Meier‐Gorlin (ear‐patella‐short stature) syndrome: Growth hormone deficiency and previously unrecognized findings

Abstract

The association of microtia, midface hypoplasia, micrognathia, lower limb arthrogryposis, absent patella, and cryptorchidism was first described by Meier et al. [1959]. Gorlin et al. [1975] reported remarkably similar findings in a male patient associated with short stature. Boles et al. [1994], reporting on two sisters and reviewing six previously described patients, suggested the eponym Meier-Gorlin syndrome (MGS), which includes the triad of preand postnatal growth retardation, bilateral microtia, and patellar aplasia/ hypoplasia. Ear-patella-short stature syndrome (MGS) has become one of the increasingly recognized disorders and to date, at least cases of 35 patients have been published [Meier et al., 1959; Gorlin et al., 1975; Hurst et al., 1988; Cohen et al., 1991; Boles et al., 1994; Lacombe et al., 1994; Buebel et al., 1996; Teebi and Gorlin, 1997; Fryns, 1998; Loeys et al., 1999; Verhallen et al., 1999; Terhal et al., 2000; Bongers et al., 2001; Cohen et al., 2002; Feingold, 2002; Shalev and Hall, 2003; Dudkiewicz and Tanzer, 2004]. We observed a new patient with a previously unrecognized finding. The patient is the third child born to nonconsanguineous phenotypically normal parents who belong to the same endogamous tribe in Saudi Arabia. She was born normally at 36-week gestation and weighed 2.8 kg. Soon after birth, she developed severe respiratory distress that needed immediate intensive care. The patient was referred to King Faisal Specialist Hospital andResearchCenterwhere shewas diagnosedwith congenital left upper lobar emphysema, with generalized minimal emphysematous changes. In addition, she was noted to have microtia, micrognathia, and small-beaked nose. She underwent left upper lobectomy in the first week of life, and subsequently she had surgical resection of right middle lobe. Histopathological report indicated markedly dilated alveolar spaces. The patient’s general condition improved thereafter, though she still has hyperreactive airway disease. Chest radiographs showed variable infiltrateswith small thymus.One of the films showed soft tissue density posterior to the lower end of the sternum, suggestive of Morgagni hernia. Thyroid function tests, random GH and IGF-1 performed in early life were all unremarkable. Somatomedin C (IGF-1) and random growth hormone (rGH) at 20 months of age showed 6.7 mU/L and 37 MCG/L, respectively. Same tests, repeated at age 6, showed IGF-1 at 87 mg/L (normal: 82–262 mg/L) and rGH at 0.76mU/L (normal: 0–13 mU/L). GH stimulation test with Clonidine was safely performed in day and the patient was given an oral dose of Clonidine of 50 mg. Overall result showed definite GH deficiency (Table I). The patient was then started on recombinant GH on a weekly basis. The patient’s motor and mental developments were within normal since the age of 21⁄2years. Currently, she is 10 years old, doing well at normal school. Her most recent evaluation showed an apparently intelligent girl with OFC 49cm (<5%), weight 18.5 kg (<5%), and height 117.5 cm (<5%). She is slender, has a small face, frontal bossing, high hairline, long beaked nose, hypoplastic alae nasi, micrognathia, large upper central incisors, dental malalignment with a wide space between the upper central incisors, and bilateral microtia (Fig. 1a,b). She also has hyperextensible joints, dislocatable elbows with palpable clicks. Tanner (sex maturity rating, SMR) was in a preadolescent stage. Examination of other organs was unremarkable. Posterior and lateral radiograph of the knee joints showed absent patellae (Fig. 2). Hand radiograph for bone age showed retarded bone age (chronological age was 10 years, bone age according to Gruelich and Pyle standard is between 6 year 10 months and 7 years 10 months). Results of CT of the head, sonogram of abdomen/pelvis, and echocardiography were normal. Routine chromosomal analysis as well as FISH for 22q11 microdeletion was negative. The patient described here has classical manifestations of MGS, which include the triad of bilateral small ears, patellar aplasia/hypoplasia, and short stature. In addition, she has delayed bone age, which is another constant feature observed in almost all previous cases. Bongers et al. [2001], who described eight new patients and reviewed previously reported patients, found that MGS patients have a number of additional frequently encountered manifestations. These include microcephaly, small mouth, maxillary and mandibular hypoplasia, highly arched or cleft