INDIAN PEDIATRICS 539 VOLUME 43__JUNE 17, 2006

CASE REPORTS

Neonatal Hyperekplexia:The Stiff-Baby Syndrome

Neonatal hyperekplexia is a rare autosomaldominant startle disorder. Presenting soon afterbirth, it is often mistakenly diagnosed as spasticquadriparesis, epilepsy etc. While the long-termprognosis is relatively benign, sudden death due tosevere spasms have been seen in sporadic cases. Wereport a case of hyperekplexia with some typical andsome unusual findings.

Key words: Hyperekplexia, Startle, Stiff-babysyndrome.

Neonatal hyperekplexia is a rare auto-somal dominant disorder with onset soon afterbirth, characterized by exaggerated startleresponse, rigidity and assumption of a flexedfetal position. Non-habituating symmetricalflexor spasm in response to light tapping of thenose is the clinical hallmark of this disorder(1).Commonly associated features includeabnormal intrauterine fetal movements,feeding difficulties, nocturnal myoclonus,undue startle to loud noise or somatosensorystimulation, and hernias. Spasms may besevere enough to cause apnea, bradycardiaand death(2). We report a case ofhyperekplexia with some typical features

From the Jhanwar Pediatric Gastroenterology Cen-ter (JPGEC), Department of Pediatrics, SPM-CHI, SMS Medical College, Jaipur, India.

Correspondence to: Dr. S.D. Sharma, E-2 Doctor’sEnclave, Medical College Campus, JLN Marg,Jaipur 4, Rajasthan, India.E-mail: sdsharmajp@yahoo.co.in

Manuscript received: July 25, 2005;Initial review completed: September 20, 2005;Revision accepted: January 20, 2006.

along with a peculiar movement abnormalitynot commonly reported in such cases.

Case Report

A 9-month-old, female, first born to non-consanguineous parents was admitted with thesole complaint of episodic generalizedstiffness since birth. She was a full term, 3 kghome delivered baby who cried immediatelyfollowing birth. On life day 2, her mothernoticed stiffness of the body during handlingand a startle to the lightest of auditory or tactilestimuli. The stiffness decreased when the childwas asleep. There was no history of feedingdifficulties, clonic movements or cyanosis.There was history of operation for umbilicalhernia at the age of 3 months. Develop-mentally child was normal except of a milddelay in gross motor fields. There was nosuggestive family history on either side.

On CNS examination, rigidity was seen inall muscle groups including trunk andabdominal wall. Deep tendon reflexes werenormal. The patient held herself in a flexedposture, with clenched fists and had an anxiouslook. Exaggerated nonhabituating startleresponse along with increased period ofhypertonicity were demonstrated on tappingof the nose. She also had stereotypic move-ments in the form of rocking herself to and frowhile lying supine, for long periods of timeespecially when disturbed by excessive handling, loud or sudden sound and on separationfrom parents. Routine counts and muscleenzyme markers, including creatininephosphokinase-MB (CPK-MB), SGOT andLactate dehydrogenasen (LDH) were normal.Muscle biopsy and EMG were also normal.Sonography brain revealed no abnormality.EEG showed no epileptiform discharges.

In light of the suggestive history andnormal investigations a diagnosis of “stiff-baby syndrome” was suspected and thera-

S.D. SharmaAnurag SarnaSagori Mukhopadhyay

INDIAN PEDIATRICS 540 VOLUME 43__JUNE 17, 2006

CASE REPORTS

peutic trial of clonazepam started at a dose of0.1 mg/kg. Dramatic response was noted within72 hrs with a decrease in tone, lessened startleresponse and straitening of the body to anormal posture.

Self-limiting course of the disease and itsgenetic mode of inheritance, with probabilityof the other siblings being affected, wasexplained to parents.

At one-year follow-up the child has showncontinued improvement in the form of in-creased spontaneous movements, decreasedstartle and achievement of most of the normalmilestones. However, she continues to main-tain a slightly flexed posture and walking re-mains unstable with a tendency to sudden falls.Language development too is mildly delayed,but socially she is active and comparable to hersiblings.

Discussion

Hyperekplexia or “startle disease” is anonepileptic disorder characterized by twoabnormal forms of response to unexpectedauditory, visual and somesthetic stimuli,namely sustained tonic spasm (tonic extensionof both upper and lower limbs or flexion ofupper with extension of lower limbs) and theexaggerated startle response (which is a basicalerting reaction with stereotyped featuresconsisting of eye blinking, facial grimacing,flexion of head, elevation of shoulders, andflexion of elbows, trunk and knees)(3).

