sclera parts of the eye, which results in opacity leading to blurred vision. This disorder is congenital.
  • 12. Iris coloboma – this disorder is characterised by a key hole in iris, which is a part of the eye, typically, iris coloboma do not cause vision loss.
  • 13. Optic nerve hypoplasia – this is a congenital disease characterised by under developed optic nerves, these are the crucial nerves in the eye.
  • 14. Peters anomaly – this is a disorder due to a group of diseases resulting in opacity of the important part of the eye called cornea leading to decreased vision. This is seen at birth.
  • 15. Tortuous retinal vessels – the blood vessels of retina part of the eye becomes tortuous
  • 16. Cataracts
  • 17. Hypertelorism 
  • 18. Deep set eyes 
  • 19. Peripheral anterior synechia – this is a condition due to adhesions of two structures in the eye, peripheral iris and angle of anterior chamber.
  • 20. Left sectoral iris stromal hypoplasia
  • 21. Corectopia – this is a disorder characterised by the displacement of the pupil part of the eye from its original central position. It may be related to high myopia.
  • 22. Mild left blepharoptosis – blepharoptosis is a condition characterised by low lying position of upper eyelid margin with eye always in primary gaze.

Symptoms – affecting ears

  • 23. Low set ears
  • 24. Large ears

Symptoms – affecting nose

  • 25. Broad nasal bridge 
  • 26. High nasal bridge 
  • 27. Short columella

Symptoms – affecting mouth

  • 28. Wide mouth 
  • 29. Cleft palate – This is a congenital disorder characterised by a split or opening in the roof of the mouth which happens when the tissues doesn’t fuse together at the time of development in the womb. Cleft palate usually associated with a cleft lip that is the split in the upper lip but it is not a rule, this can occur without affecting the lip as well.

Symptoms – affecting heart

  • 30. Persistent foramen ovaleThis condition is a patent hole in the heart which is called foramen ovale, which is supposed to close before birth.
  • 31. Myopathic changes
  • 32. Hypoplastic muscular tissue – The muscles of the heart abnormally smaller than the usual size.
  • 33. Small cardiomyocytes with little cytoplasm
  • 34. Secundum atrial septal defect – This disorder causes shunting of blood between systemic and pulmonary circulations. This defect is congenital disorder.

Symptoms – affecting abdomen

  • 35. Accessory spleen – This condition is characterised by extra splenic tissue apart from the main splenic structure.
  • 36. Duodenal atresia – This disease is the complete absence or the duodenal lumen, sometimes complete closure of a portion of the lumen. This is a birth defect.
  • 37. Jejunal atresia – This condition is characterised by complete or partial absence of mesentery (which is a connecting membrane from the small intestines to the abdominal wall). It is a congenital disease.
  • 38. Intestinal atresia – This is a disorder due to complete obstruction and blockage in any part of the intestines.
  • 39. Intestinal malrotation – This is a condition which usually happens in the early pregnancy, the intestines of the baby twist which leads to blockage.

Symptoms – affecting kidneys

  • 40. Renal hypodysplasia – This is a congenital disorder characterised by small kidneys with reduced number of units of kidney callled nephrons.
  • 41. Hydronephrosis – This condition is due to swelling of one or both kidneys.

Symptoms – affecting hands

  • 42. Preaxial Polydactyly – Extra digit towards the first digit of the hand.
  • 43. Hypertonia in few children – Hypertonia is the excessive tone of the muscle but reduced capacity of the muscle to stretch.

Symptoms – affecting brain

  • 44. Learning disabilities
  • 45. Agenesis of the corpus callosum – Agenesis of the corpus callosum is a congenital disease with characteristic features of partial or complete absence of an important structure in the brain known as corpus callosum.
  • 46. Cerebellar hypoplasia – Cerebellar hypoplasia is a condition resulting from the underdeveloped cerebellum. Cerebellum is an important structure of the brain. There are situations wherein this structure cerebellum could be very small.
  • 47. Mild developmental delays

Symptoms – affecting Lungs

  • 48. Aberrant right tracheobronchial tree

New Symptoms of Stromme Syndrome

A patient had the below additional features

  • Edema of lower extremities – edema in lower extremities was detected prenatally and was also seen at the birth in patient. Albumin level was normal.
  • Renal parenchymal changes
  • Thrombocytopenia
  • Cardiac anomaly

What Research says about Stromme Syndrome

Study 1 – A case report of a young man who has been followed since he was born in 2000; in his first days of life, he needed abdominal surgery due to an intestinal apple peel-type atresia

This young adult with a genetic diagnosis of Stromme syndrome who—in addition to classic microcephalia, microphthalmia and intestinal atresia (apple peel-type)—experienced slow and unexpected evolution to end-stage renal disease (ESRD).

