Disease characteristics. Baller-Gerold syndrome (BGS) is characterized by coronal craniosynostosis, manifest as abnormal shape of the skull (brachycephaly) with ocular proptosis and bulging forehead; radial ray defect, manifest as oligodactyly (reduction in number of digits), aplasia or hypoplasia of the thumb, and/or aplasia or hypoplasia of the radius; growth retardation and poikiloderma. Findings in individuals with BGS overlap with those of Rothmund-Thomson syndrome (RTS) and RAPADILINO syndrome, also caused by mutations in RECQL4. RTS is characterized by poikiloderma; sparse hair, eyelashes, and/or eyebrows/lashes; small stature; skeletal and dental abnormalities; cataracts; and an increased risk for cancer, especially osteosarcoma. RAPADILINO syndrome is an acronym for radial ray defect; patellae hypoplasia or aplasia and cleft or highly arched palate; diarrhea and dislocated joints; little size and limb malformation; nose slender and normal intelligence.
Diagnosis/testing. The diagnosis of BGS is based on clinical findings. RECQL4 is the only gene currently known to be associated with BGS. Sequence analysis of the exons and the short introns of RECQL4 has detected mutations in 100% of the limited number of persons with BGS tested to date.
Management. Treatment of manifestations: surgery before age six months to repair bilateral craniosynostosis; pollicization of the index finger as needed to create a functional grasp. Surveillance: for persons with deleterious RECQL4 mutations that correlate with an increased risk for osteosarcoma, attention to clinical findings such as bone pain, limp, and fracture. Agents/circumstances to avoid: sun exposure because of risk for skin cancer.
Genetic counseling. Baller-Gerold syndrome is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk is possible if both disease-causing alleles in the family have been identified.
The diagnosis of Baller-Gerold syndrome (BGS) rests on the following findings:
Coronal craniosynostosis, manifest clinically as abnormal shape of the skull (brachycephaly) with ocular proptosis and bulging forehead. The diagnosis needs to be confirmed by skull x-ray or preferably by 3D-CT reconstruction. When the coronal sutures are fused, the orbit is pulled back and forward. The coronal sutures cannot be discerned on the frontal view, and the same holds true for the lambdoidal sutures.
Radial ray defect, manifest as oligodactyly (reduction in number of digits), aplasia or hypoplasia of the thumb, and/or aplasia or hypoplasia of the radius.
Note: Radiographs may be necessary for confirmation of minor radial ray malformations.
Growth retardation and poikiloderma (not in early infancy), although not diagnostic per se, may help establishing the diagnosis.
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Gene. RECQL4 is the only gene currently known to be associated with BGS [Van Maldergem et al 2006].
Other loci. No other loci for BGS are known or suspected. However, some cases provisionally assigned to the BGS clinical spectrum were reassigned to other nosologic entities such as Saethre-Chotzen syndrome, Roberts-SC syndrome, or Fanconi anemia [Huson et al 1990, Farrell et al 1994, Preis et al 1995, Cohen & Toriello 1996, Rossbach et al 1996, Quarrell et al 1998, Gripp et al 1999, Megarbané et al 2000, Seto et al 2001].
Clinical testing
Sequence analysis of the entire gene including exons and the short introns [Wang et al 2002] detects mutations in 100% of persons with BGS; however, this detection rate is based on results from fewer than ten families.
Table 1 summarizes molecular genetic testing for this disorder.
Test Method | Mutations Detected | Mutation Detection Frequency 1, 2 | Test Availability |
---|---|---|---|
Sequence analysis | RECQL4 sequence variants | Unknown | Clinical |
Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.
Confirmation of the diagnosis in a proband with clinical and radiographic evidence of coronal synostosis and radial ray defect requires molecular genetic testing to identify two disease-causing mutations in RECQL4.
Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.
Note: Carriers are heterozygotes for an autosomal recessive disorder and are not at risk of developing the disorder.
