Many epidemiological studies have indicated that inbreeding has little or no effect on the incidence of cancer. Due to the high prevalence of consanguinity in Qatar (54%), its influence may nevertheless be of special importance.The aim of this study was to examine whether parental consanguinity affects the risk of cancer in a local Arab highly inbred population.Matched case-control study.The study was carried out in Al-Amal cancer hospital and primary health care centers in Qatar over a period from August 2008 to February 2009.The study included 370 Qataris and other Arab expatriates with various types of cancers and 635 controls matched by age and ethnicity. A questionnaire that included socio-demographic information, type of consanguinity, medical history, and tumor grade was designed to collect the information of cases and controls.The study revealed that the rate of parental consanguinity was similar in both cases (29.5%) and controls (29.9%) with a higher inbreeding coefficient in controls (0.017-/+0.03), compared to cancer patients (0.0155-/+0.03). Other Arab expatriates had a higher incidence of cancer (61.1%) than Qataris (38.9%). The inbreeding coefficient was higher in male cancer patients (0.0189-/+0.03), but lower in female cancer patients (0.014-/+0.03) as compared to controls. Controls were more inbred in the overall studied subjects (23.6%) and women (23.8%) than cases. The coefficient of inbreeding was lower in patients with breast (0.014), skin (0.012), thyroid (0.008) and female genital (0.014) cancers, whereas it was higher in cases for leukemia and lymphoma (0.018), colorectal (0.025) and prostate (0.017), with no significant difference between cases and controls. No significant differences were observed between cases and controls in the parental consanguinity, mean coefficient of inbreeding and proportion of more inbred subjects.The study findings revealed that although the consanguinity rate is high in our Arab population, it has no effect on the incidence of cancers overall. However, there was an increased risk found for leukemia and lymphoma, colorectal and prostate cancer groups, but a reduced risk in breast, skin, thyroid and female genital cancer groups.
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 pre- and 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 and Research Center where she was diagnosed with 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 infiltrates with 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 µg/L (normal: 82–262 µg/L) and rGH at 0.76 mU/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 µg. 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 2½ years. 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. a: Patients full face, (b) profile showing microtia. 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). Knee radiograph showing absent patella. 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 palate, and early feeding problems. Skeletal abnormalities, including slender long bones, abnormal glenoid fosse, dislocated radial heads, hook-shaped clavicles, thoracic and joint abnormalities, were also relatively common. Appearance of clitoromegaly, hypoplastic labia majora/minora, hypospadias, cryptorchidism, and hypoplasia of mammary glands have been noted also in a number of cases. No specific respiratory disorder had been noted previously, but early nonspecific respiratory problems were not uncommon. Our patient was presented in early life with congenital lobar emphysema. To our knowledge, it was the first instance of a defined respiratory problem described. In addition, the patient also had Morgagni hernia, which was another new finding in this syndrome. Short stature is a cardinal feature of MGS, observed in children and in adults. Few studies have documented variable results of endocrine work-up, including growth hormone assays. Loeys et al. [1999] reported two brothers with MGS, delayed bone age, one of whom was subjected to glucagon stimulation test with subnormal GH and borderline Somatomedin C. Cohen et al. [2002] reported on an 18.5-year-old patient that had severe proportionate short stature, and received recombinant GH therapy, though he has normal GH assay. They concluded that short stature was probably not related to growth hormone deficiency. Terhal et al. [2000] reported on two unrelated adolescent girls with MGS and both had breast hypoplasia, with regular menstrual periods. Endocrine work-up was entirely normal. In our patient, the stimulation test showed definite deficiency of GH while other endocrine work was normal. It is likely that the growth hormone deficiency is not the cause of short stature in MGS patients but possibly it contributes to the severity of growth deficiency later on in life and hence affects their ultimate height. Growth hormone supplementation was started, but it is too early to draw conclusions. We consider that it is important to regularly check growth hormone, including performing Clonidine stimulation tests in patients with MGS, on regular bases in the first years of life before puberty. To date, approximately 35 cases of this disorder have been published, from different ethnic groups. This patient is the first example of an Arab patient.
Two daughters of phenotypically normal parents are described with severe proportional dwarfism with microcephaly, peculiar craniofacial anomalies, microtia, absent patellae, joint hyperextensibility, and other anomalies. Intrafamilial variability is minimal. This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation. Autosomal recessive inheritance is strongly suggested by the presence of two pairs of affected siblings and the equal sex ratio.
Six children (5 male, 1 female) of normal first cousin Arab parents were found to have Silver-Russell syndrome. Manifestations included intrauterine and postnatal growth retardation, lateral asymmetry, relatively large head, small triangular face with prominent ears, clinodactyly of the fifth fingers, disproportionate toes, and normal psychomotor development. Intrafamilial variability was minimal. Parental consanguinity and affected siblings of both sexes strongly suggest autosomal recessive inheritance. Similar cases from literature are briefly reviewed.
Interstitial deletions involving 6q11-q14 have been reported in less than 20 patients, with the breakpoints studied by G-banding alone. We report on seven patients with 6q11-q14 interstitial deletions of variable size. The breakpoints were studied by G-banding, dual-color BAC-FISH and SNP array. The results showed the molecular breakpoints differed significantly from the ones obtained from G-banding. The breakpoints studied by BAC-FISH were consistent with the ones from SNP array. Some characteristics from this cohort are consistent with previous reports, but many typical features are lacking in our patients. The cardinal features of 6q11-q14 interstitial deletions in this cohort include: umbilical hernia, hypotonia, short stature, characteristic facial features of upslanting palpebral fissures, low set and/or dysplastic ears, high arched palate, urinary tract anomalies, and skeletal/limb anomalies.
We describe a 21-week-old fetus with a pattern of multiple congenital anomalies suggestive of the human homologue of the mouse mutant disorganization (Ds). Manifestations included facial asymmetry, thick eye brows, micrognathia, apparently lowset ears, an enormous abdominal wall defect, severe kyphoscoliosis, camptodactyly of the fingers, complete absence of the left lower limb, and absence of the lower part of the sacrum and coccyx, as well as left side of the pelvis. There was a disorganized appearance of the right foot with supernumerary digits and appendages and talipes equinovarus. No obvious amniotic bands or oligohydramnios were noted. Similar cases in the literature are reviewed and the clinical significance to genetic counselling is emphasized.
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