Introduction

The Cri-du-chat Syndrome (CdCs) is a rare genetic syndrome first described by Jerome Lejeune in 1963, characterized mainly by the high pitched cat like cry. The prevalence of CdCs was varied in between 1:15,000 to 1:50,000 in live births and more common in female gender with a ratio of 4:3 [1, 2].

Children with cri-du-chat syndrome usually present with low weight (mean weight 2614 g), microcephaly (mean head circumference 31.8 cm), micrognathia (96.7%), typical high pitched cat like cry (95.9%), abnormal dermatoglyphics (transverse flexion creases) (92%), epicanthal folds (90.2%), large nasal bridge (87.2%), rounded face (83.5%), hypertelorism (81.4%), down-turned corners of the mouth (81.0%), downward slanting palpebral fissures (56.9%), and low-set ears (69.8%)0.1 The condition may be accompanied by developmental and cognitive delays, poor spatial awareness, impaired ambulation, and poor sensori-motor skills. Other associated problems described include cardiovascular, renal, gastrointestinal, neurological abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism [1].

Recent literatures show that autistic behaviours are common in various genetic disorders [3]. Fatigue level of children with cri du chat syndrome was associated with the expression of autistic features [4].

Here we are presenting a case report of a patient diagnosed with CRI DU CHAT syndrome with bilateral sensorineural hearing loss.

Case Report

A 3-year-old syndromic male child presented to our institute with complaints of delayed developmental milestones, improper hearing-not responding to oral commands and speech delay.

Neonatal History

Baby was born at 34 weeks of gestation by normal delivery. He was noted to have respiratory distress soon after birth and transferred to intensive care unit. Baby was noted to have wide inter-canthal distance, epicanthic folds, upward slant of both eyes, shrill cry, bilateral simian crease and bilateral club foot. Overall body tone was normal.

Physical Examination of the Child

General physical examination of child showed microcephaly, round face, hypertelorism, downward slanting palpebral fissure, down-turned corner of the mouth, retrognathia (Figs. 1, 2, 3, 4 and 5). Nose examination revealed large nasal bridge. Ear examination revealed low set ears, right external auditory canal stenosis, left external auditory canal normal (Fig. 6). Right tympanic membrane was partly visualized and left tympanic membrane was intact. Audiological assessment like ABR showed Responses to air conducted clicks could be obtained only at 90dBnHL n right ear and peaks were absent in left ear. Results of ABR are consistent with Bilateral severe to profound Hearing Loss (Fig. 7). OAE reports came as negative for both ears.Behvioural Audiometry showed the following results (Table :1).

Fig. 1
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Appearance of a CRI-DU-CHAT syndrome child

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Fig. 2
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Transverse flexion crease

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Fig. 3
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Microcephaly and retrognathia observed in the child

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Fig. 4
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Appearance of low set ears, large nasal bridge, rounded face, hypertelorism, down-turned corners of the mouth, downward slanting palpebral fissures

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Fig. 5
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Bilateral club foot

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Fig. 6
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Stenosis of right external auditory canal, Normal left external auditory canal

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Fig. 7
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BERA

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Table 1 Behavioural Audiometry
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Chromosomal microarray showed a loss involving chromosome 5 within cytoregion p15 (Fig. 8).

Fig. 8
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Chromosomal microarray analysis was done which revealed abnormality

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Discussion

Cri du Chat Syndrome (CdCS) is a rare genetic disease which occurs due to a partial deletion of chromosome 5 in its short arm (5p- ) with incidence of 1:15,000 to 1:50,000 live-born infants [1].The person usually present with severe intellectual delay, psychomotor delay, language impairment and behavioral abnormality [4]. The child has a typical cat-like cry results due to small, narrow and diamond-shaped larynx and small, flabby epiglottis and alterations in the nervous system [5]. The phenotypical features are microcephaly, hypertelorism, round face, wide nasal bone, downward slanting of palpebral fissure, epicanthal folds, down-turned mouth corners, low set ears, under developed mandible, transverse flexion creases [6]. In literature a case has been reported in which the child had a neonatal history of cyanosis, asphyxia, hypotonia and impaired suction and abnormalities like cardiac, renal and neurological malformations, preauricular tags, cryptorchism, hypospadias and syndactyly [7].

In a study performed by Heung et al.,where a family with five individuals showed chromosomal rearrangements involving 5p which was due to a rare maternal complex chromosomal rearrangements.

A 4 and half year old brother and a 2 and half year old sister served as the starting points for this genetic study.They did not show diagnostic cat cry during infancy, instead presented with developmental delay, dysmorphic and autistic features and intellectual delay [8]. Chromosomal microarray in this patient showed a loss involving chromosome 5 within cytoregion p15.A clinical diagnosis of Cri du chat syndrome was made Physical examination of the child in our study revealed microcephaly, round face, hypertelorism, downward slanting palpebral fissure, down-turned corner of the mouth, retrognathia, large nasal bridge. Ear examination revealed low set ears, right external auditory canal stenosis.

Cornish et al assessed developmental and behavioral characteristics in 27 children with cri du chat syndrome which showed that none of the patients had neurological problems like fits or epilepsy.Four children had abnormal vision but none of the patients had abnormal hearing [9]. But in our study where the patient had bilateral sensorineural hearing loss.

The audiological finding in the child with cri-du-chat syndrome are hyperacusis and high frequency sensorineural hearing loss on both sides.8,9 The reason for sensorineural hearing loss is the gene responsible for cochlear development is located in the 5P- gene [10]. The investigations like Otoacoustic emission (OAE) and Auditory brainstem response (ABR) showed failure response and indicated hearing loss in the patients with cri-du-chat syndrome [11]. The individual with cri-du-chat syndrome has absent or atypical ABR response with variable hearing loss severity and worst speech understanding [12]. Swanepoel D et al. reported that there is a mismatch in the bahavioural response and electrophysiological results and failed response in both OAE and ABR [13].

Baccichetti et al. reported 5p- syndrome had mild high frequency hearing loss in pure tone audiogram [9]. In our study cytogenic microarray analysis showed a loss of chromosome 5 within cytoregion p15.33p14.3 indicating monosomy of this region.

In our patient OAE reports came as negative. Behavioral audiometry showed findings in consistent with similar previous studies which is mentioned below.

In view of age of the patient, pure tone audiometry could not be performed. Hence BERA was performed and the report showed Bilateral severe to profound Hearing Loss.

On Behavioral Observational Audiometry, response was absent even for hard level sound stimulus.

The child is in periodic follow up with us and has been counselled for hearing and speech rehabilitation.

Conclusion

Cri-du-chat syndrome is a rare genetic disorder resulting in various physical and psychological abnormalities due the deletion of chromosome 5P-. We encountered a case of cri-du-chat syndrome having external auditory canal atresia, bilateral sensorineural hearing loss with speech delay which is of concern. A multidisciplinary approach is required for diagnosis and management of such patients. Otological management is early identification of hearing loss and speech rehabilitation. Awareness about antenatal screening for congenital anomalies and genetic counselling is necessary among the general population.