Prenatal diagnosis and preimplantation genetic diagnosis for at-risk pregnancies both require prior identification of the disease-causing mutations in the family.
Disease-causing mutations in RECQL4 have also been identified in individuals with Rothmund-Thomson syndrome [Kitao et al 1999] and RAPADILINO syndrome [Siitonen et al 2003].
Rothmund-Thomson syndrome (RTS) is characterized by skin changes termed poikiloderma; sparse hair, eyelashes, and/or eyebrows/lashes; small stature; skeletal and dental abnormalities; cataracts; and an increased risk for cancer. The skin is typically normal at birth; the skin changes of RTS begin between ages three and six months as erythema on the cheeks, which subsequently involves extremities with or without involvement of the buttocks. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, punctate atrophy, and telangiectases, collectively known as poikiloderma. Skeletal abnormalities include dysplasias, osteopenia, and absent or malformed bones (including absent radii). Osteosarcoma with a median age at diagnosis of 11 years occurred in 30% of a contemporary cohort. The prevalence of skin cancers, including basal cell carcinoma and squamous cell carcinoma, is estimated to be 5% [Wang et al 2003].
The diagnosis of RTS is usually made on the basis of clinical findings. Molecular testing is confirmatory and may be useful in situations in which clinical findings are atypical. Sequence analysis of RECQL4, the only gene known to be associated with RTS, detects mutations in about 66% of affected individuals. Inheritance is autosomal recessive.
RAPADILINO syndrome is an acronym for radial ray defect; patellae hypoplasia or aplasia and cleft or highly arched palate; diarrhea and dislocated joints; little size and limb malformation; nose slender and normal intelligence. It is characterized by pre- and postnatal growth retardation. Cervical spine segmentation defects have been reported. Failure to thrive results from feeding problems and juvenile diarrhea of unknown cause [Siitonen et al 2003]. Since its original description in Finland [Kaariainen et al 1989], only 14 Finnish and two non-Finnish individuals have been reported [Vargas et al 1992, Kant et al 1998, Jam et al 1999, Siitonen et al 2003]. Osteosarcoma was reported in one of the 16 individuals.
The Finn-specific RECQL4 splice-site mutation (IVS7+2delT) associated with RAPADILINO syndrome leads to in-frame skipping of exon 7 that is predicted to remove 44 amino acids just before the conserved helicase domain, apparently without altering transcription of the helicase domain itself. Nine of the 14 affected Finnish individuals are homozygous for IVS7+2delT and five are compound heterozygotes for IVS7+2delT and a nonsense mutation in extra-helicase exons 5, 18, and 19, thus sparing in all cases the helicase domain, which is therefore thought to play a role in poikiloderma and predisposition to osteosarcoma [Siitonen et al 2003].
RTS, RAPADILINO syndrome, and BGS share the clinical features of pre- and postnatal growth retardation, chronic diarrhea, and patellar hypo- or aplasia. Radial hypo- or aplasia is always seen in individuals with RAPADILINO syndrome and BGS and occasionally seen in those with RTS. Poikiloderma, a characteristic of both BGS and RTS, is not seen in RAPADILINO syndrome. However, the absence of poikiloderma cannot be confirmed before age one year because of its late onset. Coronal craniosynostosis, a diagnostic feature of BGS, has not been described in individuals with RTS. Alopecia and absence of eyelashes and brows, characteristics of RTS, are not seen in individuals with BGS.
Since the original description of Baller-Gerold syndrome (BGS) by Baller (1950) and Gerold (1959), a limited number of individuals with BGS have been reported [Greitzer et al 1974, Feingold et al 1979, Anyane-Yeboa et al 1980, Pelias et al 1981, Boudreaux et al 1990, Galea & Tolmie 1990, Lewis et al 1991, Dallapiccola et al 1992, Van Maldergem et al 1992, Lin et al 1993, Ramos Fuentes et al 1994, Franceschini et al 1998, Megarbané et al 2000].