This study underlines the need to perform renal follow-up in these patients.

CENPF variants can cause kidney malformations, as has been previously shown in the literature and this unique case with evolution to end-stage renal disease during the second decade of life.

Study 2 – Slee and Goldblatt (1996) reported a 5 year old boy with microcephaly, anterior segment abnormalities, a rudimentary iris, apple peel deformity with jejunal atresia, Meckel diverticulum and developmental delay. Short stature and hydrocephalus developed.


Study 3 – Bellini et al., (2002) reported a further case with this association. MRI and CT brain scans showed a normal, small brain. There were no ocular abnormalities.


Study 4 – Bower et al., (2003) report a case with this association where mosaic variegated aneuploidy was demonstrated on cytogenetic analysis. The authors emphasise the importance of an extended chromosome type where this condition is expected.

When was Stromme Syndrome first identified?

In the year 1993, Norwegian paediatrician Petter Stromme and his associates at Rogaland Central Hospital, Norway first identified this condition, Stromme Syndrome

This is detected in two infant siblings presented with “apple peel” type intestinal atresia, abnormalities in the eye (ocular anomalies) and microcephaly.

This was proposed as a new syndrome.

After few years, further research by Slee and Goldblatt (1996),Shanske et al. (2002), Bellini et al. (2002) and others conducted studies on other patients presenting with similar symptoms.

In 2008, Van Bever et al. proposed that the syndrome to be named after Strømme, this was after encountering another patient who seemed to have the syndrome.

A genetic analysis was conducted in 2015 by Waters et al. on a British family in whom four foetuses had miscarried with symptoms of a ciliopathy. Mutations were identified in the foetuses in both copies of CENPF.

Subsequently a cohort of 1,000 individuals were ancrocephaly and found that one of them, a girl, had mutations in both of her copies of CENPF.

Her learning delay was mild-to-moderate, and she did not have any other issues with her bodily systems. This confirmed that mutations in CENPF are pathogenic for the first time.

In 2016, Filges et al. followed up with Strømme’s original two siblings and found using whole exome sequencing that they both had mutations in both of their copies of CENPF, establishing mutations in CENPF as the cause of Strømme syndrome.

How is this condition diagnosed?

The diagnosis of Stromme syndrome a CENPF related disorder has important implications for management.

  • MRI Brain which might show lissencephaly
  • High resolution karyotyping
  • TORCH studies
  • Renal and cardiac ultrasound examinations
  • CT Brain

Prognosis

  • The prognosis is highly variable.
  • The prognosis is largely dependent on the presence of the type of malformations in the individual patient, most importantly if there are any associated brain abnormalities or malformations.
  • Among two adults presenting with Stromme syndrome, both of them have survived surgery of intestinal atresia which has been done early. A long term follow up has been done for both of them. They are happily living independently.
  • On the worst case scenario, adverse outcomes which might include fetal and neonatal lethality must be considered.
  • Cognitive impairment may be associated in varying degrees ranging from learning difficulties to intellectual disability.

Stromme Syndrome Life Expectancy

Usually the children affected with Stromme Syndrome have very low Life Expectancy

The quality of life in these children is minimum due to the complications arising from this Syndrome

Does the result of a genetic test resolve the genetic situation in that family?

Yes. If compound heterozygous or homozygous variants affecting function are identified in the index patient, carrier testing can be offered to other family members as appropriate.

Reproductive options such as prenatal diagnosis or preimplantation genetic diagnosis can be offered to carrier parents.

Does Stromme Syndrome cause kidney damage?

A study of a young adult who presented with a genetic diagnosis of Stromme syndrome, apart from classic microcephalia, microphthalmia and apple peel-type intestinal atresia experienced slow and unexpected evolution to end-stage renal disease (ESRD)

From the research till date, out of total 11 individuals with LoF CENPF variants, six of which died in utero and presented a classical Stromme phenotype associated with bilateral kidney hypoplasia 

How is this condition treated?

  • As on date, there are no specific causal therapies for STROMS
  • Potentially life saving surgical treatment like Intestinal surgery are options.
  • Ophthalmologic and neurodevelopmental interventions are promising.
  • Intestinal surgery is life-saving and is successful
  • Right time diagnosis must prompt ophthalmological and neurodevelopmental evaluation in a child with stromme syndrome.
  • Early interventions always improves the long term outcome of the child affected with STROMS.
  • Early prenatal diagnosis and/or preimplantation genetic diagnosis will be a favourable option for excellent prognosis.

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