Cat Cry Syndrome

A syndrome associated with a high-pitched, cat-like cry in the newborn period, severe mental retardation, facial anomalies, scoliosis, muscular hypotonia and congenital cardiac defects.

Cri-du-Chat Syndrome; Lejeune Syndrome, Deletion of Short Arm of Chromosome 5; Monosomy 5p.

First described in 1963 by the French pediatrician Jérôme Jean L.M. Lejeune.

Appears to be the most common human deletion syndrome, with an incidence of 1 in 15,000 to 1 in 50,000 live births. The frequency in patients with profound mental retardation (IQ<20) may be as high as 0.3%. A slight female predominance has been reported.

The syndrome arises from a partial or total deletion of the short arm of chromosome 5. A loss of the critical 5p15.2 region gives rise to most of the clinical features. The vast majority of cases are sporadic resulting from new mutations. Some arise from unbalanced translocations or parental chromosomal rearrangements. The severity of the syndrome is related to the extent of the chromosome deletion.

Unknown.

Based on the clinical picture plus molecular cytogenetic confirmation of 5p deletion with fluorescent in situ hybridization (FISH), which is considered the gold standard.

The name of the syndrome derives from the characteristic, high-pitched cry in infancy, which sounds similar to the mewing of a cat and is considered diagnostic for this disorder. The abnormal cry is mainly caused by anatomical anomalies of the larynx (long, curved and floppy epiglottis, laryngeal hypoplasia, laryngomalacia, asymmetric vocal cords, anterior approximation of the vocal cords with a large posterior commissure), however, in some patients the larynx was found to be structurally normal, which explains why some researchers believe that there may also be a neurological component involved in the abnormal cry. Mental retardation is most often severe. Central nervous findings include marked brainstem atrophy (mainly at the level of the pons) and cerebellar hypoplasia also involving the middle cerebellar peduncles. Generalized muscular hypotonia, poor sucking reflex, and respiratory distress may result in failure to thrive, which in combination with the commonly present intrauterine growth retardation results in postnatal growth retardation. The head usually is microcephalic with a round face due to full cheeks, downward slanting of the palpebral fissures, hypertelorism, low-set ears, depressed nasal bridge, microand/or retrognathia with a high-arched, narrow palate (cleft palate has also been described), and macrostomia. Up to 30% of these patients have congenital cardiac defects (most commonly atrial and/or ventricular septal defects, tetralogy of Fallot, pulmonary stenosis, and patent ductus arteriosus). Abdominal findings may include malrotation, megacolon, and inguinal hernias. The urogenital system may also be affected and findings include renal anomalies (e.g., renal agenesis, horsehoe kidney, hydronephrosis), hypospadias, cryptorchidism and testicular atrophy (although spermiogenesis is most often with intact). Skeletal features that have been reported are scoliosis, clubfoot, clinodactyly, and syndactyly of fingers and toes. Abnormal dermatoglyphics (e.g., simian crease) and premature graying of the hair may be present. Severely destructive behavioral problems (agression, self-mutilation) have been described repeatedly. Many patients die in early childhood mainly from respiratory distress (aspiration pneumonia) or the consequences of congenital cardiac defects.

Preoperative assessment should focus on signs for difficult airway management. Echocardiography should be performed to rule out cardiac defects. A chest radiograph is recommended in the face of recurrent aspiration pneumonias. If pneumonias are common and scoliosis is severe, echocardiography should also look for signs of cor pulmonale. Proton-pump inhibitors or H2-antagonists may be indicated to reduce gastric secretions. Assess kidney function (creatinine, blood urea nitrogen) and check serum electrolytes as well as a complete blood count. Patient cooperation is likely to be limited due to mental retardation and behavioral issues. Sedative premedication (careful if signs of cor pulmonale exist) and/or the presence of the primary caregiver for induction of anesthesia may be helpful.

Difficult direct laryngoscopy and tracheal intubation mainly resulting from micro-/retrognathia should be expected. Abnormal anatomy of the larynx may account for stridor and the cat-like cry in early infancy, but does probably not affect the ease of intubation. However, a smaller than expected endotracheal tube should be ready. Upper airway obstruction may result from the anatomical abnormalities in addition to muscular hypotonia indicating the potential need for prolonged postoperative mechanical ventilation. These patients have a high risk of gastroesophageal reflux and pulmonary aspiration, therefore a modified rapid sequence induction or awake fiberoptic intubation (which may be challenging in an uncooperative patient) have to be considered. Distinct cardiac defects require an adapted anesthesia technique. Other considerations concern difficulties in maintaining normothermia. The operating room should therefore be heated (especially during induction of anesthesia), and a forced-air convective warmer, heating blanket, and warmed infusions be used.

There is no reported association with malignant hyperthermia or succinylcholine-induced hyperkalemia. Muscular hypotonia may cause an exaggerated or unpredictable response to neuromuscular blockers. The use of a peripheral nerve stimulator and titration of neuromuscular blockers to effect is therefore recommended. Subacute bacterial endocarditis prophylaxis may be required.

Happy Puppet Syndrome: Characterized by severe developmental delay, speech impairment, movement dyskinesia, behavioral uniqueness of frequent laughter/smiling, apparent happy demeanor, and easily excitable personality, but short attention span. Seizures with onset before the age of 3 years. Prognathia, excessive chewing, and macroglossia. The craniofacial characteristics of cri-du-chat syndrome resemble this entity.

Cat Eye Syndrome: An inherited neurodevelopmental disorder with large phenotypic variability, ranging from nearly normal to severe malformations of many organs.