At birth. Brachycephaly, shallow orbits, bulging forehead and megafontanelles, all manifestations of coronal synostosis, are always present at birth in individuals with BGS. Additional features such as saddle nose, nose hypoplasia, small mouth with thin vermilion border, and high arched palate, are part of the craniofacial phenotype.
A combination of oligodactyly, thumb hypo- or aplasia, and radial hypo- or aplasia is present and may be asymmetrical.
Patellar hypo- or aplasia is observed in childhood. Note: Late ossification of the patella may be misinterpreted as absence of the patella in infants.
Anterior displacement of the anus has been reported in several individuals.
Skin is normal.
In infancy. A few months after birth skin lesions may appear. Swelling of the extremities is seen first, followed by a peculiar mottled hypopigmentation (poikiloderma) on the arms, forearms, and legs. Blistering can develop on the face and then spread to the buttocks and extremities. After years, it becomes reticulated with hypo- and hyperpigmentation, punctate atrophy, and telangiectasias.
A hallmark is failure to thrive, with length decelerating to stabilize around -4 SD.
In childhood. Failure to thrive is the rule, with height and weight under 4 SD below the mean. Absence of patella may result in genu recurvatum and knee instability.
Intelligence is normal.
Genotype-phenotype information is provisional, owing to the limited number of individuals meeting the suggested diagnostic criteria for BGS.
In a series of 34 individuals with the allelic disorder RTS, osteosarcoma developed only in those with one or two truncating RECQL4 mutations, illustrating the importance of characterizing the disease-causing mutation(s) for cancer risk assessment [Wang et al 2001].
The name Baller-Gerold syndrome was coined by Cohen (1975) based on descriptions of three affected individuals reported by Baller and Gerold from the German literature.
Baller (1950) described a woman with short stature, oxycephaly, hypoplasia of the left radius, and aplasia of the right radius; her parents were remotely consanguineous.
Gerold (1959) described male and female sibs with coronal craniosynostosis, radial and thumb aplasia, and bowing of the ulnae.
Since 1975 the designation Baller-Gerold syndrome has been used to refer to any type of craniosynostosis associated with any type of radial ray defect; this is likely an incorrect use of the term, and has led some authors to consider metopic ridging and radial ray defects observed in valproate embryopathy sufficient for a diagnosis of BGS [Santos de Oliveira et al 2005].
The prevalence of Baller-Gerold syndrome is unknown; it is probably less than 1:1,000,000.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
The major differential diagnosis for Baller-Gerold syndrome (BGS) comprises the allelic disorders Rothmund-Thomson syndrome and RAPADILINO syndrome. (See Allelic Disorders.)
The second group of conditions to consider are those in which radial ray hypoplasia is a major component and craniosynostosis is occasionally described. This group includes the following:
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ear, heart, gastrointestinal system, oral cavity, and central nervous system; hearing loss; hypogonadism; and developmental delay. Craniosynostosis may occur. Progressive bone marrow failure with pancytopenia typically presents in the first decade. By age 40 to 48 years, the estimated cumulative incidence of bone marrow failure is 90%; of hematologic malignancies (primarily acute myeloid leukemia), 10%-33%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract), 28%-29%.
The diagnosis of FA rests upon the detection of chromosomal aberrations (breaks, rearrangements, radials, exchanges) in cells after culture with a DNA interstrand cross-linking agent such as diepoxybutane (DEB) or mitomycin C (MMC). Molecular genetic testing is complicated by the presence of at least 13 complementation groups [A, B, C, D1 (BRCA2), D2, E, F, G, I, J, L, M, N], for which at least eight genes have been identified. Inheritance is autosomal recessive.
Fetal valproate syndrome is the well-recognized association of reduction limb defects, radial hypo- or aplasia, trigonocephaly (resulting from metopic craniosynostosis), spina bifida, and other malformations (eye, palate, heart). The metopic ridging and radial ray defects observed in valproate embryopathy have been confused with BGS [Santos de Oliveira et al 2005].
