Elsevier

Mayo Clinic Proceedings

Volume 76, Issue 12, December 2001, Pages 1219-1224
Mayo Clinic Proceedings

Original Article
Ciliary Dyskinesia Associated With Hydrocephalus and Mental Retardation in a Jordanian Family

https://doi.org/10.4065/76.12.1219Get rights and content

Objective

To describe the presentation and genetic transmission of ciliary dyskinesia syndrome associated with hydrocephalus and mental retardation in 3 generations of a family.

Patients and Methods

A large Jordanian family included 9 individuals in 3 generations with recurrent pulmonary infections; 4 male siblings have been diagnosed as having mental retardation, and a maternal uncle was believed to have been similarly affected. Chromosome analysis of the family showed a normal karyotype.

Results

Electron microscopy of the nasal cilia from 3 affected siblings showed features of primary ciliary dyskinesia. Computed tomographic scans of the brains of all 4 affected siblings showed hydrocephalus.

Conclusions

The recurrent pulmonary infections and hydrocephalus in this large Jordanian family are likely related to ciliary dyskinesia, which appears to follow an autosomal recessive mode of inheritance. The unusual presentation of ciliary dyskinesia, hydrocephalus, and mental retardation may be due to a new genetic mutation.

Section snippets

PATIENTS AND METHODS

This report concerns a large family that lived in refugee camps in Jordan. The parents (II-5 and II-6 in Figure 1) of the 4 affected siblings were first-degree cousins and had 15 offspring: 10 males and 5 females (Figure 1). The father (II-6), a long-term smoker, had chronic obstructive pulmonary disease. The mother (II-5) had bronchial asthma and nasal polyposis. Three children (III-4, III-12, and III-15), 2 females and 1 male, died at the ages of 2 months, 2 years, and 2 years, respectively,

DISCUSSION

Some of the important systemic causes of recurrent pulmonary infections such as immunodeficiency and cystic fibrosis4, 5 were ruled out in the affected individuals in generation III of this family. In the early 1970s, a congenital defect of the respiratory cilia was recognized as a cause of recurrent sinopulmonary infections in patients with Kartagener syndrome.2, 3, 6, 7 The patients described herein showed the absence of dynein arms in some cilia8, 9, 10 and disorientation of the central

REFERENCES (37)

  • M Greenstone et al.

    Ciliary function in health and disease

    Br J Dis Chest

    (1985)
  • RD Miller et al.

    Kartagener's syndrome

    Chest

    (1972)
  • JR Vevaina et al.

    Correlation of absent inner dynein arms and mucociliary clearance in a patient with Kartagener's syndrome

    Chest

    (1987)
  • BA Afzelius

    A human syndrome caused by immotile cilia

    Science

    (1976)
  • R Eliasson et al.

    The immotile-cilia syndrome: a congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility

    N Engl J Med

    (1977)
  • RB Johnston

    Recurrent bacterial infections in childhood

    N Engl J Med

    (1984)
  • HY Reynolds

    Respiratory infections may reflect deficiencies in host defense mechanisms

    Dis Mon

    (February 1985)
  • P Camner et al.

    Evidence of congenitally nonfunctioning cilia in the tracheobronchial tract in two subjects

    Am Rev Respir Dis

    (1975)
  • H Levison et al.

    Pathophysiology of the ciliary motility syndromes

    Eur J Respir Dis Suppl

    (1983)
  • Y Watanabe et al.

    How can we detect patients with immotile cilia syndrome?

    Eur J Respir Dis Suppl

    (1983)
  • AJ Veerman et al.

    The immotile cilia syndrome: phase contrast light microscopy, scanning and transmission electron microscopy

    Pediatrics

    (1980)
  • A Rutman et al.

    Ciliary disorientation: a possible variant of primary ciliary dyskinesia

    Thorax

    (1993)
  • CF Rayner et al.

    Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome

    Am J Respir Crit Care Med

    (1996)
  • MA Greenstone et al.

    Ciliary dyskinesia with normal ultrastructure

    Thorax

    (1983)
  • M Greenstone et al.

    Primary ciliary dyskinesia: cytological and clinical features

    Q J Med

    (1988)
  • R Gershoni-Baruch et al.

    Immotile cilia syndrome including polysplenia, situs inversus, and extrahepatic biliary atresia

    Am J Med Genet

    (1989)
  • VG Engesaeth et al.

    New associations of primary ciliary dyskinesia syndrome

    Pediatr Pulmonol

    (1993)
  • N Oggiano et al.

    Respiratory distress in a newborn with primary ciliary dyskinesia, situs inversus and Turner syndrome

    Minerva Pediatr

    (1994)
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