American Journal of Medical Genetics 26:551-555 (1987)

Mental Retardation, Deafness, Skeletal Abnormalities, and Coarse Face With Full Lips: Confirmation of the Fountain Syndrome

Jean-Pierre Fryns, Annemie Dereymaeker, Margot Hoefnagels, and Herman Van den Berghe

Division of Human Genetics, Department of Human Biology, University Hospital, Leuven, Belgium

We describe 3 moderately to severely mentally retarded males (2 brothers and 1 isolated patient) with congenital deafness due to an anatomical inner ear anomaly, the same manifestations that were present in the 4 sibs reported by Fountain [1974]: skeletal abnormalities with broad, stubby hands and feet and hyperky- phosis, and a peculiar “coarse” face with swelling of the subcutaneous tissue, particularly of cheeks and lips. According to the present observations early-onset, generalized seizures can be added to the symptom complex of this autosomal recessive trait.

Key words: autosomal recessive inheritance, skeletal abnormalities, generalized seizures

CLINICAL REPORTS Patients 1 and 2

Two brothers, V.P. and V.L., were seen first at the age of 16 and 13 years, respectively, and followed for 13 years. The parents were nonconsanguineous, healthy and normal, and family history was unremarkable. The third child of this family, a 21-year-old woman, is normal and was referred for genetic counseling because of the handicap of her 2 brothers.

The eldest brother, V.P., was born at term after a normal pregnancy. Birth- weight was 4,150 g. No neonatal complications were noted. At 3 months, the boy developed hypsarrhythmia and, despite ACTH treatment, the seizures were difficult to control. Later he developed grand ma1 epilepsy and focal seizures involving the left arm, which were medically well controlled with valproate. Deafness was noted at 15 months. In addition to deafness and mild mental retardation, he had a peculiar round and coarse face with mild swelling of the subcutaneous tissue, particularly of

Received for publication October 26, 1985; revision received August 2, 1986.

Address reprint request to Jean-Pierre Fryns, Centre for Human Genetics, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

0 1987 Alan R. Liss, Inc.

552 Fryns et a1

Fig. 1. a) Left hand (patient 1); b) right hand (patient 2). Fig. 2. Patient 1 (29 years).

cheeks and lips. Hands and feet were short and plump (Fig. la) with broad and short terminal phalanges. Now, at 29 years (Fig. 2), the height is 170 cm, weight 62 kg, and the head circumference 55 cm. There was no evidence for internal malformations. Ophthalmological examination was normal.

Results of biochemical and metabolic examination were normal, including calcium, phosphorous, creatine kinase, amino acid chromatography of serum and urine, and urinary excretion of mucopolysaccharides. Chromosomes were normal (46,XY confirmed with G- and R-banding). Audiometry showed profound sensori- neural deafness with rudimentary hearing at the lowest frequencies. Vestibular func- tion was normal. X-ray tomography of the pars petrosa of the temporal bones showed anomalies of the turns of the cochlea. Skull films (Fig. 3) showed marked thickness of calvaria. The broad and plump aspect of hands and feet was confirmed roentgen- ologically with thickened corticalis but without ossification anomalies.

The younger brother (V.L., Fig. 4a,b) had the same medical history as his elder brother. Pregnancy and delivery were also normal. Birthweight was 3,900 g. At the age of 3 months he developed infantile spasms, which later became generalized convulsions, alternating with petit mal absences and myoclonic jerks. Now, at 26 years, epileptic attacks still occur regularly despite valproate treatment. Psychomotor retardation was moderate to severe from the beginning. The boy started to walk at 18 months. At that time profound deafness was noticed. Presently, he is in an institution for the severely mentally retarded. Height is 172 cm, weight 64.5 kg, and OFC 55.5 cm. His face is long and coarse with large, open mouth, full everted lips, high palate, small teeth, and mandibular prognathism (the swelling of the subcutaneous facial tissues, especially of the lower lip) became even more evident between the age of 13 and 26 years. There was generalized hypotonia with thoracolumbar scoliosis; hands and feet were broad and plump (Fig. lb). Results of extensive biochemical and metabolic screening, as performed on his older brother, were normal. Audiometry confirmed the presence of profound sensorineural deafness. Vestibular function was normal. A skeletal survey showed the same finding of the skull and hands and feet that were present in his elder brother.

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Fig. 3. Roentgenogram of the skull of patient 1, with marked thickness of the calvaria (17 years).

Fig. 4. Patient 2 (26 years). a) Long and coarse face and swelling of the subcutaneous tissue, especially of the lower lip b) .

Tomography of the pars petrosa of the left temporal bone showed a congenital anomaly of the inner ear with replacement of the cochlear turus by a simple cavity. Ophthalmological examination was normal. Chromosomes were normal (46,XY, after G- and Q-banding); fra (X) screening was negative on 100 examined cells.

