MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Klinické obrazy

7q terminal deletion syndrome

7q35-7q36.3 Deletion - 46,XY,del (7)(q36) 7q terminal deletion syndrome

  • Rare condition presenting with multiple congenital malformations
  • Abnormal brain and facial structures,
  • Developmental delay,
  • Intellectual disability,
  • Abnormal limbs,
  • Sacral anomalies.
  • At least 40 OMIM genes located in the 7q34-7q36.3 region
    • Candidate genes for these phenotypes
  • SHH, EN2, KCNH2, RHEB, HLXB9, EZH2, MNX1 and LIMR1 may be the most important
  • Cca 68 genes, including CNTNAP2, AGAP3, CDK5, CUL1, KMT2C, XRCC2, DPP6, HTR5A, EN2, SHH, LMBR1, KCNH2, PRKAG2, and EZH2

Case of a 2.5-year-old male patient

  • Multiple malformations, congenital brain dysplasia, developmental delay, and intellectual disability.
  • De novo 9.4 Mb deletion in chromosome region 7q35-7q36.3 (chr7:147,493,985–156,774,460) contains 68 genes
  • Brain structure abnormalities
  • Cerebellar sulcus widening in patients with deletion in 7q35-7q36.3.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8671813/

  • Terminal deletions of the long arm of chromosome 7 including 7q35 and/or 7q36 region are well known.
  • Frequently associated with
    • Growth retardation,
    • Microcephaly,
    • Large malformed ears,
    • Cleft lip and palate,
    • Sacral malformations, or agenesis,
    • Holoprosencephaly
      • (involvement of the SHH [OMIM#600725], En2 [OMIM#131310], and HTR5A [OMIM#601305, alias 5-HT5A]) genes located in 7q36.3; Ayub et al., 2016).
      • Report of interstitial deletion that does not implicate the SHH region is missing.
  • Prolonged QT interval
  • onlinelibrary.wiley.com/doi/full/10.1002/mgg3.1645
  • Remarkably high palate.
  • Can affect speech (making it more nasal)
  • Hearing (fluid in the middle ear and glue ear is common)

Currarino syndrome (CS)

  • Peculiar form of caudal regression syndrome
  • Autosomal dominant sacral agenesis (OMIM no. 176450)
  • Partial absence of the sacrum with intact first sacral vertebra
  • Pre-sacral mass
  • Anorectal anomalies (Currarino triad)

3-year-old girl with Currarino triad

  • A de novo 10.3-Mb duplication of 7q34-q35 and an 8.8-Mb deletion on 7q36 identified in this patient
    • Partial sacral agenesis (hemisacrum with remnants of only sacral S1-S2 vertebrae and a residual S3 vertebral body)
    • Associated with complete coccygeal agenesis,
    • Pre-intrasacral dermoid
    • Intra-dural lipoma
    • Ectopic anus
    • Tethered cord
  • Additional systemic features
    • Pre- and post-natal growth impairment (<3rd percentile)
    • Severe microcephaly (<-3 SD) with normal gyration pattern
    • Lack of cortical thickening associated with a hypoplastic inferior vermis
    • Facial dysmorphism,
    • Sensorineural deafness
    • Decreased serum levels of IGF-1
  • HLXB9 homeobox gene (sited between the sonic hedgehog gene and the telomere (tip) of the chromosome)
  • Affects the development of tissues that have their origin in the tail bud of the embryo.
  • Absence can cause a Currarino syndrome
  • A larger 7q36 deletion
    • Other tissues that develop from the embryonic tail bud may also be involved,
      • Anus (the hole for the bottom)
      • Rectum
      • Genital system
      • Urinary tract and the bladder

The most common features

  • Chronic constipation
  • Growth of a cyst
  • Fatty lump or other mass near the sacrum
  • The development of a meningocele
  • A spina bifida-like defect on the inner aspect of the spine
  • Kidney and urinary tract problems
    • Cca 1/3 persons
  • Smaller number develop a bowel obstruction as babies
  • Tethered spinal cord
    • Raises the risk of meningitis
  • Structural defects in the anus and rectum can lead to infections
  • Severity of symptoms varies enormously
  • One third of all people with this syndrome and many Unique members have no obvious signs
  • People with missing sacral bones
    • Remain undiagnosed in the absence of other problems
    • Secondary effects such as severe constipation and urinary tract infections are common
      (Wang 1999; Belloni 2000; Lynch 2000; Horn 2004; U).
  • www.rarechromo.org/media/information/Chromosome%20%207/7q36%20deletions%20FTNW.pdf

