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Renpenning syndrome is an X-linked intellectual disability syndrome (XLMR, see this term) characterized by intellectual deficiency, microcephaly, leanness and mild short stature.
ORPHA:3242Classification level: Disorder
Prevalence is unknown.
The main clinical manifestations of Renpenning syndrome are usually moderate intellectual deficiency, leanness, microcephaly and short stature (relative to familial target measurements) and sometimes small testes (testicular volumes below 15 ml), that are noticed at puberty. Manifestations are expressed only in males, and female carriers show normal facial features, growth development and intelligence. Small head and brain sizes are noted at birth. Characteristic craniofacial features include long triangular faces with upslanting palpebral fissures, half-depilated eyebrows, large ridged or bulbous nose with overhanging columella, short philtrum, and cupped and laterally protruding ears. Patients are thin and show failure to thrive. Delayed motor and language development is noticed in children from an early age. Moderate to severe intellectual deficiency is seen in two thirds of cases. Muscular atrophy is also observed affecting mostly the spine and back muscles resulting in fall of head, upper back curve loss and an appearance of scapula alata. Metacarpophalangeal ankylosis of the thumb and muscular atrophy of the intrinsic muscles of the hand can occur in some cases. Although uncommon, cardiac malformations (atrial septal defect), cleft palate, ocular colobomas and imperforate anus have been noted in a few patients. Phenotypic variants grouped under Renpenning syndrome include Golabi-Ito-Hall syndrome, Hamel cerebro-palato-cardiac syndrome (see these terms), Porteous syndrome, Sutherland-Haan syndrome, MRX55 and three other XLMR families. Hamel cerebro-palato-cardiac syndrome usually has the most severe manifestations.
Renpenning syndrome is an X-linked condition caused by mutations in the polyglutamine tract-binding protein 1 (PQBP1) gene, encoding a nuclear protein that regulates pre-mRNA splicing and transcription. Six of the seven mutations discovered in the PQBP1 gene result in a truncated protein whereas a missense mutation that does not affect the length of the mutated protein is seen in Golabi-Ito-Hall syndrome.
Diagnosis is based on inheritance of clinical manifestations of Renpenning syndrome. It is often difficult if there is only one male with intellectual deficiency in a family, but it must be suggested even in sporadic cases. Brain magnetic resonance imaging (MRI) shows no obvious gyral reduction, which contrasts with frank microcephaly. PQBP1 gene screening for a mutation can confirm diagnosis.
Fragile X syndrome is a differential diagnosis but microcephaly is not a feature. Other causes of microcephaly such as fetal CMV infection, fetal alcohol syndrome, maternal phenylketonuria, autosomal recessive microcephalies and Smith-Lemli-Opitz syndrome (see this term) should be considered.
If a mutation is identified, prenatal diagnosis may be proposed to parents for further pregnancies. In sporadic cases, germinal mosaicism should be ruled out on prenatal setting.
Renpenning syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring.
Management and treatment
Management for Renpenning syndrome involves early education and intervention by trained therapists and treatment of any associated symptoms (cardiac defect, hypospadias, conductive deafness, strabismus). Children need to attend special education courses at school due to learning disabilities.
There is no cure for Renpenning syndrome but in most cases there is no decrease in life expectancy.
A summary on this disease is available in Deutsch (2012) Español (2012) Français (2012) Italiano (2012) Nederlands (2012) Português (2012) Polski (2012, pdf) Polski (2012)