Feingold syndrome type 1 (ORPHA:391641)
A rare, genetic congenital malformation syndrome 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 atresia (primarily esophageal and/or duodenal), and mild-to-moderate learning disability.
Epidemiology
The exact prevalence is unknown. Feingold syndrome type 1 (FS1) accounts for the vast majority of FS cases. An estimated 120 cases have been reported to date.
Clinical description
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.
Etiology
FS1 is caused by a mutation or deletion 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.
Diagnostic methods
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
Differential diagnosis of FS1 includes FS type 2 (FS2), VACTERL association, CHARGE syndrome, brachydactyly type A4 and Fanconi anemia.
Antenatal diagnosis
Prenatal testing is possible in FS1 families with a known MYCN mutation or deletion.
Genetic counseling
FS1 is inherited autosomal dominantly; however, most cases arise de novo. 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 anti-reflux 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
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.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Loïc DE PONTUAL | ITHACA*


                                * European Reference Network