Reynolds Neri Hermann Syndrome

A rare syndrome characterized by postnatal short stature with cardiac defect (atrial septal defect, pulmonic stenosis) and craniofacial anomalies (facial features similar to Noonan syndrome). Other features include relative macrocephaly, micrognathia, high-arched palate, splenomegaly, hypotonia, hypertonia, hydrocephalus and raised intracranial pressure, and brainstem atrophy (gait ataxia).

Cardio-Facio-Cutaneous Syndrome; CFC syndrome; Facio-Cardio-Cutaneous Syndrome.

First described in 1986 by James F. Reynolds, American geneticist, Giovanni Neri, Italian geneticist, and Jürgen Herrmann, German physician.

One hundred patients have been presented in the medical literature.

Autosomal dominant, sporadic. Gene map locus at 12q24.1; however, most cases reported are considered sporadic. Associated with advance paternal age.

Clinical. The manifestations include congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure.

This short-stature patient can present with cardiac lesions (78% of cases, pulmonary valve/artery stenosis, congenital cardiac anomaly, atrial septal defect), cephalic malformations (ptosis, short neck, brittle hair, microcephaly, epicanthic folds helix, high forehead, bitemporal constriction, thickened/depressed nasal bridge, micrognathia, sparse/absent scalp hair, nystagmus, palate deformations), orthopedic deformations (hyperextensible fingers, multiple palmar creases, multiple plantar creases), cutaneous lesions (severe atopic dermatitis, ichthyosis, hyperkeratosis, hypohidrosis), and neurological disturbance (mild to moderate mental retardation, seizures, hypotonia, hypertonia, hydrocephalus, cortical atrophy, frontal lobe hypoplasia, brainstem atrophy). Hepatosplenomegaly and ectopic testes can also occur.

Evaluate cardiac lesion (chest radiograph, echocardiography, ECG, radionuclide imaging if necessary); neurological function (clinical, EEG, somatosensory evoked potentials, CT).

Careful intraoperative positioning is needed; in case of cardiopathy, perioperative cardiac monitoring should be used and adapted anesthetic technique for the cardiac anomaly. Direct laryngoscopy and tracheal intubation can be difficult because of facial deformation. Fiberoptic intubation may be required. Avoid hyperthermia because of hypohidrosis. Perimedullar anesthesia is not contraindicated but one must consider the risk because of the neuroectodermal origin of most lesions.

Prophylactic antibiotics must be considered as indicated in case of cardiopathy. Antiepileptic and cardiac drugs must be continued until the day of the surgery. Consider interaction between antiepileptic treatment and anesthetic drugs. Avoid muscle relaxants until airway is secured.

Noonan syndrome: Characterized by a distinctive facial appearance similar to the CFC syndrome. The clinical features include webbing of the neck, short stature, characteristic abnormalities of the chest (pectus carinatum and/or pectus excavatum), congenital heart defects (pulmonary stenosis), and/or other abnormalities of which the most relevant are thrombocytopenia and coagulation factor deficiencies. Abnormally large and/or present in unusual places bruising and bleeding are common. It is inherited as an autosomal dominant transmission. There is disagreement in the medical literature whether Noonan and CFC syndromes are distinct medical conditions.

Costello syndrome: Characterized by short stature, distinctive facial characteristics (excessive loose skin on the neck, palms of the hands, fingers, and soles of the feet), perioral papillomata and mental retardation. Macrocephaly, depressed nasal bridge, abnormally wide nostrils, low-set ears with large, thick lobes, palmoplantar hyperkeratosis, and the potential for congenital heart defects. Most cases occur sporadically with no family history of the disorder. Such cases are thought to represent new dominant gene mutations.