Kidneys, bladder and urinary tract

  • Ultrasound scan of the renal system
    • Particularly if they develop a urinary tract infection
  • Kidneys, fistulae (unexpected channels) between the intestines and the urinary system
  • Obstructions or urinary reflux
  • Anomalies that have been found in children with 7q3 deletions include
    • Constrictions of the ureters
    • Urinary tract infections are relatively common
      • Important to be alert (Lurie 1990)
  • In some children the sensation of bladder fullness may be impaired
  • www.rarechromo.org/media/information/Chromosome%20%207/7q36%20deletions%20FTNW.pdf

Constipation

Varlata in 7q36 deletion

Joints

  • Loose and easily dislocatable joints
  • Common feature in children with hypotonia (floppy muscles)
  • Almost half of Unique 7q36 deletion families
  • Hips, shoulders, ankles, elbows and fingers
  • Some children with flexible ankle joints have needed orthotic supports (DAFOs)
    • Reported an improvement with time
  • Most children have not needed any special treatment or surgery
  • www.rarechromo.org/media/information/Chromosome%20%207/7q36%20deletions%20FTNW.pdf

Srdce

  • Around one person in five with a 7q36 deletion
    • Heart problem inborned
  • Ventricular septal defects (VSDs, holes between the pumping chambers of the heart)
  • Anomalies of the blood vessels leading to and from the heart
  • VSD
  • Double outlet right ventricle
  • Cyst on the left ventricle
  • Small holes may well close up naturally in time (Tiller 1988;U)
  • www.rarechromo.org/media/information/Chromosome%20%207/7q36%20deletions%20FTNW.pdf

Squint (strabismus)

Long sight

Structural anomalies of the eye

  • Congenital blindness in a child with 7q34qter
    • Optic nerve coloboma
    • Severe microphthalmus
    • Large retinal coloboma
(Taysi 1982; Reynolds 1984)

Holoprosencephaly

  • Syndromic holoprosencephaly due to the involvement of
    • SHH (aliases HHG1, SMMCI, TPT, TPTPS, and MCOPCB5) gene region
    • Interstitial deletions including CNTNAP2 (aliases Caspr2, KIAA0868, and NRXN4)
    • Excluding the SHH region
  • The common clinical features were
    • Abnormal maternal serum screening during first-trimester pregnancy
    • Low occipitofrontal circumference at birth,
    • Hypotonia, abnormal feet,
    • Developmental delay,
    • Impaired language development,
    • Generalized seizures,
    • Hyperactive behavior,
    • Friendly personality,
    • Cranio-facial dysmorphism
  • onlinelibrary.wiley.com/doi/full/10.1002/mgg3.1645
  • The absence of the so-called Sonic Hedgehog (SHH) gene at 7q36
  • Associated with holoprosencephaly - HPE
  • From being scarcely noticeable to very severe

Mild form of HPE might show as a single central front tooth

  • Other abnormalities of the teeth in the upper jaw
  • Extremely small head (microcephaly)
  • Close set eyes
  • Narrow nasal and throat passages
  • Cleft palate
  • Absence of the sense of smell

Most severe form

  • Brain fails to develop into two halves (hemispheres)
    • Serious effects on its function
  • Many children with HPE associated with a terminal 7q deletion only show minimal signs
    • Most characteristically microcephaly (Benzacken 1997; Horn 2004; U).

SHH gene is missing


GPT January 2022, specific metabolic pathways affected by the deletion in 7q35-36.3

  • Insulin-Like Growth Factor (IGF) Pathway:
    • IGF pathway deficit - role in growth and development.
  • Catecholamine Metabolism:
    • Synthesis or regulation of catecholamines, such as dopamine, norepinephrine, and epinephrine.
  • Amino Acid Metabolism:
    • May be implications for amino acid metabolism.
  • Cholesterol Metabolism:
  • Glycolysis and Gluconeogenesis:
    • Might be involved in glucose metabolism.

V.s. predispozice k některým typům Ca a horší prognóze

  • In myeloid disorders, monosomy 7 or del(7q)
    • Most common recurrent chromosome abnormalities
    • In 8% of de novo acute myeloid leukemia (AML)
    • In 5-10% of de novo patients with myelodysplastic syndrome (MDS)
    • In approximately 50% of therapy-related myeloid neoplasms
  • Myeloid malignancies with monosomy 7 or del(7q)
    • Respond poorly to chemotherapy
    • Associated with an unfavorable prognosis
    • 7/del(7q) contribute to leukemic growth in myeloid malignancies
  • Several commonly deleted regions (CDRs)located on 7q identified in MDS and AML:
    • 7q22,
    • 7q32-33,
    • 7q35-36

7q22

  • CUX1
    • Transcription factor encoded at 7q22 - tumor suppressor activity
    • Loss of CUX1 may thus contribute to disease pathogenesis

7q35-36

  • Encodes nine genes including CUL1 and EZH2
    • The most promising candidates due to known function in and association with cancer
www.biotrend.com/en/buy/cat-cux1-probe-for-fish-ce-ivd-acute-4618.html



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Poslední aktualizace: 30. 11. 2023 1:39:10