Additional features include generalizedhypertonia decreasing with sleep withhypokinesia, nocturnal myoclonus, increasedincidence of congenitally dislocated hips,feeding difficulties with increased incidenceof difficult labor and abnormal intrauterinemovements(4). Hernias, requiring operativeintervention, possibly caused by the per-sistently raised intra-abdominal pressure, arecommon, as was present in this case(5,6).

Family history is usually present, thoughsporadic cases have been documented(7). Ourcase had no such history. She had both theabnormal responses, qualifying as a majorform of the disease. The rocking movementsseen were unusual and no mention of suchassociation was found in previously publishedliterature.

Risk of death from apnea caused by severespasms has been documented and these can beaborted by forced flexion of the head and legsover the trunk(2). Rigidity decreases spon-taneously by 2-3 yrs of age when increase inspontaneous activity occurs. However, insome cases mild stiffness reappears inadolescence or adult life and spasms mayagain be provoked by startle(6). Such episodesare a source of injury. Also the unpredictabletiming and outward manifestations of attacksin form of sudden falls or undue startle maymake outdoor activities both dangerous andembarrasing resulting in considerable socialdysfunction(5). Delayed motor milestones arepresent while cognitive function normallyremains unaffected(8), though low intelli-gence has been noted in some studies(9).

Diagnosis is mostly clinical; EMG mayshow shortened latencies with continuouselectrical activity at rest, when present itmaybe used to monitor progress and responseto therapy. Initial spike at frontocentral regionfollowed by slow waves and desyncronizationare sometimes seen in EEG. Muscle biopsiesare normal.

Hyperactivity of the cortical neurons,decreased sub cortical inhibitory responsesand serotonergic pathways has been proposedas pathogenic pathways(1). Linkage analysisdemonstrated linkage of disorder with5q33-35 locus. There is usually a mutation onthe α – 1 subunit of the inhibitory glycinereceptors (GLRA1) in the caudal pontine

INDIAN PEDIATRICS 541 VOLUME 43__JUNE 17, 2006

CASE REPORTS

reticular formation leading to neuronalhyperexcitability, by changing the chlorideconductance. Low CSF GABA levels havebeen shown, suggesting a mechanism for theefficacy of clonazepam, a GABA agonist(10).Proton magnetic resonance spectroscopicimaging (MRSI) has shown decreased N-acetylaspartate, choline derivatives andcreatinine in the frontal regions of brain.

The disease must be distinguished fromother causes of neonatal hypertonia such astetany, tetanus, Schwartz-Jample syndromeand severe perinatal asphyxia(6).

Therapeutic response to benzodiazepamgroup is dramatic enough to be diagnostic.

Diazepam and clonazepam are consideredthe drugs of choice. Valproic acid, 5-hyroxy-tryptophan and piracetam have also producedsome benefits(8).

Contributors: SM carried out the literature reviewand drafted the manuscript, AS reviewed themanuscript and SDS was responsible for thediagnosis, supervision and overall management. Hewill stand as guarantor for the report.

Funding: None.

Competing interests: None stated.

REFERENCES

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2. Vigevano F, Capua M D, Bernardina BD.

Startle Disease: An avoidable cause of suddeninfant death. The Lancet 1989; 28: 216.

3. Chaves-carabello E. Syncope and paroxys-mal disorders other than epilepsy. In:Swaimann KF, Ashwal S (eds). Pediatricneurology: Principles and Practice. 3rd edn.Mosby, USA. 1999; p.768-769.

4. Leventer RJ, Hopkins J, Shield LK. Hyperek-plexia as cause of abnormal intrauterinemovements. Lancet 1995; 348: 461.

5. Suhren O, Bruyn GW, Tuynman JA.Hyperekplexia-a hereditary startle syndrome.J Neurol Sci 1966; 3: 577-605.

6. Brett EM, Lake BD. NeuromuscularDisorders: Primary muscular disease andanterior horn cell disorder. In: Brett EM (ed).Pediatric Neurology. 3rd edn. ChurchillLivingston: London. 1997; p.77.

7. Hayashi T, Tachibana H, Kajji T.Hyperekplexia: pedigree studies in twofamilies. Am J Med Genet 1991; 40:138-143.

8. Singer HS. Movement disorder in children.In: Jankovic JJ, Tolosa E (eds). Parkinson’sDisease and Movement Disorder. 4th edn.Lippincott Williams and Wilkins: Phildelphia,USA 2002; p. 454-455.

9. Andermann F, Daniel LK, Andermann E,Quesney LF. Startle disease or Hyperekplexia:further delineation of the syndrome. Brain1980; 103: 985-987.

10. Dubowitz LMS, Bouza H, Hird MF, Jaeken J.Low cerebrospinal fluid concentration ofgamma amino butyric acid in startle disease.Lancet 1992; 340: 80-81.