Robinow Syndrome, Autosomal Recessive

Alternative Names

  • RRS
  • Costovertebral Segmentation Defect with Mesomelia
  • Covesdem Syndrome
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WHO-ICD-10 version:2010

Diseases of the musculoskeletal system and connective tissue

OMIM Number

268310

Mode of Inheritance

Autosomal recessive

Gene Map Locus

9q22.31

Description

Autosomal Recessive Robinow Syndrome is a rare genetic disorder characterised by abnormalities of the skeletal system, head, face and external genitalia. Affected individuals have shortened bones in the arms and legs, wedge shaped vertebrae, curved spine and short stature. Dysmorphic facial features, underdeveloped genitalia and oral anomalies are also observed in patients. Phenotypic presentation in patients with Robinow Syndrome is related to the inheritance pattern and those with the recessive form have more severe symptoms; the main discriminating feature being the occurrence of multiple rib and vertebral anomalies. Pulmonary or cardiac complications are also common in affected individuals. Intelligence is normal in most cases although some degree of mental retardation occurs in few (20%). While the incidence of Robinow syndrome is about 1:500,000, the prevalence is slightly lower since 5-10% of patients die in infancy or early childhood.

Homozygous loss-of-function mutations in the gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2), located on chromosome 9q22.31, are responsible for autosomal recessive Robinow syndrome. ROR2 gene encodes a homodimer protein that is expressed at high levels during early embryonic development, which promotes osteogenesis and is considered to be essential for cartilage and growth plate development.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
268310.1.1LebanonFemaleYesYes Short stature; Macrocephaly; Prominent... NM_004560.3:c.814C>THomozygousAutosomal, RecessiveMehawej et al., 2012 Patient 1
268310.1.2LebanonFemaleYesYes Short stature; Macrocephaly; Prominent... NM_004560.3:c.814C>THomozygousAutosomal, RecessiveMehawej et al., 2012 Patient 2, sister of...

Other Reports

Egypt

[See: Oman > Soliman et al., 1998].

Kuwait

Teebi (1990) reported two brothers, born to first-cousin parents, with Robinow syndrome. Their paternal uncle also married a first cousin and had three similarly affected children (2 boys, 1 girl). The two affected brothers had short stature, mesomelic and acromelic brachymelia, characteristic face with hypertelorism, wide palpebral fissures, midface hypoplasia and large mouth, and hypogenitalism. Parental consanguinity and the presence of affected individuals in two sibships of common ancestry strongly suggested autosomal recessive inheritance. In 1991, Robinow also had reports of recessive cases from Kuwait (Source: OMIM).

Sabry et al. (1997) reported a child from a Kuwaiti consanguineous family with Robinow syndrome. The index case showed some unusual features including severe associated intrauterine growth retardation (IUGR), laxity of ligaments, hyperextensible joints, redundant skin folds, severe normocytic anemia, and repeated infection associated with increased total T cells and an increased CD4:CD8 ratio.

Oman

Soliman et al. (1998) conducted a study on 14 patients from six consanguineous Omani families with the recessive form of Robinow syndrome to analyze their growth patterns and the growth hormone (GH) response to provocation with clonidine and the serum insulin-like growth factor-I (IGF-I) concentration in 12 of these children. A set of 12 normal children with constitutional growth delay were used as a control group for gonadotrophin releasing hormone (GnRH) and human chorionic gonadotrophin (HCG) tests. Children with Robinow syndrome, born at full-term, were short at birth (length, 41.4+/-2.1 cm) and had markedly slow growth velocity (GV) during the first year (13.1+/-2.1 cm/yr); consequently, they were significantly short at the end of the first year of life (length, 54.4+/-2.9 cm). This intrauterine and early extrauterine growth delay reflected low growth potential. During childhood and early adolescence, boys with Robinow syndrome had low basal testosterone and a low testosterone response to HCG stimulation (3,000 IU/m2/d intramuscularly [IM] for 3 days), although they had normal basal and GnRH-stimulated FSH (follicle-stimulating hormone) concentrations. On the other hand, two girls (Tanner II breast development) had a normal serum estradiol (E2) concentration but high LH and FSH responses to GnRH stimulation. This suggested either defective feedback of E2 on the hypothalamic-pituitary axis or hyporesponsiveness of the ovaries to gonadotropin. Three boys received HCG for four weeks and their penile length and testicular volume were increased, reflecting a significant Leydig cell response to prolonged HCG stimulation and the presence of functioning androgen receptors. Soliman et al (1998) suggested that severe micropenis in patients with Robinow syndrome might improve, if they receive HCG and/or testosterone during infancy.

Rajab et al. (2005) undertook a study to estimate the prevalence of commonly diagnosed autosomal recessive diseases in Oman from a hospital-based register in years 1993 to 2002. The study revealed that Robinow syndrome was diagnosed in 12 patients, with an observed incidence of 1 in 35,000 births.

Saudi Arabia

Nazer et al. (1990) reported two children, born to first-cousin Saudi parents, with the 'fetal face syndrome.' Both of the children also had the Crigler-Najjar syndrome, as did two previously born sibs who did not have the fetal face syndrome. Both died at age 4 months. The parents lost two previous children at age 2 months with progressive jaundice but without fetal facial characteristics. Robinow (1991) also had reports of recessive cases from Saudi Arabia (Source: OMIM).

United Arab Emirates

Al Talabani et al. (1998) in their study on the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital,  observed one case of autosomal recessive Robinow syndrome born to a first cousin couple from the United Arab Emirates. Recurrence was also reported in the family. 

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