General Information

Around 1969, Dr. Meinhard Robinow identified a new medical syndrome, which he had not seen before. He named it "Fetal Face" Syndrome, based upon his views of patients born with the facial features of an 8-month old fetus. Some time later the name was changed to what we now know as "Robinow" Syndrome.

Before his death in July of 1997, he had observed, followed and studied a few families.

In 1995 the Robinow Syndrome Foundation was established, to continue locating and documenting new families addressing their individual characteristics, and to provide informational and emotional support.

Within this site you will find generalized information that has been compiled from Dr. Robinow’s findings and summarized, by parents, (noting that we are not in the medical profession and that this is our viewpoints and understandings of this syndrome), for parents - or those affected by Robinow Syndrome.

Two types of this syndrome have been described (Dominant & Recessive) and the following information refers to both of them. The patients usually have most of these signs in a minor to moderate scale.

1. Medical Manifestations:

A. Skeletal System

i. Mild to moderate short stature (dwarfism)

ii. Short lower arms (mesomelic brachymelia)

iii. Small hands with clinodactyly usually of the fifth finger (abnormal lateral or medial bending of one or more fingers or toes) and brachydactyly (abnormally short fingers or toes)

iv. Small feet

B. Spinal Malformations

i. Vertebral segmentation defects

ii. Dominant - at most a single butterfly vertebra

iii. Recessive - multiple vertebral segmentation defects (often multiple rib anomalies, fusions).

iv. Hemivertebrae, vertebral fusions, narrow interpediculate distances most common in the recessive form.

v. Possible - spinal cord tethering

C. Abnormalities of the Head and Facial Area (craniofacial, fetal face)

i. Flat facial profile with larger head (MACROcephaly not necessarily associated with hydrocephaly) may present with pituitary gland abnormal function in few cases

ii. Prominant or bulging forehead with widely spaced eyes

iii. Short, upturned nose with anteverted nostrils and flat nasal bridge

iv. Wide triangular mouth; long philtrum with broad horizontal upper lip in the dominant form, short philtrum with an inverted V-shaped or tented upper lip in the recessive form

v. Crowded, misaligned teeth and gum hypertrophy

D. Eyes and Ears

i. Hypertelorism / Hypoplastic, or shortened, S-shaped lower eyelids giving the impression of prominent eyes

ii. Ears are sometimes cup-shaped, flapped and/or low-set

E. Genital Hypoplasia

i. Males often born with buried penis sometimes shortened phallus only visible when the surrounding skin is retracted

ii. Undescended testicles, hypospadius may be present.

iii. In females, the clitoris and labia minora (sometimes labia majora) are underdeveloped (hypoplastic).

F. Gynecology

i. Vaginal atresia - two recessive cases known

ii. Bicornuate Uterus - one known case - recessive

2. Types:

A. Dominant (most common)

i. The parents are usually not carriers of the dominant gene that produces the syndrome

ii. Patients with the dominant version have most of the medical manifestations listed in a minor to moderate scale

B. Recessive (the rarer of the two)

i. Both parents carry the recessive gene and have a 25% chance of producing an affected offspring

ii. Children born with the recessive version have more marked dwarfism, radial head dislocation, shorter limbs, shorter fingers and toes and spinal segmentation defects. Recessive cases appear to have more of the skeletal abnormalities

3. Other:

A. Urinary

i. Micropenis

ii. Hydronephrosis, urinary tract infections

B. Growth and Development

i. Intelligence is normal in most cases, mildly impaired in some. Psychosocial problems related to appearance are an issue.

ii. Normal to borderline adult height in dominant forms. Recessive forms will have more marked dwarfism.

C. Procreation / Inheritance

Fertility and reproduction have been documented in females with both forms of the syndrome. Males with the dominant form have produced offspring. Procreation in males with the recessive type has not yet been documented.

D. Scoliosis

Scoliosis is progressive and should be monitored for treatment.

E. Rarity

Very rare - 1/100,000 (six known recessive in usa ). However, some in Czechoslovakia report that the condition is not rare among the gypsy population and there are reports of the condition in other countries as well. (Recessive is rare in the US, but, reports from Egypt and Turkey have more frequent recessive cases in offspring from first cousin marriages).

F. Correct Diagnosis

Diagnosis is difficult because Robinow Syndrome presents differently in each person afflicted. Therefore, to
differentiate it from other syndromes (Aarskog, Hurler, and other types of micropenis, achondroplasia,
and pseudohypoparathyroidism), radiological exams are necessary to provide confirmation of the skeletal malformations. Radiological findings, when associated with the other manifestations listed above, create a combination so striking and characteristic that no other condition with severe facial and acral involvement need be considered.

