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Holoprosencephaly-radial heart renal anomalies syndrome

MedGen UID:
401047
Concept ID:
C1866649
Disease or Syndrome
Synonym: Steinfeld syndrome
SNOMED CT: Steinfeld syndrome (716233007)
 
Monarch Initiative: MONDO:0008488
OMIM®: 184705
Orphanet: ORPHA3186

Definition

This syndrome has characteristics of holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder. It has been described in two families (with at least seven affected persons). Variable manifestations include vertebral anomalies, cleft lip/palate, microphthalmia, absent nose, dysplastic ears, hearing loss, colobomas of the iris and retina and/or bifid uvula. Inheritance is likely to be autosomal dominant with variable expressivity. [from SNOMEDCT_US]

Clinical features

From HPO
Unilateral renal dysplasia
MedGen UID:
140916
Concept ID:
C0431697
Congenital Abnormality
A unilateral form of developmental dysplasia of the kidney.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
Underdevelopment of the radius.
Hypoplasia of the ulna
MedGen UID:
395934
Concept ID:
C1860614
Congenital Abnormality
Underdevelopment of the ulna.
Aplasia/Hypoplasia of the thumb
MedGen UID:
465975
Concept ID:
C3179508
Finding
Hypoplastic/small or absent thumb.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Congenital Abnormality
Any structural anomaly of the heart and blood vessels.
Isolated agenesis of gallbladder
MedGen UID:
82736
Concept ID:
C0266251
Congenital Abnormality
A developmental defect in which the gallbladder fails to form.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Holoprosencephaly sequence
MedGen UID:
38214
Concept ID:
C0079541
Congenital Abnormality
Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.\n\nNonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms.\n\nPeople with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia).\n\nSome individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member.\n\nMost people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing.
Phocomelia
MedGen UID:
10721
Concept ID:
C0031575
Congenital Abnormality
Missing or malformed long bones of the extremities with the distal parts (such as hands and/or feet) connected to the variably shortened or even absent extremity, leading to a flipper-like appearance, as opposed to other forms of limb malformations were either the hole limb is missing (such as amelia), or the distal part of a limb is absent (peromelia).
Missing ribs
MedGen UID:
98093
Concept ID:
C0426816
Finding
A developmental anomaly with absence of one or more ribs.
Abnormal vertebral morphology
MedGen UID:
371742
Concept ID:
C1834129
Anatomical Abnormality
An abnormality of one or more of the vertebrae.
Abnormality of the vertebral column
MedGen UID:
892426
Concept ID:
C4021789
Anatomical Abnormality
Any abnormality of the vertebral column.
Aplasia of the nose
MedGen UID:
120555
Concept ID:
C0265740
Congenital Abnormality
Complete absence of all nasal structures.
Median cleft upper lip
MedGen UID:
342454
Concept ID:
C1850256
Congenital Abnormality
A type of cleft lip presenting as a midline (median) gap in the upper lip.
Median cleft palate
MedGen UID:
340670
Concept ID:
C1850968
Congenital Abnormality
Cleft palate of the midline of the palate.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Iris coloboma
MedGen UID:
116097
Concept ID:
C0240063
Anatomical Abnormality
A coloboma of the iris.
Retinal coloboma
MedGen UID:
761889
Concept ID:
C3540764
Disease or Syndrome
A notch or cleft of the retina.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHoloprosencephaly-radial heart renal anomalies syndrome
Follow this link to review classifications for Holoprosencephaly-radial heart renal anomalies syndrome in Orphanet.

Professional guidelines

PubMed

Adams D, Ando Y, Beirão JM, Coelho T, Gertz MA, Gillmore JD, Hawkins PN, Lousada I, Suhr OB, Merlini G
J Neurol 2021 Jun;268(6):2109-2122. Epub 2020 Jan 6 doi: 10.1007/s00415-019-09688-0. PMID: 31907599Free PMC Article
Lagan N, Huggard D, Mc Grane F, Leahy TR, Franklin O, Roche E, Webb D, O' Marcaigh A, Cox D, El-Khuffash A, Greally P, Balfe J, Molloy EJ
Acta Paediatr 2020 Jun;109(6):1096-1111. Epub 2020 Jan 24 doi: 10.1111/apa.15153. PMID: 31899550
Morgan T
Am Fam Physician 2007 Aug 1;76(3):405-10. PMID: 17708142

Recent clinical studies

Etiology

Lagan N, Huggard D, Mc Grane F, Leahy TR, Franklin O, Roche E, Webb D, O' Marcaigh A, Cox D, El-Khuffash A, Greally P, Balfe J, Molloy EJ
Acta Paediatr 2020 Jun;109(6):1096-1111. Epub 2020 Jan 24 doi: 10.1111/apa.15153. PMID: 31899550
Deeks SG, Overbaugh J, Phillips A, Buchbinder S
Nat Rev Dis Primers 2015 Oct 1;1:15035. doi: 10.1038/nrdp.2015.35. PMID: 27188527
Roberts AE, Allanson JE, Tartaglia M, Gelb BD
Lancet 2013 Jan 26;381(9863):333-42. Epub 2013 Jan 10 doi: 10.1016/S0140-6736(12)61023-X. PMID: 23312968Free PMC Article
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R
J Am Coll Cardiol 2008 Nov 4;52(19):1527-39. doi: 10.1016/j.jacc.2008.07.051. PMID: 19007588
Morgan T
Am Fam Physician 2007 Aug 1;76(3):405-10. PMID: 17708142

