Reynolds Neri Hermann Syndrome

At a glance

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 brain stem atrophy (gait ataxia). Considered part of RASopathies.

Synonyms

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

History

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

Incidence

Extremely rare. One hundred patients have been presented in the medical literature but multiple unreported cases are known to exist. Prevalence in Japan 1:810,000.

Genetic inheritance

Autosomal dominant, sporadic. Gene map locus at 12q24.1; however, most cases reported are considered sporadic on BRAF, MEK1 (MAP2K1) or 2 (MAP2K2), or KRAS MEK. Associated with advanced paternal age.

Pathophysiology

Considered part of RASopathies, which are caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway, which also include ☞Noonans, ☞Costello, and Legius Syndromes.

Diagnosis

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

Clinical aspects

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, brain stem atrophy). Hepatosplenomegaly and ectopic testes can also occur. Tendency to develop benign (giant cell tumors) or malignant (hepatoblastoma, lymphoma, acute lymphoblastic leukemia) tumors.

Precautions before anesthesia

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

Anesthetic considerations

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. Exercise caution when mobilizing the occipital-cervical junction if there is an Arnold-Chiari malformation. Avoid hyperthermia because of hypohidrosis. Perimedullar anesthesia is not contraindicated, but one must consider the risk because of the neuroectodermal origin of most lesions.

Pharmacological implications

Prophylactic antibiotics must be considered as indicated in case of cardiopathy. Antiepileptic and cardiac drugs must be continued until ...