VACTERL association includes vertebral anomalies, anal atresia, cardiac anomalies, tracheo-esophageal fistula, renal anomalies, and limb anomalies. The latter often comprises thumb hypo- or aplasia and in this respect may resemble BGS.
SALL4-related disorders include Duane-radial ray syndrome (DRRS, Okihiro syndrome) and acro-renal-ocular syndrome (AROS), two phenotypes previously thought to be distinct entities. DRRS is characterized by uni- or bilateral Duane anomaly and radial ray malformation that can include thenar hypoplasia and/or hypo- or aplasia of the thumbs; hypo- or aplasia of the radii; shortening and radial deviation of the forearms; triphalangeal thumbs; and duplication of the thumb (preaxial polydactyly). AROS is characterized by radial ray malformations, renal abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesico-ureteral reflux, bladder diverticula), ocular coloboma, and Duane anomaly. Additional features include sensorineural and/or conductive deafness. Diagnosis is based on clinical findings and detection of a SALL4 mutation. Inheritance is autosomal dominant [Kohlhase et al 2003].
Holt-Oram syndrome (HOS) is characterized by upper-extremity malformations involving radial, thenar, or carpal bones; congenital heart malformation, most commonly ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD), especially those occurring in the muscular trabeculated septum; and/or cardiac conduction disease. Seventy-five percent of individuals with HOS have a congenital heart malformation. The diagnosis of HOS is based on established clinical criteria and can be confirmed through molecular genetic testing. More than 70% of individuals who meet strict diagnostic criteria have an identifiable mutation in the TBX5 gene. Inheritance is autosomal dominant.
Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and presence of the thumbs despite more or less severe shortening of the upper limbs. TAR syndrome can be differentiated from BGS by the presence of craniosynostosis in individuals with BGS and the presence of thumbs in those with TAR syndrome. In contrast, the thumbs can be absent in individuals with Fanconi anemia or Roberts SC-phocomelia syndrome.
Previously thought to be autosomal recessive, the mode of inheritance of TAR syndrome is complex, with a microdeletion in 1q21.1 being necessary but not sufficient to determine the phenotype [Klopocki et al 2007].
The third group of conditions to consider are those in which craniosynostosis is the major finding, but other features may suggest BGS.
Saethre-Chotzen syndrome is characterized by coronal synostosis (unilateral or bilateral), facial asymmetry (particularly in individuals with unicoronal synostosis), ptosis, and characteristic appearance of the ear (small pinna with a prominent crus). Syndactyly of digits two and three of the hand is variably present. Although mild-to-moderate developmental delay and mental retardation have been reported, normal intelligence is more common. Less common manifestations of Saethre-Chotzen syndrome include short stature, parietal foramina, vertebral fusions, radioulnar synostosis, cleft palate, maxillary hypoplasia, ocular hypertelorism, hallux valgus, duplicated distal hallucal phalanx, and congenital heart malformations. Mutations in TWIST are causative [Paznekas et al 1998]. On rare occasion the radius is hypoplastic. Inheritance is autosomal dominant.
To establish the extent of disease in an individual diagnosed with Baller-Gerold syndrome, occupational therapy assessment to evaluate hand and arm function is recommended.
When craniosynostosis is bilateral, surgery is usually peformed before age six months.
Pollicization of the index finger to restore a functional grasp has had satisfactory results in a number of persons with absence of the thumb [Foucher et al 2005]. However, many children with aplasia of the thumb can use their first and second digits for grasping without pollicization.
For persons with deleterious RECQL4 mutations that correlate with an increased risk for osteosarcoma, attention to clinical findings such as bone pain, limp, and fracture is warranted. Currently no data are available regarding the effictiveness of routine screening such as x-rays, MRI, and bone scan. Furthermore, the risk of added radiation exposure from diagnostic studies and the benefit of "early" detection of osteosarcoma are unknown.
