Congenital limb defects in a married female population of the Rahim Yar Khan District in Pakistan.

Background: Congenital limb defects (CLD) have a range of phenotypes and can be a substantial cause of disability. The prevalence of CLD in the adult population of Pakistan is not well described. Objectives: To investigate the prevalence of CLD and their associated factors in a married female population of the Rahim Yar Khan (RYK) District in Pakistan. Methods: A cross-sectional population-based study was conducted in 4 tehsils of RYK District, and married women and girls from 22 different localities were enrolled by convenience sampling in public places and through door-to-door visits. Data regarding limb phenotype and demographic variables were obtained from participants. Results: We enrolled 2,204 married women and girls. We found 11 participants with CLD suggesting a prevalence of 4.99/1,000 (proportion: 0.005; 95% confidence interval [CI] <0.001-0.01). Polydactyly was the most frequent (n = 5; prevalence: 2.27/1,000), followed by others in the following sequence: brachydactyly (n = 4; prevalence: 1.81/1,000), camptodactyly (n = 1; prevalence: 0.45/1,000), and oligodactyly (n = 1; prevalence: 0.45/1,000). The odds of occurrence of CLD were higher in individuals originating from Khanpur tehsil (odds ratio [OR] 2.05; 95% CI 0.37-11.27), speaking languages other than Punjabi and Saraiki (OR 2.35; 95% CI 0.24-22.80), belonging to Araien caste (OR 2.35; 95% CI: 0.24-22.80), of a nuclear family (OR 3.35; 95% CI 0.79-16.97), or having parental consanguinity (OR 1.87; 95% CI 0.49-7.06). Conclusion: Preliminary estimate of CLD prevalence in the married female sample population in RYK appears high compared with estimates from birth defects registries in other countries.

Phenotypic manifestation of congenital transverse amputation of autopod in Pakistani subjects.

Terminal transverse deficiency of forearm is a very rare limb malformation. Most of the cases have traumatic etiology and congenital presentation is less common. A series of six individuals with transverse deficiency through the hands is presented in this communication. The cases were congenital, morphologically similar and showed loss of four fingers, most often postaxial. The affected arm was reduced in size compared to the contralateral limb and there was distortion of palmer creases. All cases were sporadic and non-syndromic in nature. The characteristics of these cases were concordant with the symbrachydactyly type III or monodactylous type, when classified according to the scheme proposed by Blauth and Gekeler (1973). The malformation resulted in permanent quality-of-life impairment in these subjects and warrant prosthetic management. Detailed physical and phenotypic features of the patients have been presented.

Consanguinity and its socio-biological parameters in Rahim Yar Khan District, Southern Punjab, Pakistan.

BACKGROUND: Rahim Yar Khan (RYK) District is a multi-ethnic assemblage of both ancient and migrated communities in Southern Punjab, Pakistan. There is a paucity of knowledge on the bio-demographic structure of this endogamous population. METHODS: We have carried out a cross-sectional epidemiological study in RYK District and recruited 2174 random Muslim married females. Detailed account of marital union types, level of consanguinity, and subject's fertility, was taken. RESULTS: The analyses of these data revealed that consanguineous unions (CU) were 58.46 %, rendering an inbreeding coefficient (IC-F) = 0.0355. The CU were observed to be significantly higher in subjects originating from rural areas, speaking Saraiki language, illiterate or having a religious/Madarsa education only, and belonging to nuclear family type. The rate of consanguinity was also higher in subjects whose husbands were engaged in unskilled manual or skilled manual jobs, and had consanguinity in the parental generation. Multivariate logistic regression analyses revealed that variables like Saraiki language, illiteracy, reciprocal marriages, and parental consanguinity, were the significant predictors of CU in the subject. Among the first cousin unions (which constituted 52 % of all marriages), parallel-cousin and patrilineal unions were in the majority (54 and 57 %, respectively), and father's brother's daughter type had the highest representation (31 %). The analyses further demonstrated that fertility and mean live-births were significantly higher in women who had CU compared to the non-consanguineous (NCU) group (p < 0.006); and significantly higher number of sons per women were born to the mothers who had CU compared with the NCU sample (p = 0.0002). However, there were no differences in the CU and NCU samples with respect to pre- or post-natal mortalities and child morbidities. CONCLUSIONS: The scientific findings in RYK District are distinct from the observations in other Pakistani populations and clue to a unique nature of this population. This study presents a comprehensive account of consanguinity and IC-F in RYK District and would be helpful in getting an insight into the structure of this population.

Recurrent mutation in CDMP1 in a family with Grebe chondrodysplasia: broadening the phenotypic manifestation of syndrome in Pakistani population.

Grebe syndrome (OMIM-200700) is a very rare type of acromesomelic dysplasia with autosomal recessive inheritance. We studied a Pakistani family with two affected individuals having typical features of Grebe chondrodysplasia. Patients were observed with short and deformed limbs having a proximo-distal gradient of severity. Hind-limbs were more severely affected than fore-limbs. Digits on autopods were very short and nonfunctional. Index subject also had nearsightedness. However, symptoms in the craniofacial and axial skeleton were minimal. Genetic analysis revealed four base pair insertion mutation (c.1114insGAGT) in gene coding cartilage-derived morphogenetic protein-1 (CDMP1). This mutation was predicted to cause premature stop codon. The clinical presentation in this study broadens the range of phenotypes associated with CDMP1 mutation in Pakistani population.

Study of non-syndromic thumb aplasia in six independent cases.

OBJECTIVES: To report on six independent and isolated cases demonstrating thumb aplasia as an essentially limb-specific phenotype. METHODS: The subjects were ascertained during 2011-2013 from six different geographic regions of Pakistan, and underwent detailed clinical and phenotypic examination. RESULTS: The affected arms of patients had complete absence of first digital rays, medial inclinations of second and fifth fingers, narrowing of palms, missing carpals, and shortening of zeugopod. All the subjects were presented with isolated and sporadic limb deficiencies, and five had no family history of limb or any other malformation. Parental consanguinity was denied in majority of the cases. We present detailed phenotypic manifestation of thumb apalsia in these subjects. CONCLUSION: Thumb aplasia markedly impairs the normal function of affected hand. Surgical procedures like pollicisation of the index finger should be employed to improve the quality of life of these subjects. There is so far no specific genetic factor known for isolated thumb aplasia, compromising an accurate genetic counseling. Collection of patients with similar phenotypic presentations could be useful in further molecular genetic investigations.