Diagnosis

McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS
Nat Rev Dis Primers 2015 Nov 19;1:15071. doi: 10.1038/nrdp.2015.71. PMID: 27189754Free PMC Article
Roberts AE, Allanson JE, Tartaglia M, Gelb BD
Lancet 2013 Jan 26;381(9863):333-42. Epub 2013 Jan 10 doi: 10.1016/S0140-6736(12)61023-X. PMID: 23312968Free PMC Article
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R
J Am Coll Cardiol 2008 Nov 4;52(19):1527-39. doi: 10.1016/j.jacc.2008.07.051. PMID: 19007588
Morgan T
Am Fam Physician 2007 Aug 1;76(3):405-10. PMID: 17708142

Therapy

Düsing P, Zietzer A, Goody PR, Hosen MR, Kurts C, Nickenig G, Jansen F
J Mol Med (Berl) 2021 Mar;99(3):335-348. Epub 2021 Jan 22 doi: 10.1007/s00109-021-02037-7. PMID: 33481059Free PMC Article
Costanzo MR
Heart Fail Clin 2020 Jan;16(1):81-97. doi: 10.1016/j.hfc.2019.08.010. PMID: 31735318
Deeks SG, Overbaugh J, Phillips A, Buchbinder S
Nat Rev Dis Primers 2015 Oct 1;1:15035. doi: 10.1038/nrdp.2015.35. PMID: 27188527
Sica DA, Carter B, Cushman W, Hamm L
J Clin Hypertens (Greenwich) 2011 Sep;13(9):639-43. Epub 2011 Jul 27 doi: 10.1111/j.1751-7176.2011.00512.x. PMID: 21896142Free PMC Article
Morgan T
Am Fam Physician 2007 Aug 1;76(3):405-10. PMID: 17708142

Prognosis

Koratala A, Verbrugge F, Kazory A
Adv Kidney Dis Health 2024 Mar;31(2):127-132. doi: 10.1053/j.akdh.2023.07.002. PMID: 38649216
Rocha EA, Mehta N, Távora-Mehta MZP, Roncari CF, Cidrão AAL, Elias Neto J
Arq Bras Cardiol 2021 Apr;116(4):814-835. doi: 10.36660/abc.20200420. PMID: 33886735Free PMC Article
Roberts AE, Allanson JE, Tartaglia M, Gelb BD
Lancet 2013 Jan 26;381(9863):333-42. Epub 2013 Jan 10 doi: 10.1016/S0140-6736(12)61023-X. PMID: 23312968Free PMC Article
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R
J Am Coll Cardiol 2008 Nov 4;52(19):1527-39. doi: 10.1016/j.jacc.2008.07.051. PMID: 19007588

Clinical prediction guides

Koratala A, Verbrugge F, Kazory A
Adv Kidney Dis Health 2024 Mar;31(2):127-132. doi: 10.1053/j.akdh.2023.07.002. PMID: 38649216
Evenepoel P, Stenvinkel P, Shanahan C, Pacifici R
Nat Rev Nephrol 2023 Oct;19(10):646-657. Epub 2023 Jul 24 doi: 10.1038/s41581-023-00736-7. PMID: 37488276
Yoon SH, Kim GY, Choi GT, Do JT
Cells 2023 May 11;12(10) doi: 10.3390/cells12101365. PMID: 37408200Free PMC Article
Thakur S, Chaddha V, Gupta R, Singh C, Dagar S, Shastri A, Tiwari B, Kavitha, Sethia V, Malik M, Jain P, Kapoor A, Kapoor A, Kapoor T, Kapoor A, Kapoor R, Kumar M, Uppal R
J Clin Ultrasound 2023 Jan;51(1):96-106. Epub 2022 Aug 10 doi: 10.1002/jcu.23273. PMID: 36639848
Patel KP, Katsurada K, Zheng H
Circ Res 2022 May 13;130(10):1601-1617. Epub 2022 May 12 doi: 10.1161/CIRCRESAHA.122.319989. PMID: 35549375Free PMC Article

Recent systematic reviews

Patti G, Scaglione M, Maiorano NG, Rosti G, Divizia MT, Camia T, De Rose EL, Zucconi A, Casalini E, Napoli F, Di Iorgi N, Maghnie M
Front Endocrinol (Lausanne) 2023;14:1213098. Epub 2023 Jul 28 doi: 10.3389/fendo.2023.1213098. PMID: 37576960Free PMC Article
Ghauri H, Iqbal R, Ahmed S, Ashraf A, Khan MSQ, Malik J, Zaidi SMJ, Almas T
Pacing Clin Electrophysiol 2022 May;45(5):681-687. Epub 2022 Apr 9 doi: 10.1111/pace.14484. PMID: 35304920
León NY, Harley VR
Hum Genet 2021 Dec;140(12):1625-1634. Epub 2021 Sep 15 doi: 10.1007/s00439-021-02361-5. PMID: 34524523
Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R, Berl T, Bobek I, Cruz DN, Daliento L, Davenport A, Haapio M, Hillege H, House AA, Katz N, Maisel A, Mankad S, Zanco P, Mebazaa A, Palazzuoli A, Ronco F, Shaw A, Sheinfeld G, Soni S, Vescovo G, Zamperetti N, Ponikowski P; Acute Dialysis Quality Initiative (ADQI) consensus group
Eur Heart J 2010 Mar;31(6):703-11. Epub 2009 Dec 25 doi: 10.1093/eurheartj/ehp507. PMID: 20037146Free PMC Article

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