Sun exposure is to be avoided because of predisposition to skin cancer.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
Genetics clinics are a source of information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
Support groups have been established for individuals and families to provide information, support, and contact with other affected individuals. The Resources section may include disease-specific and/or umbrella support organizations.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Baller-Gerold syndrome (BGS) is inherited in an autosomal recessive manner.
Parents of a proband
The parents of an affected child are obligate heterozygotes and therefore carry one mutant allele.
Heterozygotes (carriers) are asymptomatic.
Sibs of a proband
At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
Heterozygotes (carriers) are asymptomatic.
Offspring of a proband. The offspring of an individual with BGS are obligate heterozygotes (carriers) for a disease-causing mutation.
Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.
Carrier testing for at-risk family members is available on a clinical basis once the mutations have been identified in an affected family member.
Family planning. The optimal time for determination of genetic risk, clarification of genetic status, and discussion of the availability of prenatal testing is before pregnancy. It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are at risk of being carriers.
DNA banking. DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%. See DNA Banking for a list of laboratories offering this service.
Molecular genetic testing. Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. Both disease-causing alleles must be identified before prenatal testing can be performed.
Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.
Ultrasound examination. Serial ultrasound examination may identify limb shortening, radial hypo/aplasia and abnormal head shape (brachycephaly). Ultrasound examination revealing these findings at 14 weeks' gestation identified BGS in an at-risk fetus.
Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutations have been identified. For laboratories offering PGD, see .
Information in the Molecular Genetics tables is current as of initial posting or most recent update. —ED.
Gene Symbol | Chromosomal Locus | Protein Name |
---|---|---|
RECQL4 | 8q24.3 | ATP-dependent DNA helicase Q4 |
Data are compiled from the following standard references: Gene symbol from HUGO; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from Swiss-Prot.
Gene Symbol | Entrez Gene | HGMD |
---|---|---|
RECQL4 | 9401 (MIM No. 603780) | RECQL4 |
For a description of the genomic databases listed, click here.
Note: HGMD requires registration.
Processing of aberrant DNA structures that arise during DNA replication and repair is a major role of ATP-dependent DNA helicase Q4, the protein encoded by RECQL4 (see Normal gene product). Disruption of DNA replication fork progression by stable secondary structures (e.g., forked structures that mimic replication forks, synthetic 4-way junctions and D-loops, gapped DNA, RNA-DNA hybrids, triplex DNA and G-quadruplex DNA) is likely to impede replication fork progression resulting in arrest or collapse of the fork. This can have potentially mutagenic or even lethal consequences for the cell as it results in chromosome instability and, ultimately, cell death or cancer. Mutations in RECQL4 impair the processing of these aberrant structures. In this respect, ATP-dependent DNA helicase Q4 can be considered a caretaker of the genome [Wu & Hickson 2006].
Normal allelic variants: RECQL4 has 21 exons, spanning over 6.5 kb. The gene has a coding sequence consisting of 3,627 bases based on the open reading frame of the initial cDNA clone. RECQL4 is unique for having 13 introns and fewer than 100 bp, a feature predisposing to inefficient splicing [Wang et al 2002].
Pathologic allelic variants: Three mutations have been demonstrated in two families with Baller-Gerold syndrome (BGS): a homozygous splice site mutation (IVS17-2A>C) and compound heterozygosity for a missense mutation (p.Arg1021Trp) and a classic RTS frameshift mutation (g.2886delT). The missense mutation induces substitution of the hydrophilic amino acid arginine by the hydrophobic residue tryptophan.
Overall, approximately 30 different RECQL4 mutations resulting in absent or truncated protein have been published [Kitao et al 1999, Lindor et al 2000, Balraj et al 2002, Wang et al 2002, Beghini et al 2003, Siitonen et al 2003, Wang et al 2003, Kellermayer et al 2005, Broom et al 2006, Van Maldergem et al 2006, Sznajer et al 2007]. The helicase domain, located in exons 8-14, is frequently the site of truncating mutations, but mutations in the N-terminus have also been described.
