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Feingold syndrome type 1
Feingold syndrome type 1 (FS1) is a rare inherited malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies.
ORPHA:391641Classification level: Subtype of disorder
- Brunner-Winter syndrome type 1
- Digital anomalies with short palpebral fissures and atresia of esophagus or duodenum type 1
- MMT type 1
- MODED syndrome type 1
- Microcephaly-digital anomalies-normal intelligence syndrome type 1
- Microcephaly-intellectual disability-tracheoesophageal fistula syndrome type 1
- Microcephaly-oculo-digito-esophageal-duodenal syndrome syndrome type 1
- ODED syndrome type 1
- Oculo-digito-esophageal-duodenal syndrome type 1
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal dominant
- Age of onset: Infancy, Neonatal
- ICD-10: Q87.8
- OMIM: 164280
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
The exact prevalence is unknown. FS1 accounts for the vast majority of FS cases. An estimated 120 cases have been reported to date.
Characteristic clinical findings of FS1 are present at birth with digital anomalies being the most frequent and including: brachymesophalangy (most commonly affecting the 2nd and 5th fingers), thumb hypoplasia and toe syndactyly. Microcephaly and facial dysmorphism (short palpebral fissures, micrognathia) are also noted in most cases. The most serious manifestations that are noted in approximately half of cases are esophageal and duodenal (rarely jejunal or anal) atresia, with or without tracheo-esophageal fistula. The presence of a fistula can be indicated by signs such as coughing, gagging, vomiting, abdominal distension and, in some cases, respiratory distress. Gastrointestinal atresia must be treated immediately or it can be fatal. Mild learning deficits can become apparent in early childhood but severe intellectual disability is very rarely seen. Additional anomalies include congenital cardiac malformations and renal hypoplasia that can lead to kidney failure if untreated. Short stature and hearing loss is also noted in some patients.
In 70% of cases, FS1 is caused by a mutation in the proto-oncogene MYCN (2p24.3). It encodes a protein with a basic helix-loop-helix domain that is expressed at various stages of human embryonic development. The remaining cases have a mutation in a yet to be discovered gene.
Diagnosis is based on characteristic clinical features and imaging studies. Gastrointestinal atresia can be seen with pre-natal or post-natal ultrasound or by MRI. Molecular genetic testing can identify a MYCN mutation, confirming a diagnosis of FS1.
Differential diagnosis of FS1 includes FS type 2 (FS2), VACTERL association, CHARGE syndrome, brachydactyly type A4 and Fanconi anemia.
Prenatal testing is possible in FS1 families with a known MYCN mutation.
FS1 is inherited autosomal dominantly and genetic counseling is possible.
Management and treatment
Extensive medical examinations are needed to identify possible anomalies of the heart or kidneys. Management of FS1 (and FS2) typically centers on surgical correction of the specific congenital anomalies (certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae. Gastrointestinal atresia requires prompt treatment involving IV fluid administration and surgery. Optimal surgical treatment of infants with esophageal atresia and tracheoesophageal fistula remains controversial and gastroesophageal reflux (GER) is extremely frequent in patients treated for the two conditions. GER is refractory to medical treatment and often requires antireflux surgery. Renal and cardiac anomalies should receive the standard treatments and prophylactic antibiotics may be beneficial. Special education is recommended for children and adults with learning deficits. Hearing loss should equally be monitored by an audiologist. Cochlear implants are possible in certain cases.
Prognosis depends on congenital malformations (especially cardiac and renal anomalies) present. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life.