American Journal of Medical Genetics 40:488-492 (1991)

Neurological Aspects of del(lq) Syndrome Keiko Murayama, Robert S. Greenwood, Kathleen W. Rao, and Arthur S. Aylsworth Departments of Neurology (KM, RSG), Pediatrics (RSG, ASA, KWR), the Brain and Development Research Center (ASA, KWR), and Pathology (KWR), School of Medicine, University of North Carolina, Chapel Hill We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(l)(q43)).They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-likebehavior. They avoid eye contact,show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitchedshrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal l q deletions.

KEY WORDS: deletion 1q42-43,human-chromosome-pair-1, behavior, autism, genetics INTRODUCTION Terminal deletion of the long arm of chromosome 1 causes a characteristic combination of minor anomalies and neurologic signs [Johnson et al., 1985; Meinecke and Vogtel, 1987; Watson et al., 19861. The syndrome has been reported in detail, but little attention has been paid to the neurological manifestations. We have evaluated three children with del(1q) syndrome with special interest in their neurological problems. All of these patients had similar autistic-like behavior and unusual phonations that have not been described previously.

Received for publication September 21, 1990; revision received January 25, 1991. Address reprint requests to Keiko Murayama, Department of Neurology, CB 7025, Burnett Womack Building 751, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599-7025.

0 1991 Wiley-Liss, Inc.

CLINICAL REPORTS Three new patients with de novo del(1q)syndrome are reported. The clinical features of these three patients are summarized in Tables I and 11. They all had minor anomalies typical for del(1q) syndrome (microcephaly, upslanting palpebral fissures, short broad nose, downcurved mouth, micrognathia, short neck, and submandibular fat) (Fig. 1)[Johnson et al., 1985; Meinecke and Vogtel, 1987; Watson et al., 19861.Lymphocyte chromosome analysis (metaphase spreads stained with trypsinGiemsa and analyzed at approximately the 550 band level) showed that all three patients had 46,XX,del(l) (q43) (Fig. 2). The deletion was in the same small region of chromosome 1 in each patient (Fig. 3). All of the deletions were de novo. The behavior and voice of each patient was recorded by video and audio tape recorder at several clinic visits. All three patients manifested autistic-like behavior and abnormal phonation. They each had repetitive stereotypic purposeless movement, such as head or handshaking, thigh tapping, head turning, flapping hands in the air, and finger manipulation with persistent visual attention. Their finger manipulation bears a likeness to the hand-wringing seen in Rett syndrome but is much finer in each movement. The patients frequently assumed a posture of elbow and hip flexion and knee extension. Although they had independent fine finger movements, they did not make purposeful, voluntary finger movements. These patients visually attended to bright light or simple, high-contrast patterns, but frequently avoided eye contact with others by looking upward. They expressed little emotion and rarely cried. All three patients exhibited abnormal patterns of phonation. In early life they were reported to have a highpitched, shrill cry similar to that in cri-du-chat syndrome, but later their phonation changed to a pattern of harsh, strained, glottal stridency followed by deep inspiration. At the point of study patient 1was in the latter stage and patient 2 and patient 3 were in a transitional stage, alternately presenting both types of phonation. In response to mechanical sound or physical stimuli, the patients would change the pitch of monotonous vocalization or stop vocalizing. This vocalization occurred only while they were awake. An analysis of their phonation showed no labial, nasal, or lingual sounds. Patients 2 and 3 had cleft palates and all three patients showed poor palatal, pharyngeal and laryngeal movements. They had frequent drooling, gurgling, and bruxism.

del(1q) Syndrome

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TABLE I. Summary of Clinical Measurement and Laboratory Findings Age at study Body Weight Height Head circumference (OFC) Birth weight Birth length Birth OFC Gestational age Fingertip dermatoglyphics L R CT scan or MRI of brain EEG; epileptic discharge Bone radiography

Patient 1" 91/12 years 21 kg (

Neurological aspects of del(1q) syndrome.

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and n...
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