American Journal of Medical Genetics 42:813-814 (1992)
Brief Clinical Report Autosomal Dominant Congenital Laryngomalacia Mordechai Shohat, Yakov Sivan, Ellen Taub, and Shmuel Davidson Departments of Medical Genetics (M.S., E.T.), Pediatric Pulmonology (Y.S.), and Neonatology (S.D.), Beilinson Medical Center, Sackler School of Medicine, Tel Auiu University, Petah Tiqva,Israel
A family is presented in which congenital stridor due to laryngomalacia was evident in 9 individuals through 3 generations. This report confirms the autosomal dominant transmission of at least one type of laryngomalacia. KEY WORDS: eyelashes, cleft palate, congenital stridor INTRODUCTION Although laryngomalacia is not uncommon, only one previous report has described the hereditary occurrence of laryngomalacia [Shulman et al., 19761.In that family 3 of 5 sibs were severely affected; their mother experienced respiratory difficulties in the first year of life [McKusick, 19903.We confirm the autosomal dominant transmission of congenital stridor due to laryngomalacia. CLINICAL REPORT In this family, transmission of congenital stridor was evident in at least 3 generations (Fig. 1).The parents of the propositus are Iranian Jews, first cousins once removed (Fq affected offspring is 1/32). Patient No. 1 (V-4) The propositus, S.A., was a 3,600-g male, term product of a normal pregnancy and uncomplicated delivery to a 33-year-old mother. Apgar scores were 9 a t one and 9 minutes. At birth he had a cleft lip and palate and marked respiratory stridor with sternal and subcostal retractions. The patient had long eyelashes (Fig. 2). Otherwise he was normal on physical examination. A chest radiograph taken shortly after birth was also normal. The stridor (cog-wheelinspiratory noise) persisted; a t 6 months he underwent direct fiberoptic laryngoscopy. The airway from the nares to the hypopharynx was open on inspiration and expiration. Obstruction was
evident a t the laryngeal orifice. A narrow omega tubeshaped epiglottis which collapsed on inspiration was observed. The aryepiglottic folds were sucked down onto the glottis on inspiration so that the larynx became obstructed and then expanded during expiration. The vocal cords and immediate subglottic region were normal. Barium swallow and radiographic imaging of the trachea did not show any abnormality or tracheal compression. At age 7 months, the cleft lip and palate was surgically corrected and the infant, who is now 8 months old, still manifests stridor at rest.
Patients No. 2, 3 (V-1, V-3) These 6- and 4-year-old children, sibs of the propositus, were also term products of a normal pregnancy and delivery. They also had stridor and cyanosis a t birth. Chest radiograms and barium swallow were normal. Physical examination did not show other anomalies. Although the stridor gradually improved over the first 2 years, these patients continued to manifest mild transient stridor and hoarseness during episodes of upper respiratory tract infections and strenuous activities. One such episode in patient V-1 was documented by us. Patients IV1, IV2, IV3, IV4, and 1111 The mother of the propositus, 3 of her sibs, and her mother had had congenital stridor which persisted for the first 2 years of life and gradually resolved. Today they are in good health with normal voice, normal stature, and no respiratory problems. It is possible that other individuals in this family have been affected; however, information could not be obtained. No one in this family was brain damaged or had cerebral palsy due to hypoxia, required tracheostomy, or developed obstructive/respiratory cor pulmonale. The family history is negative for other individuals with cleft lip. Conspicuous eyelashes were evident in the propositus, all of his sibs, his mother, and other relatives from the mother’s side with or without laryngomalacia.
DISCUSSION This family demonstrates familial transmission of Received for publication March 27,1991; revision received June congenital stridor, based on the laryngoscopic findings 11, 1991. Address reprint requests to M. Shohat, M.D., Medical Genetics, in the propositus and the history of stridor in the others. The clinical presentation, the age at appearance and Beilinson Medical Center, Petah Tiqva 49100, Israel.
0 1992 Wiley-Liss, Inc.
Shohat et al.
Fig. 1. The pedigree demonstrates dominant transmission of congenital laryngomalacia.
resolution of symptoms, and the benign nature of the disorder are compatible with laryngomalacia [Phelan et al,, 19821,which is the most common cause of congenital stridor. Autosomal dominant transmission seems to be the most appropriate model to explain the segregation of the stridor in this family. Because no male-to-male transmission was observed in this family, x-linked dominant inheritance is also possible. Shulman et al. [19761described 3 of 5 sibs with severe laryngomalacia requiring tracheostomy neonatally. Pathologic studies of tracheal cartilage showed hypercellularity and peculiarity of the matrix. The mother of this sibship experienced respiratory difficulties in the first year of life; however, none of her 13 sibs had evidence of respiratory difficulties or stridor. In comparison to the severe manifestations presented by Shulman et al. [ 19761,no one in the family reported herein had brain damage or cerebral palsy due to hypoxia requiring tracheostomy. No other families with familial transmission of congenital stridor have been reported. Although lar-
Fig. 2. In addition to the laryngomalacia, the propositus had cleft lip and cleft palate. Long eyelashes were noted also in his sibs, mother, and other relatives from the mother’s side with and without laryngomalacia.
yngomalacia may be heterogenous, our case confirms the existence of a t least one type that is dominantly inherited.
REFERENCES McKusick VA (1990): “Mendelian Inheritance in Man; Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes.” 9th edition. Baltimore: The Johns Hopkins Univ. Press, p. 561. Phelan PD, Landau LI, Olinsky A (eds) (1982):“Respiratory Illness in Children.” London: Blackwell Scientific Publications, pp 117-120. Shulman JB, Hollister DW, Thibeault DW, Krugman ME (1976): Familial laryngomalacia: A case report. Laryngoscope 86934-91.