Ulna and Fibula, Absence of, with Severe Limb Deficiency

Alternative Names

  • Limb/Pelvis-Hypoplasia/Aplasia Syndrome
  • LPHAS
  • Al-Awadi/Raas-Rothschild Syndrome
  • AARRS
  • Schinzel Phocomelia Syndrome
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations and deformations of the musculoskeletal system

OMIM Number

276820

Mode of Inheritance

Autosomal recessive

Gene Map Locus

3p25

Description

Limb/Pelvis-Hypoplasia/Aplasia syndrome (LPHAS) is a rare autosomal recessive disorder, characterized by a profound deficiency of the limbs, absent or hypoplastic pelvic bones, skull defects, thoracic dystrophy, unusual facies, and genital malformations. Pelvic bones show sacral agenesis or hypoplasia, whereas the skull might show a defect of the occipital bone with or without meningocele. Characteristic facial features include dysplastic and large ears, high and narrow palate, broad nasal bridge and nose, and a broad neck. Genital malformations include Mullerian aplasia, and agenesis of the uterus and vagina in females, and micropenis with cryptorchidism in males. Affected patients display normal growth and intelligence.

Most patients reported with LPHAS have been born to consanguineous parents, suggesting an autosomal recessive mode of inheritance. Linkage studies identified mutations in the WNT7A (Wingless Type MMTV Integration Site Family Member 7A) gene to be the cause of the disease. The protein product of this gene plays a major role in several developmental processes, including dorso-ventral patterning, and development of the anterior-posterior axis in the female reproductive tract.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
276820.1.1SyriaMaleYesYes Aplasia/Hypoplasia of the fibula; Apla...NM_004625.4:c.874C>THomozygousAutosomal, RecessiveWoods et al. 2006
276820.1.2SyriaFemaleYesYes Aplasia/Hypoplasia of the fibula; Apla...NM_004625.4:c.874C>THomozygousAutosomal, RecessiveWoods et al. 2006 Sibling of 276820.1....
276820.2Saudi ArabiaFemaleYes Aplasia/Hypoplasia of the nails; Hypopla...NM_004625.4:c.610G>AHomozygousAutosomal, RecessiveBalwi, 2009; Maddirevula et al. 2018
276820.3Saudi ArabiaMaleNoYes Aplasia/hypoplasia of the extremities; B...NM_004625.4:c.610G>AHomozygousAutosomal, RecessiveAl-Qattan et al. 2009
276820.4.1Saudi ArabiaFemaleYesYes Aplasia/hypoplasia of the extremities; A...NM_004625.4:c.610G>AHomozygousAutosomal, RecessiveEyaid et al. 2011 Proband from the lar...
276820.4.2Saudi ArabiaFemaleYesYes Aplasia/hypoplasia of the extremities; A...NM_004625.4:c.610G>AHomozygousAutosomal, RecessiveEyaid et al. 2011 Relative of 276821.4...
276820.4.3Saudi ArabiaMaleYesYes Amelia involving the upper limbs; Abnorm...NM_004625.4:c.610G>AHomozygousAutosomal, RecessiveEyaid et al. 2011 Brother of 276821.4....

Other Reports

Jordan

Al-Awadi et al. (1985) were the first to report a case of this condition. The patients they reported on were two siblings, born to healthy consanguineous parents from Jordan. The older patient, a 12-year old girl, presented with an elongated face, a right epicanthic fold, broad nasal bridge and nose, a broad neck, a barrel shaped chest with prominent sternum, lack of elbows with contraction deformity, short forearms, four digits in each hand, vestigial nails, and missing fifth ulnar ray with fusion of some of the carpal bones. She had gross pelvic malformation with very short appendages made up of one lower limb bone with a detached head and neck of femur. Her lower limbs were useless. Her 10-year old brother showed a similar phenotype. His external genitalia were anteverted, and he had inguinal testes a deep anal pit, and no gluteal cleft. Both patients had normal intelligence. Three other siblings were phenotypically normal. There was no other family history for such a condition. Later, Teebi (1993) further reported on the re-evaluation of the female patient. By this time, she was 18-years old, and had not attained menarche, although secondary sexual characters had developed. Her FSH, LH, and prolactin levels were found to be normal. Abdomenal ultrasonography revealed normal ovaries, but an absent uterus.

Kuwait

Farag et al. (1993) described a Bedouin girl, born to consanguineous parents belonging to a highly inbred tribe. The neonate had normal anthropometric measurements, except for a short length, which was due to profound limb hypoplasia and aplasia, especially of the lower limbs. The upper limbs showed contracture deformities, brachymesomelia, absent ulna, angulated radii, and postaxial oligodactyly. She had flask shaped thighs, phocomelia, and hypoplastic feet. The external genitalia were displaced anteriorly. X-ray studies showed short ulna, angulated radii, oligodactyly with absent rays in the upper limbs, and proximal hip dislocation, bifurcated femora, absent tibia and fibula and some rays in the lower limbs. Pelvic ultrasonography revealed an absent uterus, indicating Mullerian aplasia. The patient had a normal karyotype. The patient showed no developmental retardation at a later assessment.

Al-Naggar et al. (2004) described three Kuwaiti patients with LPHAS (two males, one female) from two families. The affected patients had intercalary and distal limb reduction malformations, hypoplastic pelvic bones, and unusual facies. Two of them showed capillary hemangiomata, sparse hair, short nose, dysplastic ears, and retrognathia. One of the patients had a balanced, reciprocal translocation, t(1,3)(q32:q21). The remaining two had normal karyotypes. [Al-Naggar RL, Al-Awadi SA, Hanafi EM, Al-Adwani A, Al-Daboos RM, Abu-Alhassan SJ, Murthy K, Marafi MJ, Bastaki LA. Limb/pelvis hypoplasia/aplasia (Al-Awadi/RaasRothschild) syndrome in three new Kuwaiti patients: clinical and radiological description. Egypt J Med Hum Genet. 2004; 5(1):59-68.]

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