Dermatoglyphics revealed a TRC of 77 with 9 ulnar loops and 1 radial loop on the second finger of the right handiTriradial position was in t (9.3 % at the right hand and 9% at the left hand). The atd was 90°. On both hands there was an ulnar hypothenar crease.

554 Fryns et a1

Patient 3 W.V.L. (Fig. 5), a male, was the second born of 3 children. His 2 sisters are

mentally and physically normal. Both parents are healthy and unrelated. At the child’s birth, the father was 22 and the mother 21 years old. Pregnancy and delivery, at 36 weeks, were normal. Birthweight was 2,750 g. Psychomotor retardation was severe from the beginning. Short stubby hands and feet, and a round, plethoric face were noted at age 2 years. Examination at 4 years showed a severely retarded boy, unable to walk or to speak, with a length of 93 cm (< 3rd centile), a weight of 15.2 kg, and an OFC of 51.5 cm.

Results of extensive biochemical investigations including ionogram, lipidogram, creatin kinase, chromatography of amino acids and carbohydrates, urinary mucopo- lysaccharides, and calcium were normal. Electrocardiography, electromyography, electroencephalography, ophthalmological examination and peripheral nerve, and rectal biopsies were normal. At that age (4 years) deafness was suspected, and audiometry confirmed the presence of a complete bilateral sensorineural deafness. At 6 years the boy was admitted to an institution for the severely mentally retarded.

Now, at the age of 17 years, he was re-examined during a systematic genetic and diagnostic survey of the severely mentally retarded. In addition to the severe mental retardation and the profound deafness, clinical examination confirmed pres- ence of an edematous, somewhat coarse face with thick, everted lips, h l l cheeks, and depressed nasal bridge (Fig. 5). Hands were short and plump. Dermatoglyphics showed a TRC value of 174 with ulnar loops on the first fingers and whorls on fingers I1 to V. Triradius was in t (18.9% at the right hand and 23.9% at the left hand). The atd was 76O. X-ray examination confirmed the presence of broad, heavy phalanges and metacarpals with thick cortices but without ossification defect. Skull films were normal. The length was 143.5 cm [<3rd centile). Motor impairment was pro- nounced, and the boy barely walked without support.

Fig. 5 . Patient 3 (17 years).

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DISCUSSION

In 1974, Fountain reported mental retardation and deafness in 4 sibs (3 boys and one girl); 2 had generalized facial edema and pronounced swelling of the upper and lower lips. The third child, a boy, had a history of deafness and mental deficiency without swelling of the lips. In all 3 , skull films showed gross thickness of the calvaria. A fourth child of this family died in early infancy and, in addition to being deaf and mentally retarded, had spina bifida.

In the 2 brothers of the present report a similar pattern of abnormalities was found. Both were mentally retarded; the developmental delay was mild in the oldest and moderate to severe in the youngest. Deaf mutism was noted at the ages of 15 and 18 months respectively, with complete sensorineural deafness. Tomography of the inner ear showed anatomic anomalies of the turns of the cochlea in both boys. The facial changes were most prominent in the youngest brother; there was plethoric swelling of the face with “edematous” infiltration of the subcutaneous tissue, mostly of the lips and the cheeks. A skeletal survey showed marked thickness of the calvaria and confirmed the clinical impression of short, stubby hands on the x-ray films, with broad and short phalanges and metacarpals with thickened corticalis. In addition (and different from the sibs reported by Fountain), both brothers developed infantile generalized seizures, which were more severe in the youngest. This may have resulted in a more severe developmental retardation in the youngest. As commented by W.B. Reed in Fountain’s report, the edematous facial changes in these patients are similar to those seen in the Melkerson-Rosenthal (M-R) syndrome, an autosomal dominant condition often manifested in childhood or youth with swelling especially of the lips [Zygidakis et al, 19791.

However, in the M-R syndrome, mental retardation, sensorineural deafness, and skeletal changes, as present in the sibs described by Fountain and the 2 brothers of this report, have never been documented.

In addition to the triad of mental retardation-sensorineural deafness-facial ple- thorism, the third, isolated, patient of this report had the same short and plump hands as found in the 2 brothers. Epileptic attacks never occurred in this male, but there was short stature, and motor impairment was more severe than in the other patients.

From the present observations it appears that, in addition to the diagnostic triad, this apparently autosomal recessive syndrome may be associated with a variety of additional major and minor abnormalities. These can only be further delineated by detailed description and documentation of additional patients.

REFERENCES

Fountain RB (1974): Familial bone abnormalities, deaf mutism, mental retardation, and skin granulomas.

Zygidakis C, Tsankanikas C, Hias A, Vassilopoulos D (1979): Melkersson-Rosenthal’s syndrome in Proc R Soc Med 67:878-879.

four generations. Clin Genet 15:189-192.

Edited by John M. Opitz and James F. Reynolds