Normal gene product: RECQL4 encodes ATP-dependent DNA helicase Q4, a protein of 1,208 amino acids that bears homology to a family of proteins known as RecQ helicases [Kitao et al 1998]. Helicases are enzymes involved in unwinding and remodeling of double-stranded nucleic acids into single strands. They are ATP-dependent enzymes. They have essential functions at various stages of DNA processing (replication, recombination, repair, transcription), but also translation, RNA processing, and chromosome segregation. Helicases therefore contribute to maintaining genomic integrity. They are classified into families according to their direction of translocation along nucleic acid substrates and by the presence and conservation of characteristic helicase domains and motifs [Singleton & Wigley 2002]. The RecQ helicases belong to superfamily 2 of helicases. The first RecQ helicase was identified more than 20 years ago in Escherichia coli [Nakayama et al 1984]. RecQ helicases have a role in the processing of aberrant DNA structure that arises during DNA replication and repair [Khakhar et al 2003].
Members of the RecQ family can be distinguished from other helicases by a conserved domain varying from 320 to 390 amino acids in length in the middle of the protein. This region contains seven helicase motifs characteristic of the DExH-box superfamily that are involved in the binding and hydrolysis of NTP and the separation of nucleic acid duplexes [van Brabant et al 2000, Nakayama 2002]. At the C-terminal region, two other conserved sequence elements are commonly found in RecQ helicases: the RecQ-C-terminal (RQC; also known as RecQ-Ct) and the helicase-and-RNase D C-terminal (HRDC) domains [Morozov et al 1997]. Although the RQC and HRDC domains are found in most RecQs, some family members miss one or both domains. This is the case with the protein encoded by human RECQL4, which lacks the RQC and HRDC domains. The RQC domain seems to be unique to RecQ helicases and probably has a role in mediating specific protein-protein interactions. At least five RECQL human orthologs are known: RECQL, RECQL4, RECQL5, BLM, and WRN. Mutations in BLM are associated with Bloom syndrome; mutations in WRN are associated with Werner syndrome; both are chromosome instability conditions inherited in an autosomal recessive manner. RECQL4 has been associated with Rothmund-Thomson syndrome, RAPADILINO syndrome, and Baller-Gerold syndrome. To date, no human disease is known to be associated with RECQL or RECQL5 protein deficiency.
Despite its sequence structure, ATP-dependent DNA helicase Q4 does not actually demonstrate helicase activity, unlike the proteins encoded by related genes BLM and WRN. For a review see Van Maldergem et al (2007).
Abnormal gene product: Unknown
GeneReviews provides information about selected national organizations and resources for the benefit of the reader. GeneReviews is not responsible for information provided by other organizations. Information that appears in the Resources section of a GeneReview is current as of initial posting or most recent update of the GeneReview. Search GeneTests for this disorder and select for the most up-to-date Resources information.—ED.
Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas TX 75240
Phone: 800-535-3643; 214-570-9099
Fax: 214-570-8811
Email: contactCCA@ccakids.com
www.ccakids.com
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga TN 37401
Phone: 800-332-2373; 423-266-1632
Email: faces@faces-cranio.org
www.faces-cranio.org
National Institute of Neurological Disorders and Stroke
Craniosynostosis Information Page
Reach: The Association for children with Hand or Arm Deficiency
PO Box 54
Helston
Cornwall TR13 8WD
United Kingdom
Phone: 44 0845 1306 225
Fax: 44 0845 1300 262
Email: reach@reach.org.uk
www.reach.org.uk
Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page.
No specific guidelines regarding genetic testing for this disorder have been developed.
13 August 2007 (me) Review posted to live Web site
23 April 2007 (lvm) Original submission