The recessive and dominant forms can be diagnosed clinically and blood tests to check for mutations are available.

The following is taken mostly from the summary of clinical features in Robinow Syndrome

GESTATION AND FAMILY HISTORY

Normal pregnancy

Normal birth weight

INHERITANCE

The recessive form is caused by mutation in ROR2 gene. This gene is located in chromosome 9q22 and works in cartilage and bone formation. In this type both parents are carriers of a recessive gene and are not affected. This couple have a 25% risk of having another child affected by the syndrome. (Figure 1).

The genes responsible for the dominant form are DVL1 and DVL3 and WNT5A. The dominant form is usually caused by new mutations with a small risk for another pregnancy. In some cases it can be inherited from one of the parents that can be affected or not or probably so mildly affected that they cannot be diagnosed. In this case, there is a 50% risk for another child being affected, of this parent.

CRANIO-FACIAL

Hypertelorism (wide apart eyes)

Short upturned nose

Broad nasal bridge (wide, flat nose)

Anteverted mares (upturned nose)

Triangular mouth (bottom corners face downward)

Frontal Bossing (boxlike forehead)

Long / short philtrum (upper lip)

Micrognathia (small chin)

Wide palpebral fissures (wide eye openings)

Downslanting palpebral fissures (slanted eyes)

Ear abnormality (small and lower set)

Facial nevus (birthmark on face)

Normal Intelligence

ORAL

Dental abnormalities / malaligned teeth (crowded, crooked, missing teeth)

Gingival hyperplasia (thick gums)

Abnormal uvula (heart shaped)

Cleft lip / palate (non-midline)

Shortened tongue / some with midline indentation

MUSCULO-SKELETAL

Short stature (height)

Vertebral anomalies (segmentation defects)

Scoliosis (curvature of the spine)

Rib defects (fused ribs)

Delayed bone age

Inguinal or umbilical hernias (groin & bellybutton)

Pectus excavatum (indentation in center of chest)

Elbow dislocations (lack of supination in forearms/wrists.)

Hip dislocation (hyper-extension)

EXTREMITIES

Mesomelic brachymelia (short forearms & legs)

Small hands with clinodactyly - Permanent deflection (curving/moving to one side) of one or more fingers.

Nail dysplasia (under - and faulty development of nail)

Subluxation of elbows (dislocation)

Webbed fingers/toes

Broad or Bifid Thumb (Congenital malformed thumb where the distal phalanx is divided)

Club feet

Ankle valgus deformity

Fibular hypoplasia

URO-GENITAL

Hypoplastic genitalia (decreased in size)

Cryptorchism (failure of one or both of the testis to descend)

Renal abnormalities, reflux (kidney)

Hypospadius (urethra opening on underside - mild to severe)

SEGREGATION OF AUTOSOMAL RECESSIVE TRAIT
(Both parents are carriers)

MEDICAL ISSUES

Frequent ear infections / hearing loss

Hypotonia

May be at risk for developmental delays

Breathing/respiratory problems

Feeding/eating difficulties

Photophobia (light sensitivity)

Esophageal reflux

Growth hormone deficiency - two known cases - recessive

REFERENCES

Afzal A.R., Rajab A., Fenske C., Crosby A., Lahiri N., Ternes-Pereira E., Murday V.A., Houlston (2000)

Linkage of recessive Robinow syndrome to a 4 cM interval on chromosome 9q22. Human Genetics 106: 351-354

Afzal AR., Rajab A., Fenske C., Oldridge M., Elanko N., Ternes-Pereira E., Tüysuz B., Murday V.A., Patton M.A., Wilkie A.O.M., Jeffery S. (2000)

Recessive Robinow syndrome: allelic to dominant brachydactily type B is caused by mutations of ROR2. Nature Genetics 25: 419-422

Butler N., Wadlington W.B. (1987)
Robinow syndrome: report of two patients and review of literature. Clinical Genetics 31: 77-85

Patton M.A., Afzal A.R. (2002)
Robinow syndrome (review) J Med Genet 39(5): 305-310

Robinow M., Silverman F.N., Smith H.D. (1969)
A newly recognized dwarfing syndrome. Amer. J. Dis. Child 117: 645-651

Van Bokhoven H., Celli J., Kayserili H., Van Beusekom E., Balci S., Brussel W., Skovby F., Kerr B., Percin E.F., Akarsu N., Brunner H.G. (2000):

Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome. Nature Genetics 25: 423-426

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