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Feingold syndrome type 1(FGLDS1)

MedGen UID:
1637716
Concept ID:
C4551774
Disease or Syndrome
Synonyms: Digital anomalies with short palpebral fissures and atresia of esophagus, or duodenum; FGLDS1; MICROCEPHALY AND DIGITAL ABNORMALITIES WITH NORMAL INTELLIGENCE; MICROCEPHALY, MENTAL RETARDATION, AND TRACHEOESOPHAGEAL FISTULA SYNDROME; Microcephaly-oculo-digito-esophageal-duodenal syndrome; Oculodigitoesophagoduodenal syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): MYCN (2p24.3)
 
Monarch Initiative: MONDO:0008115
OMIM®: 164280
Orphanet: ORPHA391641

Disease characteristics

Excerpted from the GeneReview: Feingold Syndrome 1
Feingold syndrome 1 (referred to as FS1 in this GeneReview) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild-to-moderate learning disability. [from GeneReviews]
Authors:
Carlo LM Marcelis  |  Arjan PM de Brouwer   view full author information

Additional descriptions

From OMIM
Feingold syndrome is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disability/mental retardation. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients (summary by Teszas et al., 2006). Genetic Heterogeneity of Feingold Syndrome Feingold syndrome-2 (FGLDS2; 614326) is caused by hemizygous deletion of the MIR17HG gene (609415) on chromosome 13q31.3.  http://www.omim.org/entry/164280
From MedlinePlus Genetics
Individuals with Feingold syndrome type 1 or type 2 have characteristic abnormalities of their fingers and toes. Almost all people with this condition have a specific hand abnormality called brachymesophalangy, which refers to shortening of the second and fifth fingers. Other common abnormalities include fifth fingers that curve inward (clinodactyly), underdeveloped thumbs (thumb hypoplasia), and fusion (syndactyly) of the second and third toes or the fourth and fifth toes.

Additional common features of both types of Feingold syndrome include an unusually small head size (microcephaly), a small jaw (micrognathia), a narrow opening of the eyelids (short palpebral fissures), and mild to moderate learning disabilities. Less often, affected individuals have hearing loss, short stature, or kidney or heart abnormalities.

People with Feingold syndrome type 1 are frequently born with a blockage in part of their digestive system called gastrointestinal atresia. In most cases, the blockage occurs in the esophagus (esophageal atresia) or in part of the small intestine (duodenal atresia). Individuals with type 2 do not have gastrointestinal atresias.

Feingold syndrome is a disorder that affects many parts of the body. There are two types of Feingold syndrome, distinguished by their genetic cause; both types have similar features that can vary among affected individuals.  https://medlineplus.gov/genetics/condition/feingold-syndrome

Clinical features

From HPO
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Short toe
MedGen UID:
322858
Concept ID:
C1836195
Finding
A toe that appears disproportionately short compared to the foot.
4-5 toe syndactyly
MedGen UID:
324891
Concept ID:
C1837836
Finding
Syndactyly with fusion of toes four and five.
Short middle phalanx of finger
MedGen UID:
337690
Concept ID:
C1846950
Finding
Short (hypoplastic) middle phalanx of finger, affecting one or more fingers.
2-3 toe syndactyly
MedGen UID:
1645640
Concept ID:
C4551570
Congenital Abnormality
Syndactyly with fusion of toes two and three.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Tricuspid stenosis
MedGen UID:
21678
Concept ID:
C0040963
Disease or Syndrome
A narrowing of the orifice of the tricuspid valve of the heart.
Aortic arch interruption
MedGen UID:
57773
Concept ID:
C0152419
Congenital Abnormality
Non-continuity of the arch of aorta with an atretic point or absent segment.
Tricuspid atresia
MedGen UID:
67034
Concept ID:
C0243002
Congenital Abnormality
Failure to develop of the tricuspid valve and thus lack of the normal connection between the right atrium and the right ventricle.
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A developmental defect resulting in complete obliteration of the lumen of the esophagus such that the esophagus ends in a blind pouch rather than connecting to the stomach.
Annular pancreas
MedGen UID:
56211
Concept ID:
C0149955
Congenital Abnormality
A congenital anomaly in which the pancreas completely (or sometimes incompletely) encircles the second portion of duodenum and occasionally obstructs the more proximal duodenum.
Duodenal atresia
MedGen UID:
75602
Concept ID:
C0266174
Congenital Abnormality
A developmental defect resulting in complete obliteration of the duodenal lumen, that is, an abnormal closure of the duodenum.
Jejunal atresia
MedGen UID:
75603
Concept ID:
C0266175
Congenital Abnormality
Jejunal atresia is the most common cause of bowel obstruction in the newborn. In this condition, because of agenesis of the mesentery, the distal small bowel comes straight off the caecum and twists around the marginal artery, suggesting a maypole, a Christmas tree, or an apple peel at operation. Obliteration of the superior mesenteric artery may underlie this malformation.
Gastrointestinal atresia
MedGen UID:
871218
Concept ID:
C4025697
Disease or Syndrome
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Prominent occiput
MedGen UID:
381255
Concept ID:
C1853737
Finding
Increased convexity of the occiput (posterior part of the skull).
Small anterior fontanelle
MedGen UID:
347886
Concept ID:
C1859455
Finding
Abnormally decreased size of the anterior fontanelle with respect to age-dependent norms.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Tracheoesophageal fistula
MedGen UID:
21228
Concept ID:
C0040588
Anatomical Abnormality
An abnormal connection (fistula) between the esophagus and the trachea.
Accessory spleen
MedGen UID:
75619
Concept ID:
C0266631
Congenital Abnormality
An accessory spleen is a round, iso-echogenic, homogenic and smooth structure and is seen as a normal variant mostly on the medial contour of the spleen, near the hilus or around the lower pole. This has no pathogenic relevance.
Polysplenia
MedGen UID:
383959
Concept ID:
C1856659
Congenital Abnormality
Polysplenia is a congenital disease manifested by multiple small accessory spleens.
Asplenia
MedGen UID:
1830315
Concept ID:
C5779621
Anatomical Abnormality
Absence (aplasia) of the spleen.
Vocal cord paralysis
MedGen UID:
53047
Concept ID:
C0042928
Disease or Syndrome
A loss of the ability to move the vocal folds.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Short palpebral fissure
MedGen UID:
98067
Concept ID:
C0423112
Finding
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Depressed nasal tip
MedGen UID:
347214
Concept ID:
C1859717
Finding
Decreased distance from the nasal tip to the nasal base.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFeingold syndrome type 1

Recent clinical studies

Diagnosis

Gouveia I, Geraldo AF, Godinho C, Castedo S
BMJ Case Rep 2023 Mar 8;16(3) doi: 10.1136/bcr-2022-254366. PMID: 36889805Free PMC Article
Tedesco MG, Lonardo F, Ceccarini C, Cesarano C, Digilio MC, Magliozzi M, Rogaia D, Mencarelli A, Leoni C, Piscopo C, Imperatore V, Falco MT, Fontana P, Nardone AM, Novelli A, Troiani S, Seri M, Prontera P
Am J Med Genet A 2021 Apr;185(4):1204-1210. Epub 2021 Jan 14 doi: 10.1002/ajmg.a.62068. PMID: 33442900

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